Bridging bioceramics and advanced 2D/porous materials: a review of hydroxyapatite/metal–organic framework and hydroxyapatite/MXene composites

Abstract

Hydroxyapatite (HAp) is a well-known bioceramic material with excellent biocompatibility, bioactivity, and chemical stability. However, its brittleness, low surface reactivity, and limited functionality restrict its use in advanced applications such as drug delivery, catalysis, and sensing. To overcome these limitations, HAp has recently been combined with metal–organic frameworks (MOFs) and MXenes, two emerging classes of functional materials. MOFs provide high surface area and tunable porosity, whereas MXenes offer excellent electrical conductivity and photothermal properties. In turn, HAp enhances the structural stability of these materials by improving the moisture resistance of MOFs and reducing the restacking tendency of MXenes. In both types of composites, HAp primarily acts as a bioactive and ion-rich support, while the MOF or MXene component provides the desired functional properties. This common design strategy forms the basis of the present review, which is the first to comparatively discuss HAp/MOF and HAp/MXene composites within a single framework. The review summarizes their synthesis methods and applications in biomedical engineering, environmental remediation, catalysis, electrochemical sensing, coatings, and agriculture. More importantly, it critically examines whether the reported performance improvements arise from true synergistic interactions or simply from the individual contributions of each component. It also compares the reproducibility of different fabrication strategies, discusses the distinct mechanisms through which HAp improves the stability of MOFs and MXenes, and evaluates the maturity of reported applications based on real-sample testing and in vivo validation. Finally, a comparative summary is provided covering the role of HAp, synthesis strategies, interfacial interactions, advantages, limitations, applications, and current research challenges. This review provides a comprehensive reference for researchers interested in the design and development of HAp-based hybrid composites.

Integration of hydroxyapatite with MOFs and MXenes synergistically enhances their properties for superior performance in multifunctional applications.

1. Introduction

Composite materials play a crucial role in modern materials science since they involve the combination of distinct constituents to impart properties that are not attainable by single-component systems.¹ By carefully designing composites, it is possible to enhance mechanical strength, chemical stability, surface functionality, and multifunctional performance. These properties are essential for versatile applications that range from biomedicine to energy and environmental technologies.²

Among various ceramic materials that were explored for such hybridization, hydroxyapatite (HAp) occupies a predominantly important position. HAp is a calcium phosphate ceramic with a chemical composition similar to natural bone mineral, and it has attracted substantial interest owing to its excellent biocompatibility, bioactivity, osteoconductivity, and environmental friendliness.^3,4 Despite these advantages, pristine HAp has several limitations that are intrinsic to it. They include brittleness, low fracture toughness, limited surface reactivity, and poor functional tunability. These drawbacks restrict HAp's performance in advanced applications such as controlled drug delivery, catalysis, sensing, and electrochemical devices.^5,6 This gap between HAp's offering and required demands needs to be filled, and this is the main focus of this review. This precise gap has driven researchers toward integrating HAp with advanced functional materials that are capable of compensating for its weaknesses while preserving its biological and chemical advantages.⁷

Two such materials, both undergoing rapid independent growth in materials science literature, are metal–organic frameworks (MOFs) and MXenes. MOFs belong to the class of crystalline porous materials that are constructed from metal ions or clusters, coordinated with organic ligands.⁸ They are well-known for their high surface area, tunable pore size, adjustable chemical functionality, and structural diversity. These features make MOFs highly attractive for applications in gas storage, separation, catalysis, drug delivery, sensing, and environmental remediation.⁹ However, many MOFs exhibit limited mechanical stability and moisture sensitivity, which can limit their practical use.

MXenes are a rapidly growing family of two-dimensional transition-metal carbides and nitrides. They also have emerged as an important class of advanced materials. MXenes are typically represented by the general formula M_n+1X_nT_x. They exhibit high electrical conductivity, hydrophilicity, rich surface terminations (–O, –OH, –F), and strong photothermal and electrochemical properties.¹⁰ These features allow them to be used in energy storage, electromagnetic shielding, sensors, catalysis, and biomedical applications.¹¹ However, MXenes are vulnerable to oxidation and restacking, which can reduce their performance.¹² Combining MXenes with HAp provides structural stabilization, improved dispersion, and enhanced biocompatibility.

The reason behind considering functionalization of HAp with MOFs and MXenes is that their respective strengths and weaknesses align in a complementary manner. HAp's biological stability and ion-exchange capability can help anchor and stabilize the relatively fragile MOF and MXene frameworks, while the high surface area, tunable porosity, electrical conductivity, and photothermal behavior of MOFs and MXenes directly compensate for HAp's brittleness, low reactivity, and limited functional versatility. In other words, hybridizing HAp with MOFs or MXenes is not simply an additive combination of properties, but a synergistic relationship in which each material overcomes the limitations of the other. HAp consistently exerts the role of a bioactive, ion-rich, and interfacially active scaffold in both composite families. On the other hand, MOFs and MXenes act as the interchangeable functional partner by contributing with porosity and tunable surface chemistry (features of MOFs), or electrical conductivity, photothermal response, and metallic surface terminations (features of MXenes). It is this shared scaffold-plus-function design logic, rather than any structural resemblance between MOFs and MXenes themselves, that justifies treating HAp/MOF and HAp/MXene composites within a single, unified review. In current research community, this complementary relationship is widely accepted and adopted. Over the past few years, works are being reported on HAp/MOF and HAp/MXene composites for biomedical, catalytic, environmental, and electrochemical applications.^13–18

A lot of reviews exist that report research works on MOF-based composites,¹⁹ MXene-based composites,²⁰ and composites combining MOFs with MXenes.²¹ However, a dedicated review that brings both HAp/MOF and HAp/MXene composites together within a single, unified framework is currently missing from the literature. From our viewpoint, this is a significant gap as both material combination is originated from the same core motivation, which is enhancement of HAp's functional versatility with simultaneous improved stability of MOFs and MXenes. Bringing both composite families together allowed to provide a direct comparison of their synthesis strategies, fortification approaches, and application performance. Additionally, it also aided in creating a more complete picture of the evolvement of HAp-based hybridization. In view of this, the present review aims to serve as a single, consolidated reference that introduces readers to the fundamentals of HAp, MOFs, and MXenes, and systematically organizes the current state of knowledge on HAp/MOF and HAp/MXene composites, thereby supporting both newcomers and experienced researchers working in this emerging area of materials science.

2. Overview of hydroxyapatite

The name “hydroxyapatite” derives from the Greek word “apatite”, which means “to mislead” or “to deceive” because it had previously been mistaken for other minerals (i.e., beryl, tourmaline, fluorite, etc.) and the word also consists of “hydroxy,” which denotes the presence of hydroxyl (OH) groups in its structure.^22,23 Calcium hydroxyapatite is commonly referred to as hydroxyapatite (HAp) that has similarity with the mineral constituents of human bone and teeth. It is usually represented by the chemical formula Ca₁₀(PO₄)₆(OH)₂ with Ca/P stoichiometric ratio of 1.67.^24,25 Structurally, HAp typically has hexagonal (space group P6₃/m) or monoclinic (space group P2₁/b) crystal structure (Fig. 1) where the lattice core is formed mainly by Ca²⁺, PO₄³⁻, and OH⁻ in a 3D network.^23,26 The substitution of Ca²⁺ site in HAp with monovalent/divalent ions and the phosphate/hydroxyl group site by ions such as F⁻, Cl⁻, CO₃²⁻ causes improvement of properties as crystallinity, solubility, bioactivity, modifying HAp, etc.^27,28 Bone consists of approximately 70% HAp, 20% collagen, and 10% water, whereas tooth enamel is composed of about 97% HAp with only 3% organic materials and water.^14,15 Biological apatite is non-stoichiometric and nanocrystalline, unlike pure HAp, contains important minor substituents (CO₃²⁻, Na⁺, Mg²⁺, etc.), and it is more accurately described as carbonated apatite or carbonate apatite.^29,30 HAp exhibits slight solubility in water and neutral pH, yet readily dissolves in acidic environments.³¹ Pure synthetic HAp is white in color, but biogenic and mineral HAp are different in color (such as off white, gray, green, brown, etc.) due to the presence of impurities like iron or manganese.³²

Fig. 1. (a) Hexagonal and (b) monoclinic crystal structures of HAp.

2.1. Sources of HAp

Primarily, HAp can be sourced from natural and synthetic sources. Natural HAp is sourced from biological sources or wastes such as mammalian bone (bovine, camel, horse, etc.), marine or aquatic sources (fish bone, fish scale, fish teeth, coral, etc.), shell sources (cockle, oyster, clam, eggshell, seashell, etc.), plant sources (red algae), and also from mineral sources (limestone).^33–37 The synthetic HAp is produced from different chemical precursors like calcium carbonate, calcium hydroxide, or calcium nitrate, reacting with phosphate sources, such as diammonium hydrogen phosphate or phosphoric acid.³³Fig. 2 illustrates the natural sources of HAp, whereas Table 1 lists the key differences between natural and synthetic HAp.

Fig. 2. Natural sources of hydroxyapatite.

Table 1. Comparison between natural and synthetic sourced HAp.

Aspect	Natural HAp	Synthetic HAp	Ref.
Source	Mammalian bone, marine or aquatic sources, shell sources, plant sources, mineral sources, etc.	Ca precursors such CaCO3, Ca(OH)2, Ca2P2O7, etc., and P precursors such as Na2HPO4, K2HPO4, etc.	33
Cost	Economical and low processing cost due to the availability	More expensive due to the advanced equipment, highly pure reagents, and energy-intensive process	36
Ca/P ratio	The non-stochiometric ratio is not exactly 1.67 due to the natural variation of components	Stochiometric at exactly 1.67	38
Trace element	Contains Mg, Na, K, Zn, Sr, Fe, Si,etc.	Trace elements are absent unless doped	35
Processing time	Generally faster	Generally slower	35
Sustainability	Sustainable due to the use of waste and, reduction of pollution	Less sustainable due to the use of chemicals and energy consumption	39

2.2. Synthesis methods of hydroxyapatite (HAp)

HAp has been synthesized using a wide range of approaches including dry, wet chemical, high-temperature, hybrid, biogenic, and assisted methods. Each technique offers distinct advantages in terms of particle morphology, crystallinity, purity, scalability, and processing cost. Table 2 summarizes the basic principles, key characteristics, representative examples, and references for the most commonly employed HAp synthesis methods.

Table 2. Summary of common synthesis methods for HAp.

Synthesis method	Basic principle	Key features	Representative examples	Ref.
Solid-state	- Mix solid Ca and P precursors	Simple, inexpensive, scalable; high crystallinity but limited control over particle morphology	Ca(NO3)2·4H2O/(NH4)2HPO4/NaHCO3; eggshell-derived HAp via calcination	40–42
	- Calcination at high temperature
Mechanochemical	- High-energy ball milling	Solvent-free or minimal solvent; efficient mixing; waste-derived synthesis possible	Ball milling of CaCO3/Ca2P2O7; eggshell-derived CaO	23, 43 and 44–46
	- Optional annealing
Hydrothermal	- Reaction in sealed autoclave	High crystallinity; controlled crystal growth; good morphology control	Ca(NO3)2 with (NH4)2HPO4; CaHPO4·2H2O/Ca(OH)2	47–49
	- High temperature and pressure
Sol–gel	- Sol formation	High purity; homogeneous composition; nanosized particles	Calcium nitrate/P2O5; triethyl phosphite hydrolysis	50–52
	- Gelation
	- Calcination
Chemical precipitation	- Controlled precipitation in aqueous solution	Simple, low-cost, scalable; morphology depends on pH, temperature and Ca/P ratio	Ca(NO3)2·4H2O with (NH4)2HPO4 under alkaline conditions	53–56
	- pH adjustment
Sonochemical	- Ultrasonic cavitation	Rapid nucleation; uniform nanoparticles; short reaction time	Ultrasonic synthesis in latex; various calcium/phosphate precursors	57 and 58–60
	- Localized high temperature and pressure
Emulsion	- Microemulsion confines nucleation	Good control of particle size and morphology	Cyclohexane-based microemulsion; W/O/W emulsion	61 and 62
	- Surfactant-assisted growth
Hydrolysis	Hydrolysis of calcium phosphate precursors	Produces non-stoichiometric HAp; often combined with hydrothermal treatment	CaHPO4·2H2O/CaCO3 in alkaline medium	63 and 64
Solvothermal	Solvothermal reaction in organic solvent	Tailored morphology; anisotropic crystal growth	HAp nanowires from calcium nitrate/phosphoric acid	65 and 66
Pyrolysis (spray pyrolysis)	Thermal decomposition of aerosol droplets	Continuous production; scalable; high-temperature processing	Ultrasonic spray pyrolysis up to 1000 °C	67 and 68
Hybrid methods	Combination of two or more synthesis techniques	Improved control of crystallinity, morphology and purity	Mechanochemical-hydrothermal; hydrothermal-microemulsion; hydrothermal-hydrolysis	69–71
Biogenic source-derived	Conversion of natural Ca-rich wastes into HAp	Sustainable; low-cost; supports waste valorization	Fish scales, bones, eggshells, oyster shells	3, 34, 36 and 72–74
Microwave-assisted	Microwave dielectric heating	Very short reaction time; energy-efficient; high yield	Microwave synthesis completed within ∼30 min	57 and 75–77
UV-assisted	UV irradiation promotes reaction	Reduced reaction time; improved purity	Eggshell-derived HAp under UV irradiation	24

2.3. Application of hydroxyapatite

Due to its biocompatibility, biodegradability, bioactivity, nontoxicity, and noninflammatory characteristics and similarity to biological minerals, HAp is widely used in biomedical applications like bone grafts, implants, tissue engineering, dental applications, coating for orthopedic implants, etc.³⁴ Nano-sized HAp facilitate drug delivery since its porous structure and high surface area promote efficient drug loading.^28,40,78 It also has applications in environmental remediation as an adsorbent as it effectively adsorbs heavy metals, dyes, pollutants, etc., from water.^40,79 It also promotes catalytic and sensor applications due to its unique properties.^80,81 The versatility of HAp makes it a key material in research and applied sciences. Fig. 3 summarizes the key fields of applications of HAp.

Fig. 3. Schematic diagram of applications of HAp. Partly generated with Google Gemini.

3. Overview of metal–organic framework (MOF)

Metal–organic framework (MOF) is a 3D crystalline porous material which are formed by the combination of metal ion (Zn²⁺, Cu²⁺, Fe³⁺etc.) and organic linker. The metal units act as nodes, while the organic molecules act as bridges. These components connect through coordination bonds to form ordered three-dimensional networks. The structure of a MOF can be tuned by changing the metal, the linker, or both. It was first reported by scientist Omar Yaghi at UC Berkeley by mixing two components (zinc nitrate and 1,4-benzene di-carboxylic acid) in N,N-dimethylformamide and formed MOF-5 complex ([Zn₄O(BDC)₃]).⁸² MOF generally shows different structures such as triangular, octahedral, triangular prism like, square paddle like shape.⁸³ Nowadays, MOF has versatile applications due to their excellent photocatalytic activity, large surface area, high porosity, adjustable pore size, arranged structure, resistant to metal volume, and tunable properties.⁸⁴ MOFs can be prepared by different types of method such as hydrothermal, slow diffusion, electrochemical, mechanochemical, sonochemical, and microwave assisted heating, etc. Iso-reticular MOFs (IRMOFs), zeolite imidazole frameworks (ZIFs), coordination polymers (PCPs), porous coordination network (PCNs), and Materials Institute Lavoisier (MILs) are widely studied classes of MOFs.⁸⁵ MOFs are used in gas separation, wastewater treatment, photochemical and electrochemical sensing, medical imaging, drug delivery, separation and purification technologies.⁸⁶

3.1. Classification of MOFs

MOFs are commonly classified based on their structural building units and framework topology. This includes the type of metal node, nature of organic linker and the resulting pore structure.⁸⁶ Below are the types of MOFs that are classified on the above mentioned basis.

3.1.1. Iso-reticular MOFs (IRMOFs)

IRMOFs use zinc oxide clusters as metal nodes which are connected by aromatic carboxylate linkers. They form octahedral cages with high surface areas. Their structures can be expanded by changing linker lengths without altering the basic topology. They are mainly synthesized by solvothermal methods at room temperature to avoid overlapping networks. They show superior performance in gas storage due to large pores and tunable sizes. Their applications include sensing explosives and separation of noble gases.⁸³

3.1.2. Zeolite imidazole frameworks (ZIFs)

ZIFs are synthesized by linking metals like zinc or cobalt with imidazole groups to mimic zeolite structures. They are of tetrahedral unit structures with stable hydrophobic pores. They are typically synthesized by simple aqueous or microwave methods for quick formation of the nanocrystals. ZIFs can resist water and heat very well. They are used in gas separation, pH sensitive drug delivery, and metal ion sensing.⁸⁶

3.1.3. Materials of Institute Lavoisier (MIL) MOFs

Materials Institute Lavoisier (MIL) are formed by the combination of trivalent metal ion like Cr³⁺, Fe³⁺, Al³⁺etc. with organic linkers like polycarboxylates. They are widely known for strong metal–ligand bonding and good thermal stability. Many MILs contain large pores and flexible frameworks. Because of their stability and biocompatibility, MILs are studied for drug delivery, adsorption, and catalysis.⁸⁷

3.1.4. Porous coordination network (PCNs)

PCNs are three-dimensional MOFs which are designed with rigid metal clusters and multitopic organic linkers that creates an internal structure of interconnected cages and openings. PCNs exhibits high surface area, tunable pore size, chemical and thermal stability. PCNs are widely studied for gas storage, especially hydrogen and carbon dioxide. Their structures can be tailored by changing linker geometry, which helps in controlling pore size and adsorption behavior.⁸⁶

3.1.5. University of Oslo (UiO) MOFs

UiO MOFs are a well-known family of MOFs that are based on zirconium or hafnium metal clusters and dicarboxylate organic linkers. The name UiO comes from the University of Oslo, Norway. The first UiO-type MOF, UiO-66, was developed by researchers in 2008 working at this university. To acknowledge the place of discovery, the framework was named after the institution. UiO MOFs have a strong Zr–O bond, which makes them resistant to water, acids, and many other solvents. Because of this stability, UiO MOFs are widely studied for gas adsorption, catalysis, drug delivery, and environmental remediation.⁸⁸

3.1.6. HKUSTs (Hong Kong University of Science and Technology MOFs)

HKUST MOFs are based mainly on copper metal ions and benzene-1,3,5-tricarboxylate (BTC) organic linkers. The most famous member is HKUST-1, also called Cu-BTC. Its structure contains paddle-wheel Cu₂(COO)₄ secondary building units that form a three-dimensional porous network.⁸⁹

Based on this classification approach like UiOs and HKUSTs, several distinct MOF families have been developed and reported in recent years. Some of them are Northwestern University (NU series), Pohang University of Science and Technology (POST series), Dresden University of Technology (DUT series), the University of Nottingham (NOTT series), and Christian-Albrechts-University (CAU series).⁸³ Crystal structure of the six MOF major types are presented in Fig. 4.

Fig. 4. Crystal structures of different types of MOF. The structures were made by VESTA.

3.2. Naming metal–organic frameworks

Since MOFs are relatively a new class of materials, a single universally accepted naming system has not yet been established. As a result, different approaches are seen to be used while naming MOFs. One common approach is sequential numbering, where frameworks are labeled in the order they were discovered or synthesized. For example, MOF-2, MOF-3, MOF-5, etc. Another widely used method is institution-based naming, in which MOFs are named using abbreviations of the university or research center where they were first reported. For example, HKUST-n or UiO-66. A third approach relies on isoreticular design, where MOFs with the same topology but different linker lengths are grouped under the IRMOF series. In some cases, MOFs are also identified by their chemical formula, showing the metal nodes, organic linkers, and their stoichiometric ratios.⁹⁰Table 3 lists the different MOFs, their structure and the basis of their nomenclature.

Table 3. Different MOFs and their basis of terminology.

Terminology	Full name	Chemical composition	Metal unit	Organic linker	Why it is termed so	Ref.
MOF-2	Metal–organic framework-2	Zn(BDC)(H2O)	Zn	BDCa	Earliest metal–organic framework reported by Omar Yaghi. Numbered sequentially as MOF-2 in their series of coordination polymers	91 and 92
MOF-5	Metal–organic framework-5	[Zn4O(BDC)3]	Zn	BDCa	5th MOF structure reported by Omar Yaghi	93
MOF-177	Metal–organic framework-177	[Zn4O(BTB)6]	Zn	BTBb	177 as a sequential lab identifier reported in 2004	94
UiO-66	University of Oslo-66	[Zr6O4(OH)4(BDC)6]	Zr	BDCa	The numbers (66, 67, 68) serve as sequential identifiers in the UiO series. UiO-66 uses the shortest linker, UiO-67 uses a longer biphenyl-based linker and UiO-68 uses the longest terphenyl-based linker	88
UiO-67	University of Oslo-67	[Zr6O4(OH)4(BPDC)6]	Zr	BPDCc
UiO-68	University of Oslo-68	[Zr6O4(OH)4(TPDC)6]	Zr	TPDCd
IRMOF-1	Iso-reticular metal–organic framework-1	[Zn4O(BDC)3]	Zn	BDCa	First in the IRMOF series developed by Omar Yaghi's group, emphasizing expandable structures with the same topology as MOF-5 but varying linker lengths or functionalities	92
IRMOF-3	Iso-reticular metal–organic framework-3	[Zn4O(NH2-BDC)3]	Zn	NH2-BDCe	Third in the IRMOF series	95
ZIF-8	Zeolite imidazole framework-8	Zn(mIm)2	Zn	mImf	Number 8 refers to its specific sodalite (SOD) zeolite-like topology	96 and 97
ZIF-10	Zeolite imidazole framework-10	Zn(Im)2	Zn	Img	Number 10 denotes its rho (RHO) topology with unsubstituted imidazolate linkers
MIL-53	Materials of Institute Lavoisier-53	M(OH)(BDC)·xH2O	M = Al, Cr, or Fe	BDCa	Developed at the Materials Institute Lavoisier, 53 is a sequential identifier for this flexible, breathing framework	98
MIL-88	Materials Institute Lavoisier-88	M3O(BDC)3·xH2O	M = Fe or Cr	BDCa	88 indicate synthesis sequence in MIL
HKUST-1(MOF-199)	Hong Kong University of Science and Technology	Cu3(BTC)2	Fe2+, Pd2+, Cd2+, Ni2+	BTCh	From the university of Hong Kong science and technology, first in their series	99

^a1,4-Benzene-dicarboxylate.

^b1,3,5-Benzenetribenzoate.

^c4,4′-Biphenyl-dicarboxylate.

^dTerphenyl dicarboxylate.

^e2-Amino-1,4-benzenedicarboxylate.

^f2-Methylimidazolate.

^gImidazolate.

^h1,3,5-Benzene tricarboxylic acid.

3.3. Synthesis methods of MOFs

Various synthesis routes have been developed to synthesize MOFs such as solvothermal, microwave-assisted, hydrothermal, mechanochemical, sonochemical, and electrochemical, etc. These methods are briefly listed in the following Table 4 and the methodologies are illustrated in Fig. 5.

Table 4. Summary of common synthesis methods for MOFs.

Synthesis method	Basic principle	Key features	Representative examples	Ref.
Solvothermal	- Metal salts and organic linkers dissolved in organic or mixed solvents	Most widely used method; high crystallinity and yield; particle size and morphology controlled by temperature, solvent, concentration, and reaction time	HKUST-1, ZIFs, UiO, MIL series synthesized in DMF, DEF, ethanol, methanol or mixed solvents	100 and 101
	- Sealed vessel reaction at elevated temperature and pressure
Hydrothermal	- Similar to solvothermal synthesis	Environmentally friendly; good crystallinity; suitable for water-stable MOFs; crystal growth controlled by temperature, pH and metal-to-ligand ratio	Zn2+ or Cr3+ salts with BTC, BTB or BDC linkers	102
	- Water used as the reaction solvent in a sealed autoclave
Microwave-assisted	- Microwave dielectric heating of precursor solution	Very short synthesis time; improved crystallinity; energy-efficient; uniform particle size	Microwave-assisted synthesis of HKUST-1, ZIFs and other MOFs	102 and 103
	- Rapid and homogeneous heating
Mechanochemical	- Grinding or ball milling of metal salts and organic linkers	Solvent-free or minimal solvent; environmentally friendly; low energy consumption; rapid synthesis	Ball milling or mortar grinding of metal salts with organic ligands	104 and 105
	- Optional liquid-assisted grinding
Electrochemical	- Metal ions generated by anodic dissolution	High-purity products; avoids counter-ion contamination; controlled crystal growth; suitable for continuous production	Industrial synthesis of HKUST-1 by anodic dissolution	102 and 106
	- Coordination with dissolved organic ligands
Sonochemical	- Ultrasonic irradiation induces acoustic cavitation	Fast reaction; environmentally friendly; high-purity crystals; particle size and morphology controlled by sonication conditions	Ultrasonic synthesis using metal salts and organic ligands in solution	107
	- Localized high temperature and pressure promote nucleation

Fig. 5. Synthesis methodologies of MOF: (a) solvothermal, (b) micro-wave-assisted, (c) mechanochemical, (d) electrochemical, (e) sonochemical and (f) hydrothermal methods. Partly generated with Google Gemini.

3.4. Application of MOFs

MOFs have been extensively investigated for applications in gas storage, biomedicine, electrochemistry, wastewater treatment, and sensing owing to their exceptionally high surface area, tunable porosity, and versatile chemical functionality.¹⁰⁸ In gas storage, their porous framework enables efficient adsorption of hydrogen, methane, CO₂, and nitrogen, with storage performance strongly influenced by pressure and temperature.^109–112 In the biomedical field, MOFs serve as stimuli-responsive drug delivery systems and have also been explored for disease diagnosis, tissue engineering, detoxification, and gas delivery, with materials such as ZIF-8, UiO-66-NH₂, MIL-100(Fe), IRMOF-3, and β-cyclodextrin MOFs successfully employed for therapeutic agent delivery.^83,113–115 Their high surface area, tunable pore structure, and redox-active metal centers also make MOFs attractive for electrochemical applications including lithium-ion batteries, supercapacitors, sensors, corrosion protection, and CO₂ electrocatalysis.^83,116,117 In wastewater treatment, MOFs efficiently remove organic and inorganic contaminants through adsorption and membrane separation and also act as catalysts in advanced oxidation processes such as photocatalysis and Fenton reactions.^118–121 Furthermore, their structural diversity, luminescence, and selective adsorption properties have enabled the development of optical and electrochemical sensors for gases, heavy metals, antibiotics, pesticides, pathogens, and disease biomarkers, with applications in environmental monitoring, food safety, and biomedical diagnostics.^122,123 Major applications of MOFs have been illustrated in Fig. 6.

Fig. 6. Applications of metal–organic frameworks in various fields like sensing, gas storage, wastewater treatment, electrochemical and biomedical applications. Generated with Google Gemini.

4. Overview of MXene

MXenes, with a 2D structure, represent a rapidly promising group that can be defined as two-dimensional metal carbide or nitride.¹²⁴ They are well known for their exceptional electrical conductivity, mechanical strength, hydrophilicity, high bulk energy density, optical band gap, carrier mobilities, thermal conductivity and tunable surface chemistry. Such properties enables them to be used in energy storage devices, sensors, dye degradation and catalysis.¹²⁵ Michael Naguib et al. at Drexel University first reported MXene in their work.¹²⁶ They synthesized MXene by selectively etching aluminum layers from Ti₃AlC₂ (MAX phase) and marked the breakthrough in 2D material synthesis beyond graphene.

The general formula of MXenes is M_n+1X_nT_x, where M is an early transition metal such as (Ti, V, Nb, Mo, Cr etc.), X is either carbon or nitrogen, and T represents surface termination groups for example-oxygen (O), fluorine (F), hydroxyl (OH) or chlorine (Cl).^127,128 The parent group from which MXenes are obtained is MAX phase, where A is an element of group 13 or 14 like Al, Si, Ge, Ga, and the general formula is M_n+1AX_n.^127,129 MAX phase can be obtained by various methods including isostatic pressing, self-propagating high-temperature synthesis, spark plasma sintering, ball milling and others.¹³⁰ The bond between M–X is stronger than M–A bonds, therefore, A layer is etched using a mixture of LiF and HCl and delaminated to obtain single or few layered structure.¹²⁷ In order to delaminate, dimethyl sulfoxide (DMSO), tetramethylammonium hydroxide (TMAOH), lithium chloride (LiCl) or other intercalants can be used, but they can remain on the surface of MXene flakes after washing.¹³⁰ The preparation of MXene by selective etching of Al-layer is categorized as a top-down approach and it is presented in Fig. 7. In addition, SEM images of MAX phase before and after etching is shown in Fig. 8.

Fig. 7. Preparation of MXene from MAX phase by etching the Al layer: (A) HF treatment to produce MXene with a multilayered structure, followed by delamination to get few-layered MXene sheets, and (B) Al layer is eliminated by etching followed by exfoliation to get MXene sheets. Reproduced under the terms of the CC BY 4.0 license.¹³¹ Copyright 2024, the author(s), published by Elsevier B.V.

Fig. 8. SEM images of (a) Ti₃AlC₂ and after HF treatment for (b) 2 h, (c) 10 h, (d) 20 h. Reproduced with permission.¹³² Copyright 2016, Elsevier Ltd.

4.1. Classification of MXenes

In a broader context, MXenes can be classified into three main categories: mono transition metal MXenes, double transition-metal (DTM) MXenes, and divacancy MXenes (Fig. 9). Mono transition metal MXenes consist of only one type of transition metal element in their structure. Typical examples include Ti₂CT_x, V₂CT_x, Ti₃C₂T_x, and Nb₄C₃T_x.¹³³

Fig. 9. Classification of MXenes based on transition metal element.

Double transition-metal (DTM) MXenes are composed of two different transition metals, commonly denoted as M′ and M″. These MXenes are further divided into ordered DTM MXenes and solid-solution MXenes. Ordered DTM MXenes are classified based on the arrangement of transition metals within the M layers into in-plane ordered and out-of-plane ordered structures. In in-plane ordered MXenes, two different transition metals occupy alternating sites within the same atomic plane, with a general formula of . In contrast, out-of-plane ordered MXenes contain transition metals in separate atomic planes, where M″ occupies the inner layers and M′ forms the outer layers, resulting in structures with general formulas .¹³⁴ In solid-solution DTM MXenes, the transition metals are randomly distributed throughout all M layers. These materials follow the general formula (M′,M″)_n+1C_nT_x, with examples including (Ti,V)₂CT_x, (Ti,Nb)₃C₂T_x, and (Nb,Zr)₃C₂T_x.^135,136

Divacancy MXenes are formed when the etching process removes both the “A” element and a fraction of the “M” element. Such way an ordered metal vacancies within the structure is created. Mo_1.33C MXene is a representative example of this class and exhibits high electrical conductivity. This material has been reported to show approximately 65% higher volumetric capacitance, reaching around 1100 F cm⁻³.¹³⁷

4.2. Synthesis methods of MXenes

The synthesis of MXenes generally involves two key steps: preparation of the MAX phase precursor, followed by selective etching of the “A” layer to obtain MXene sheets.

4.2.1. Synthesis of MAX phase

The quality of the MAX phase strongly influences the structural and chemical properties of the resulting MXenes. Therefore, MAX phases with controlled stoichiometry, high crystallinity, and low oxygen content are preferred. Simultaneously, Al-rich MAX phases can further improve the environmental stability of the derived MXenes. Several synthesis routes have been developed, including solid-state reaction, molten salt synthesis, self-propagating high-temperature synthesis, electrolysis, hot pressing, hot isostatic pressing, and spark plasma sintering.^130,138

Among these, the solid-state reaction is the most widely used method, where elemental powders are mixed and sintered under an inert atmosphere to produce crystalline MAX phases.¹³⁰ The molten salt method utilizes inert molten salts to enhance reactant diffusion, enabling MAX phase formation at lower temperatures and shorter reaction times.¹³⁹ An alternative approach is electrochemical synthesis, where oxide precursors are electrolyzed in molten salts to produce MAX phases using inexpensive starting materials while avoiding extreme processing conditions.¹³⁸ Graphical illustrations of these synthesis methods are presented in Fig. 10.

Fig. 10. Synthesis methods of MAX phase: (a) solid phase reaction method, (b) molten salt method, and (c) electrolysis method. Partly generated with Google Gemini.

4.2.2. Synthesis of MXenes via etching of MAX phases

MXenes are primarily synthesized by selectively removing the “A” layer from MAX phases. This can be achieved through top-down or bottom-up approaches. Fig. 11 illustrates the synthesis of MXenes via etching of MAX Phases.

Fig. 11. Synthesis methods of MXenes via etching of MAX phases: top-down approaches: (a) wet chemical etching, (b) Lewis acid etching, and (c) hydrothermal method; bottom-up approaches: (d) chemical vapor deposition method, (e) plasma enhanced pulsed laser deposition, and (f) template method. Partly generated with Google Gemini.

In the top-down route, pre-synthesized MAX phases are chemically etched, whereas the bottom-up approach directly constructs MXene layers from elemental or molecular precursors. The top-down approach is the most widely used method for MXene synthesis. In this method, the structure and composition of bulk layered carbide or nitride MAX phase precursors are selectively modified to obtain two-dimensional MXenes such as T₃C₂T_x or Ti₃N₂T_x.¹⁴⁰ Common top-down etching methods include wet chemical etching, Lewis acid etching, hydrothermal etching, and electrochemical etching.

Wet chemical etching is a conventional method, in which hydrofluoric acid (HF) or an in situ generated HF system (e.g., LiF + HCl) is used as the etchant. During etching, the “A” layer (typically Al) is selectively removed that results in a multilayered MXenes containing terminated surface functional groups (such as –F, –OH, and –O). Although it is simple and suitable for large-scale production, the use of fluoride-containing reagents raises significant safety and environmental concerns.¹²⁸

To overcome these limitations, Lewis acid etching has emerged as a fluoride-free alternative that employs molten salts such as ZnCl₂, CuCl₂ or NaCl, to remove the “A” layer while simultaneously introducing new surface terminations. Despite its environmental benefits, this method requires elevated temperatures and more complex processing.^141,142

Electrochemical etching offers a greener route by selectively removing the “A” layer under an applied potential. This allows better control over surface chemistry and facilitating delamination. However, excessive applied voltage may generate amorphous carbon, making process optimization essential.¹⁴³

In hydrothermal etching, alkaline solutions or mild fluoride-containing reagents are used under hydrothermal conditions to selectively dissolve the “A” layer. The quality of the resulting MXenes depends strongly on the etchant concentration, reaction temperature, and duration.^144,145

Bottom-up synthesis directly forms MXenes from elemental or molecular precursors instead of using MAX phases. Representative methods include chemical vapor deposition (CVD), plasma-enhanced pulsed laser deposition (PEPLD), and template-assisted synthesis.¹⁴⁶ Although these approaches can produce highly crystalline and defect-controlled ultrathin MXene films, they generally yield thin films rather than free-standing single-layer MXenes and require more sophisticated processing than top-down methods.^{142,147–150}

Following etching, MXenes usually remain in a multilayered form due to strong interlayer van der Waals interactions and hydrogen bonding. Therefore, a delamination step is required to obtain few-layer or single-layer nanosheets.^130,151 Sonication alone often provides limited exfoliation efficiency, so liquid-phase exfoliation using intercalating agents such as DMSO, TMAOH, TBAOH, or LiCl is commonly employed to expand the interlayer spacing and weaken interlayer interactions.^124,147,151 For MXenes synthesized by LiF/HCl etching, intercalation is often facilitated by Li⁺ ions, reducing the need for additional intercalants.¹²⁸ Nevertheless, complete removal of residual intercalating species remains challenging and may influence the surface chemistry and performance of the final MXenes.

4.3. Applications of MXenes

MXenes, particularly Ti₃C₂T_x, have attracted significant attention owing to their high surface area, metallic conductivity, hydrophilicity, and tunable surface terminations, enabling applications in energy storage, environmental remediation, biomedicine, sensing, and catalysis. In energy storage, their excellent electrical conductivity, pseudocapacitance, and expanded interlayer spacing facilitate ion intercalation, resulting in high electrochemical performance. Naguib et al.¹⁵² first demonstrated Ti₃C₂T_x as a lithium-ion battery electrode with a specific capacity of 225 mAh g⁻¹, nearly five times higher than its parent MAX phase.^153,154 In environmental remediation, MXenes act as efficient adsorbents for pollutants due to their layered structure, large surface area, and negatively charged surfaces, with Ti₃C₂T_x exhibiting high adsorption capacity toward methylene blue.^155–157 In biomedicine, their large surface area and tunable surface chemistry enable drug delivery, biosensing, bioimaging, antibacterial activity, and photothermal cancer therapy, including high doxorubicin loading with stimuli-responsive release.^151,158,159 MXenes are also widely employed in electrochemical, gas, and biosensors because of their high conductivity and abundant surface functional groups, making them suitable for clinical diagnostics, food safety, and environmental monitoring.^159–161 Furthermore, their high electrical conductivity, hydrophilicity, tunable surface chemistry, and abundant active sites make MXenes promising electrocatalysts for hydrogen evolution, oxygen evolution, and oxygen reduction reactions, providing a cost-effective alternative to noble-metal catalysts for renewable energy applications.^{138,162–164}Fig. 12 illustrates the versatile applications of MXenes.

Fig. 12. Multifunctional applications of MXenes. Generated with Google Gemini.

4.4. Challenges associated with MXenes application

Despite their exceptional properties, several challenges limit the large-scale and long-term application of MXenes. Key concerns include oxidation instability in aqueous environments, limited scalability of synthesis routes, environmental and safety issues, and potential toxicity in biomedical applications.¹³⁸ Addressing these challenges is essential before MXenes can be widely used in practical technologies.

4.4.1. Oxidation instability

MXenes are highly susceptible to oxidation when exposed to aqueous or ambient environments. If exposed, this will lead to the formation of transition metal oxides and carbonaceous residues. As a result, it significantly reduces electrical conductivity as well as electrochemical performance, therefore, their applications as supercapacitors and sensors get restricted.¹³⁸ To mitigate oxidation, several strategies have been utilized, including encapsulation with inert polymers (e.g., PDMS and PMMA), oxide coating, and surface passivation through salinization. These approaches have been shown to improve oxidation resistance while preserving adsorption and functional properties.¹⁶⁵

4.4.2. Challenges in scalable and sustainable production

Although wet chemical and in situ etching methods enable laboratory-scale production of MXenes, challenges related to high cost, safety risks, and reproducibility hinder large-scale manufacturing.¹⁶⁶ The development of green and scalable synthesis routes is therefore crucial to reduce environmental impact and production costs.¹³⁸ Additionally, the use of low-cost precursor materials, optimization of reagent concentrations, and refinement of reaction conditions are necessary to ensure economic feasibility without compromising material performance.¹³⁸

4.4.3. Toxicity concerns in biomedical applications

MXenes have a attracted increasing interest in biomedical applications due to their antibacterial properties and photothermal therapy efficiency.¹⁵⁸ However, studies have reported dose-dependent cytotoxicity and limited stability under physiological conditions. This may restrict their clinical translation.¹⁶⁶ Comprehensive biocompatibility assessments, long-term toxicity studies, and surface modification strategies are required to ensure their safe use in biomedical systems.

4.4.4. Environmental and safety risks

MXenes synthesized using HF or HF-generating etchants pose significant environmental and health hazards due to fluoride toxicity. The risks associated with HF handling can be partially mitigated by taking some measures. For example, using lower acid concentrations, adopting safer fluoride-based alternatives, and enforcing strict laboratory safety measures (proper ventilation and acid-resistant personal protective equipment). Furthermore, the development of fluoride-free etching strategies offers a promising route to minimize environmental impact and improve process safety.¹³⁸

5. Concept of composite material

A composite material is a substance that consists of two or more distinct constituents, typically a matrix (polymer, metal, ceramics, etc.) and reinforcements (fiber, particles, whiskers, etc.). These constituents are combined at the macroscopic or microscopic scale to obtain better properties than individual components. The matrix binds reinforcement and, the reinforcement imparts strength, stiffness, or other desired properties, forming a heterogeneous structure.^167–169 A composite material generally contains ∼5–70 wt% reinforcement to obtain improved mechanical, thermal, or structural properties. The prime difference between composite and doping is that, composites are a multiphase material, while in doping, single-phase materials are intentionally altered by adding minor impurities (<1%) into host materials. This is carried out to promote electrical, optical, or other properties without changing their overall structure.^170,171

The preparation of composite materials is a multi-step process that involves selecting matrix and reinforcement materials (e.g., polymers, ceramics, metals, or inorganic components). The components are prepared and combined through various methods, such as solution mixing, sol–gel synthesis, co-precipitation, hydrothermal treatment, or in situ growth, depending on the desired structure and properties. After mixing and ensuring proper bonding and phase integration, the composite material undergoes drying, curing, calcination, or sintering. Finally, the materials are processed, shaped, and characterized to determine their structure and composition. For the HAp-based hybrid composites discussed in this review, the matrix-reinforcement concept remains the same whether HAp is combined with a MOF or a MXene. In both cases, HAp acts as the main matrix. It provides biocompatibility, offers an ion-rich surface for strong interfacial interactions, and helps control the surface charge and ion-exchange properties of the composite. The second component is added to introduce specific functions. When combined with MOFs, the composite gains a high surface area and stimuli-responsive porosity. In contrast, MXenes contribute high electrical conductivity, photothermal activity, and abundant surface functional groups. As a result, each composite combines the biological advantages of HAp with the unique properties of the reinforcing material. The following sections discuss HAp/MOF and HAp/MXene composites separately using this common framework. This makes it easier to compare their synthesis methods, interfacial interactions, and performance in different applications.

Fig. 13a illustrates the general concept of composite and Fig. 13b illustrates the general process of composite making.

Fig. 13. (a) General concept of composite and (b) general process of composite making.

6. Composites of hydroxyapatite/metal–organic framework (HAp/MOF)

Hydroxyapatite (HAp)/metal–organic framework (MOF) composite is a hybrid material where HAp acts as the matrix or core with MOF as reinforcement or coating. Through this combination, a multifunctional system is created with enhanced porosity, improved surface area, bioactivity, and stimuli-responsiveness. The HAp/MOF composite is typically synthesized using either an in situ growth or post-synthetic impregnation approach. The in situ approach is a one-pot method of preparing HAp/MOF composite, in which MOF is directly grown on the surface of pre-synthesized HAp during synthesis. It ensures strong interfacial bonding and uniform distribution.^15,172,173 In the post-synthetic impregnation approach, pre-synthesized MOF is combined with HAp by physical mixing and a solvent-assisted filling procedure, resulting in a hierarchical structure with improved porosity.^174,175Fig. 14 shows the generalized procedure for HAp/MOF composites.

Fig. 14. General process of HAp/MOF composite making.

Qutbi et al. synthesized Zn₂(BDC)₂(DABCO) MOF via a solvothermal method by dissolving Zn(OAc)₂·2H₂O, BDC, and DABCO in DMF under reflux conditions, which yielded white crystalline products. The obtained crystals were washed with DMF and vacuum-dried. Subsequently, an HAp/MOF nanocomposite was prepared using an in situ approach. Zinc acetate and HAp were dispersed in DMF, followed by the addition of BDC and DABCO solutions. The mixture was stirred at 90 °C for 15 min, centrifuged, washed, dried at 90 °C, and finally heated at 120–150 °C to obtain the nanocomposite.¹³

Morales-Cámara et al. prepared ZIF-8 by mixing aqueous solutions of Zn(NO₃)₂·6H₂O and 2-methylimidazole, followed by stirring at room temperature for 24 h. The resulting suspension was filtered, washed, and dried. HAp NPs were synthesized by mixing calcium, phosphate, and carbonate sources at 60 °C for 24 h. For the preparation of the ZIF-8@HAp composite, the HAp suspension was first sonicated, after which solutions of Zn(NO₃)₂·6H₂O and 2-methylimidazole were added sequentially. The mixture was stirred for 24 h, filtered, washed, and dried to obtain the ZIF-8@HAp composite.¹⁴

6.1. Fortification of HAp/MOF composites

Fortification refers to the addition of a material or element to enhance the structural, physical, or chemical properties of a substance. In the context of HAp/MOF composites, fortification involves strengthening or improving structural, functional, or physicochemical characteristics by incorporating additional components such as metal species, carbon-based nanomaterials, or polymers. These components interact physically or chemically with the HAp/MOF matrix, leading to improved properties such as mechanical stability, adsorption performance, catalytic activity, biocompatibility, or antimicrobial behavior. While the primary framework of HAp and MOF is generally preserved, fortification mainly aims to create a multifunctional composite with synergistic performance superior to that of the individual components. Table 5 lists the HAp/MOF composites along with other materials that have been added for fortification and their roles.

Table 5. Materials added for fortifying HAp/MOF composites and their role.

HAp/MOF composites	Materials added for fortification	Role of added material for fortification	Reference
Ag NPs decorated HAp/MIL-101(Fe)	Ag and Fe3O4	- Ag: enhanced catalytic efficiency, antibacterial activity	176
		- Fe3O4: enabled magnetic separability
HAP/ZIF-8@PS	PS (polystyrene)	PS increased the specific surface area, pore volume, and pore size of ZIF-8, which enhances adsorption efficiency and antibacterial activity	177
Sr substituted HA-MOF74	Sr	Sr enhanced osteogenesis, bone-implant integration, and improved bioactivity of HAp	178
Zn-MOF coating on MgO/HA	MgO	MgO improves corrosion resistance, mechanical strength, and surface hardness, and also supports HAp and MOF deposition	179
β-Cyclodextrine modified Fe-MOF encapsulated hydroxyapatite	β-Cyclodextrine	β-Cyclodextrine acted as surface modifier of Fe-MIL-88B, increased efficient drug loading and facilitated controlled release	180
HA/GL/Li-MOF	Glycyrrhizin	Glycyrrhizin served as a green capping and surface-modifying agent, stabilized HAp/MOF nanocomposite, and enhanced enzyme immobilization, activity, and stability	181
n-HA@SiO2-ASP-Pd-TAZ-IMI	SiO2 and ASP (asparagine)	- SiO2: strengthened and stabilized the HAp surface, acting as a protective layer, enhances surface area and dispersion	182
		- Asparagine (ASP): functionalized the surface, facilitated Pd immobilization, and enhanced catalytic activity
Fe3O4-HAp@Mg-GA	Fe3O4	Fe3O4 imparted magnetic properties, enhanced antibacterial activity, and maintained good biocompatibility	183
Mannose-functionalized HAp/MIL-88(Fe)	Mannose	Mannose served as a targeting receptor for cancer cells, and enabled selective delivery	184
Cu-MOF@HAp/bacterial cellulose	Bacterial cellulose	Bacterial cellulose: acted as a flexible, hydrophilic, and mechanically strong matrix; enhanced electrolyte wettability, and maintained structural stability	185
Carbon dots-decorated HAp nanowires lanthanide (Tb)-MOF	CDs (carbon dots)	CDs provided blue fluorescence, enhanced electron–transfer interaction with dopamine, and create a ratiometric system with Tb3+’s green light	186
HAp-La-BTC MOFs@Alg-CS	Alg-CS (alginate-chitosan)	- Alg-CS: encapsulated HAp-La-BTC MOFs to form stable bio-hybrid beads, and increased adsorption capacity, reusability, and selectivity	187
SiO2@Fe3O4-HA-MIL-100-GQDs	SiO2, Fe3O4, and GQDs (graphene quantum dots)	- SiO2: stabilized the magnetic core against aggregation, improved biocompatibility, and provided a stable surface for MOF	188
		- Fe3O4: added magnetic properties to enhance targeted drug delivery and easy separation
		- GQDs: enabled in-body imaging, enhanced antioxidant activity, and supported controlled release
Dopamine-assisted Sr-MOF@HAp	PDA (polydopamine)	PDA acted as an adhesive and surface modifier, provided hydrophilic groups, enhanced bonding, growth, and separation efficiency	189
Ag decorated HAp-UiO-66-NH2	Ag	Ag acted as the active catalytic center for the Suzuki–Miyaura cross-coupling reaction	175

6.2. Application of HAp/MOF composites

HAp/MOF composites represent an innovative class of materials where the integration of HAp with MOFs leads to hybrid materials that synergistically combine the biocompatible, osteoconductive, and bone-mimicking properties of HAp. Due to the synergistic effect of their intrinsic and complementary properties, these composites have attracted significant interest for applications in biomedical fields,^180,190,191 environmental remediation,^173,189,192 catalysis,^174,176,193 coating applications,^194,195 electrochemistry,^185,186 and agrochemical applications,¹⁴ among others (Fig. 15a).

Fig. 15. (a) Application of HAp/MOF composites in various fields, and (b) biomedical application of HAp/MOF composites.

6.2.1. Biomedical application

HAp/MOF composites have gained attention in biomedical research because they merge HAp's biocompatibility and bone-like mineral properties with MOFs. These hybrids help overcome some of the individual limitations of HAp and MOFs. For example, it enables multifunctional applications such as drug delivery and controlled release, bone tissue engineering, and antibacterial and anti-infective activities (Fig. 15b).

6.2.1.1. Drug delivery and controlled-release

In HAp/MOF composites, MOFs function as high-capacity drug reservoirs with stimuli-responsive release behavior (e.g., pH or redox sensitivity), while HAp provides biocompatible anchoring and enhanced stability under physiological conditions. For example, Golmohamadpour et al.¹⁸⁰ developed an efficient and robust MOF-based drug delivery system by encapsulating alendronate-loaded Fe-MIL-88B within HAp (Alen@β-CD@Fe-MIL-88B@HAp) that demonstrated satisfactory drug loading and sustained release over 28 days.

Poursadegh et al.¹⁸⁴ synthesized HAp/MIL-88(Fe) nanocomposites via an in situ method and subsequently functionalized them with mannose. The mannose-modified HAp/MIL-88(Fe) was loaded with 5-fluorouracil (5-FU), and in vitro studies showed pH-controlled drug release and significant cytotoxicity against HT-29 colon cancer cells. Karimi et al.¹⁸⁸ reported a novel drug delivery system based on the in situ self-assembly of MIL-100 around pre-synthesized magnetic HAp, followed by capping with fluorescent graphene dots for doxorubicin (DOX) loading and delivery (Fig. 16a). The resulting composite exhibited pH-responsive controlled release of DOX and effective cytotoxicity against MCF-7 breast cancer cells.

Fig. 16. (a) Schematic diagram depicting the fabrication of SiO₂@Fe₃O₄-HA-MIL-100 and its GQD-functionalized counterpart, followed by the loading and subsequent release of the doxorubicin (DOX) chemotherapeutic agent. Reproduced with permission.¹⁸⁸ Copyright 2023, Elsevier B.V., (b) layer-by-layer preparation of bio- and hemocompatible Cu-HKUST-1@HAp composite with antibacterial properties. Reproduced under the terms of the CC BY 4.0 license.¹⁹¹ Copyright 2023, the authors, published by American Chemical Society, (c) visual assessment of antibacterial activity: colony formation on coating surfaces (top) and surrounding inhibition zones (bottom) for the HAp, HAp-Zn, HAp/ZIF-8, and HAp/ZIF-8@Gent coatings. Reproduced under the terms of the CC BY 4.0 license.¹⁹⁶ Copyright 2024 by the authors. Licensee MDPI.

Similarly, Yang et al.¹⁹⁷ loaded DOX into a Fe₃O₄@Fe-MOF@HAp nanocomposite, achieving a high drug loading capacity of up to 75.38 mg g⁻¹. The composite showed pH-sensitive gatekeeping behavior provided by HAp, controlled drug release and efficient tumor cell inhibition.

6.2.1.2. Bone tissue engineering

HAp/MOF composites have emerged as advanced biomaterials for bone tissue engineering by integrating the bone-mimicking and osteoconductive properties of HAp. This synergistic combination helps overcome the inherent brittleness and limited drug-loading capacity of HAp. On the other hand, MOFs contribute to additional functionality that results in scaffolds with enhanced mechanical strength, biocompatibility, and biological performance.

For instance, Fandzloch et al.¹⁹¹ synthesized a Cu-HKUST-1@HA composite via a layer-by-layer approach (Fig. 16b), in which the Cu-HKUST-1 layer improved mechanical properties and imparted strong antibacterial activity. The composite maintained a negative zeta potential, exhibited good biocompatibility toward human dermal fibroblasts, and showed potential for bone tissue regeneration.

Similarly, Sarkar et al.¹⁹⁸ developed a three-dimensional carboxymethyl cellulose-HAp scaffold enriched with dexamethasone-loaded ZIF-8 (HA/DMOF) for localized bone therapy. DMOFs with rhombohedral morphology (60–80 nm) and around 16 wt% drug loading was synthesized via a one-pot method and then incorporated into the cellulose/HAp matrix through an in situ process. The resulting composite exhibited compressive strength of 16.3 ± 1.57 MPa and modulus of 0.54 ± 0.073 GPa which are comparable to human cancellous bone. Controlled dexamethasone release over four weeks was achieved due to matrix protection and strong MOF-polymer interactions. In vitro studies using MC3T3 pre-osteoblasts demonstrated excellent cytocompatibility, enhanced ALP activity, and increased extracellular matrix mineralization compared to HAp alone.

6.2.1.3. Antibacterial and anti-infective applications

HAp/MOF composites exhibit strong antibacterial and anti-infective activity which arise from the controlled release of metal ions or antimicrobial agents from the MOF component. This is also combined with the osteoconductive and biocompatible nature of HAp. Such synergistic interaction disrupts bacterial membranes and inhibits the growth of common pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, while maintaining compatibility with mammalian cells.

Zhang et al.¹⁷⁸ developed Mg-MOF-74/Sr-substituted HAp composite coatings on titanium substrates for treating bone-related injuries complicated by infection or osteosarcoma. In vitro studies demonstrated effective early-stage elimination of S. aureus, E. coli, and Saos-2 cells, followed by enhanced osteoblast proliferation and osteogenic differentiation at later stages. Jia et al.¹⁹⁶ fabricated a gentamicin-loaded ZIF-8 nanolayer grown on plasma-sprayed HAp coatings. The resulting HAp/ZIF-8@Gent system exhibited sustained drug release and significantly enhanced antibacterial activity against E. coli (Fig. 16c).

Mousavi et al.¹⁸³ reported a multifunctional Fe₃O₄-HAp@MG-GA bionanocomposite with controlled gallic acid release, strong antibacterial efficacy against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, and good cytocompatibility. The synthesized material highlighted its potential for infection control and wound-related therapies. In another study, Bodylska et al.¹⁹⁰ combined HAp NPs with MIL-125(Ti)–NH₂ and further loaded gentamicin. The composite achieved significant improvement of antibacterial performance against S. aureus and P. aeruginosa.

6.2.2. Environmental remediation

HAp/MOF composites have gained increasing attention for environmental remediation, particularly in water purification applications involving the removal of heavy metals, dyes, antibiotics, and oil contaminants, as well as photocatalytic degradation of emerging pollutants.

6.2.2.1. Heavy metal removal

HAp/MOF composites are highly effective for the removal of toxic heavy metal ions such as Ni²⁺, Pb²⁺, Cd²⁺, and U(vi). The removal mechanisms generally involve electrostatic attraction, ion exchange, and surface complexation within the porous MOF framework which is complemented by the ion-exchange capacity of HAp. Xuan et al.¹⁵ synthesized a nanoscale HAp-modified ZIF-67 composite (HAp/ZIF-67) via an ultrasound-assisted route for efficient U(vi) removal (Fig. 17a). The composite exhibited strong selectivity and achieved 97.29% uranium removal from real wastewater. Similarly, Foroutan et al.¹⁹² developed a biocompatible HAp derived from chicken beak, subsequently modified with ZIF-8 (HApB/ZIF-8), which showed high adsorption capacity, excellent reusability, and effective Ni²⁺ removal from aqueous media.

Fig. 17. (a) Selective elimination of uranium(vi) from wastewater by HAp modified ZIF-67 composite. Reproduced with permission.¹⁵ Copyright 2021, Elsevier B.V., (b) probable adsorption mechanism of tetracycline (TC) and ciprofloxacin (CIP) on HAP/MIL-101(Fe)/Fe₃O₄ nanocomposite. Scheme adapted from ref. 173 published by Royal Society of Chemistry (2022), is licensed under CC BY-NC 3.0. (c) Fabrication process of dopamine-assisted Sr-MOF@HAp for ultrafast oil–water and crude oil separation. Reproduced with permission.¹⁸⁹ Copyright 2025, Elsevier B.V., and (d) defluoridation of water by HAp-La-BTC-MOFs. Reproduced with permission.¹⁹⁹ Copyright 2022, Elsevier B.V.

6.2.2.2. Removal of organic pollutants (dyes, antibiotics, and oils)

HAp/MOF composites have been widely explored for the removal of organic pollutants, including dyes and antibiotics (e.g., Congo red, Rose Bengal, tetracycline, and ciprofloxacin). The high surface area and pore volume of MOFs facilitate pollutant adsorption, while HAp contributes additional ion-exchange sites and surface interactions. In some systems, MOFs also impart catalytic functionality for pollutant degradation rather than simple adsorption.

Beiranvand et al.¹⁷³ fabricated a magnetic HAP/MIL-101(Fe)/Fe₃O₄ nanocomposite that exhibited high adsorption capacities for tetracycline (95%) and ciprofloxacin (93%), along with good reusability and magnetic recoverability (Fig. 17b). Kanmaz and Demircivi²⁰⁰ reported a UiO-66@HAp composite for tetracycline removal with 82.5% efficiency after seven cycles and showed versatility in different water matrices. Qutbi et al. achieved over 98% tetracycline removal using a Zn₂(BDC)₂(DABCO) MOF/HAp nanocomposite.¹³ Additionally, Hou et al.¹⁸⁹ developed a polydopamine-assisted Sr-MOF@HAp membrane for ultrafast oil–water separation with 99.2% separation efficiency for n-hexane emulsions and simultaneous removal of metal salts and ions (Fig. 17c). Mishra et al.²⁰¹ synthesized a cost-effective HAp@ZIF-8 composite from rohu fish scales for Rose Bengal dye removal. They demonstrated good stability, reusability, and compatibility with various water matrices.

6.2.2.3. Defluoridation

HAp/MOF composites are highly effective adsorbents for removing excess fluoride from contaminated water. Jeyaseelan et al.¹⁹⁹ developed a HAp-layered lanthanum-BTC MOF (HAp-La-BTC) via a template-directed layer-by-layer approach. In this work, hydrothermally synthesized HAp nanorods guided the nucleation and growth of La-BTC through electrostatic interactions and coordination with La³⁺ ions (Fig. 17d). Comprehensive characterization confirmed successful composite formation. The material exhibited a maximum fluoride adsorption capacity of 4.267 mg g⁻¹ at 323 K which is approximately 3.3 times higher than pristine HAp. Adsorption followed the Langmuir isotherm and pseudo-second-order kinetics, indicating chemisorption. Thermodynamic analysis revealed a spontaneous and endothermic process. The composite also demonstrated high regenerability (>85% capacity retention) and effective performance in real groundwater.

In related studies, Jeyaseelan et al.¹⁸⁷ reported HAp-implanted La-BTC MOF biopolymeric beads (HAp-La-BTC@Alg-CS) with a fluoride adsorption capacity of 4668 mg F⁻ kg⁻¹, while Jeyaseelan and Viswanathan²⁰² achieved a higher capacity (4865 mg F⁻ kg⁻¹) using cerium-based analogues (HAp-Ce-BTC@Alg-CS). Additionally, Kumari et al.²⁰³ synthesized an aluminum fumarate-HAp composite (AlFu-HAp) via solid–solid mixing. The composite achieved over 90% fluoride removal efficiency and highlighted its potential for practical water treatment applications.

6.2.3. Catalytic application

HAp/MOF composites also emerged as efficient heterogeneous catalysts for a wide range of reactions: photocatalysis, nitroaromatic reduction, esterification, transesterification, and advanced oxidation processes. The enhanced catalytic performance arises from the synergistic integration of MOFs' high surface area and tunable active sites with the structural stability, adsorption capacity, and biocompatibility of HAp.

6.2.3.1. Reduction of nitroaromatic compounds

Beiranvand et al. synthesized a multifunctional Ag/Fe₃O₄-decorated HAp/MIL-101(Fe) nanocomposite (HAp/MIL-101(Fe)/Ag/Fe₃O₄) as a magnetically recoverable heterogeneous catalyst for the NaBH₄-mediated reduction of toxic nitroaromatic pollutants.¹⁷⁶ The composite was fabricated via a stepwise strategy involving hydrothermal synthesis of HAp nanorods, co-precipitation of Fe₃O₄, chemical reduction of Ag NPs, and solvothermal formation of MIL-101(Fe). The catalyst demonstrated rapid reduction of multiple nitroaromatics: 4-NP, 2-NP, 2,4-NP, 4-NA, and 2-NA, which were converted to their amine derivatives within 8–18 min (Fig. 18a). The rate constant values were 0.2, 0.3, 0.33, and 0.47 min⁻¹, respectively. The enhanced activity was attributed to Ag NPs serving as active sites, MIL-101(Fe) providing high surface area, HAp offering adsorption and stability, and Fe₃O₄ enabling magnetic recovery.

Fig. 18. (a) Time-dependent UV-vis absorption profiles for the NaBH₄-mediated reduction of four nitroarenes (2-NP, 2,4-NP, 4-NA, 2-NA) catalyzed by HAp/MIL-101(Fe)/Ag/Fe₃O₄. Standard conditions: [nitroarene] = 0.2 mM, [NaBH₄] = 20 mM, catalyst loading = 5 mg, T = 25 °C. Adapted from ref. 176 published by Royal Society of Chemistry (2023), is licensed under CC BY-NC 3.0. (b) Schematic diagram depicting the proposed mechanism for synergistic radical generation and organic compound degradation in the HAnW@CoMOF-activated peroxymonosulfate (PMS) system. Reproduced with permission.²⁰⁴ Copyright 2021, American Chemical Society, and (c) Pd-free HAp@UiO-66-NH₂/Ag catalyst for Suzuki–Miyaura cross-coupling reactions. Reproduced with permission.¹⁷⁵ Copyright 2025, Elsevier B.V.

6.2.3.2. Photocatalysis and advanced oxidation

Bharali et al.¹⁹³ developed a Co–Cu/ZIF@HAp composite via in situ growth of bimetallic ZIF on HAp. The composite showed efficient photocatalytic degradation of Eosin Yellow and Brilliant Green with excellent durability over five reuse cycles. Similarly, Li et al.²⁰⁴ synthesized a HAp-based heterojunction catalyst (HAnW@Co-MOF) which is capable of activating peroxymonosulfate for advanced oxidation of various organic pollutants. These pollutants included tetracycline and multiple dyes, and demonstrated high degradation efficiency and stability (Fig. 18b). D. C. Español et al.²⁰⁵ reported an ultrasound-assisted HAp/MOF photocatalyst for effective degradation of metformin under different operational conditions.

6.2.3.3. Esterification, transesterification, and cross-coupling reactions

Bharali et al.¹⁷⁴ synthesized a ZIF-4@HAp nanocomposite that acted as an efficient heterogeneous catalyst for solvent-free base-catalyzed esterification and achieved ≥90% yields within 2 h. Kalita et al.²⁰⁶ reported a UiO-66@HAp catalyst with excellent reusability for biodiesel production via transesterification of palm oil. Kefayati et al.¹⁸² developed an HA-supported Pd-based MOF catalyst for nitroarene reduction and dye degradation with high catalytic efficiency and recyclability. Furthermore, Soltanmoradi et al.¹⁷⁵ introduced a Pd-free HAp@UiO-66-NH₂/Ag catalyst for Suzuki–Miyaura cross-coupling reactions, exhibiting excellent activity toward various aryl halides, including chlorobenzene, and maintaining performance over at least eight cycles (Fig. 18c).

6.2.4. Coating applications

HAp/MOF composites have emerged as advanced fillers for epoxy-based anticorrosion coatings, particularly for metals exposed to saline and marine environments. These composites enhance coating performance by blocking corrosive species, pH-responsive self-healing, and ensured long-term protection without relying on toxic inhibitors. In such systems, HAp improves pore filling and interfacial adhesion, whereas MOFs provide high inhibitor loading capacity and stimulus-triggered release. It enabled combined passive and active corrosion protection.

Guo et al.¹⁹⁴ developed a pH-responsive HAp/MOF nanocontainer system for long-term anticorrosion protection in epoxy coatings (Fig. 19a). HAp nanosheets were first synthesized hydrothermally, followed by in situ growth of ZIF-8 on the HAp surface to form core–shell HAp@ZIF-8 (H-Z). Benzotriazole (BTA) was subsequently loaded into ZIF-8 pores via vacuum-assisted impregnation, and resulted in HAp@ZIF-8/BTA (HZB) nanocontainers. The HZB nanocontainers were uniformly dispersed in epoxy resin with a polyamide curing agent and spray-coated onto steel substrates (≈80–100 µm thickness). Compared to pristine HAp, HZB showed improved dispersion, reduced agglomeration, and minimized coating defects. A slight increase in contact angle indicated enhanced hydrophobicity.

Fig. 19. (a) Preparation and anti-corrosion mechanism of HAp@ZIF-8/BTA nanocontainers. Reproduced with permission.¹⁹⁴ Copyright 2023, Elsevier B.V. (b) Schematic illustration of dopamine (DA) sensing by HAPNWsCDs-Tb/MOF which acts as a fluorescent probe. Reproduced with permission.¹⁸⁶ Copyright 2022, Royal Society of Chemistry. (c) Core–shell ZIF-8@HAp composite as a multifunctional agrochemical carrier. Reproduced under the terms of the CC BY 4.0 license.¹³¹ Copyright 2024, the author(s), published by American Chemical Society.

Solaimany et al.²⁰⁷ reported a MoS₂/HAp/ZIF-8 nanocomposite loaded with BTA as a self-healing corrosion inhibitor. The resulting epoxy coating exhibited excellent corrosion resistance in 3.5% NaCl, high impedance retention, strong self-healing behavior, improved adhesion, reduced cathodic disbandment, and enhanced durability. In another study, Solaimany et al.¹⁷² designed a triple-ligand MOF system (mix@HA/Z8) loaded with BTA and zinc nitrate, which was immobilized on HAp sheets to improve barrier and self-healing properties. The mix@HA/Z8 coating showed the highest corrosion inhibition efficiency, low adhesion loss (21.21%), and stable impedance after 56 days in saline solution.

He et al.¹⁹⁵ developed tannic acid-decorated HAp/ZIF-8 composite fillers dual-loaded with 2-aminobenzothiazole (2-ABT). The resulting coating exhibited improved corrosion resistance, enhanced mechanical strength on Q215 steel, and maintained high impedance after 28 days of immersion. Similarly, Liu et al.²⁰⁸ introduced HAp/ZIF nanocontainers into epoxy matrices to achieve strong barrier protection, real-time corrosion self-diagnosis, and stimulus-responsive self-healing, resulting in long-term durability and reliable corrosion protection.

6.2.5. Electrochemical applications

HAp/MOF composites are used in electrochemical applications such as sensing and energy storage systems. This becomes possible due to the synergistic integration of HAp's chemical stability, and ion-exchange capability, tunable porosity, and active metal sites of MOFs. Sun et al.¹⁸⁶ developed a ratiometric fluorescent probe based on HAp nanowires (HAPNWs) which is co-decorated with carbon dots (CDs) and a terbium-based MOF (Tb-MOF). The composite (HAPNWs-CDsTb/MOF) enabled sensitive and selective detection of dopamine. Dopamine is a neurotransmitter that is related to neurological disorders like Parkinson's and Alzheimer's disease. Herein, HAPNWs were synthesized by solvothermal techniques. CDs were prepared hydrothermally and attached electrostatically. Tb-MOF was grown in situ to form a spinning-like MOF structure on the nanowires (Fig. 19b). In HEPES buffer (pH 8.0), dopamine enhanced Tb³⁺ emission by coordinating with the metal centers and simultaneously quenched CD emission through photoinduced electron transfer. This dual-response mechanism produced a visible fluorescence color shift and a linear ratiometric response (I₅₄₃/I₄₂₆) over a dopamine concentration range of 0.04–20 µM (R² = 0.998), with a detection limit of 12.26 nM. The probe showed excellent selectivity and achieved recoveries of 100.8–103.3% in diluted human serum.

In energy storage applications, Cheng et al.¹⁸⁵ developed a Cu-MOF-functionalized HAp/bacterial cellulose (Cu-MOF@HB) separator for lithium-ion batteries. The porous structure and exposed metal sites facilitated fast Li⁺ transport, reduced polarization, suppressed dendrite growth, and improved coulombic efficiency. The separator achieved 79% capacity retention after 600 cycles. Additionally, enhanced thermal stability and flame retardancy that indicated improved safety and fast-charging performance.

6.2.6. Agrochemical applications

HAp/MOF composites are emerging as smart delivery platforms for fertilizers and pesticides. They also enable controlled and sustained release of active components and minimizes environmental contamination. The synergy between HAp's biocompatibility, nutrient affinity, and structural stability and MOF's high loading capacity and tunable release behavior makes these composites attractive for sustainable agriculture.

Morales-Cámara et al.¹⁴ synthesized a core–shell ZIF-8@HAp composite as a multifunctional agrochemical carrier (Fig. 19c). ZIF-8 was prepared by mixing zinc nitrate and 2-methylimidazole in water. HAp nanoparticles were synthesized separately from calcium and phosphate precursors. The composite was formed via in situ growth of ZIF-8 on HAp particles. The ratio of ZIF-8/HAp was kept at 1000 : 1 that resulted in a uniform shell. Compared to bare ZIF-8, the ZIF-8@HAp composite exhibited significantly enhanced stability in aqueous and acidic environments. While pure ZIF-8 degraded within 4 h in water, ZIF-8@HAp remained stable for up to 7 days. In acidic media (pH 4.5), Zn²⁺ release from ZIF-8@HAp was slower and more controlled than from pure ZIF-8. Fertilizer performance tests on wheat seeds showed notable improvements in plant growth. Root and shoot lengths increasing by 27.1% and 9.4%, respectively, compared to water controls. HAp alone showed moderate effects, whereas ZIF-8 alone exhibited negligible growth enhancement.

7. Composites of hydroxyapatite/MXene (HAp/MXene)

Hydroxyapatite is an inorganic ceramic material having structural similarity to human bone tissue and MXene is transition metal carbides or nitrides obtained from MAX phases.^209,210 HAp/MXene composite combines the biocompatibility, osteoconductivity, and bioactivity of HAp with exceptional electrical conductivity, mechanical strength and photothermal properties of MXenes.²¹¹ These composites have gained significant interest for applications in biomedical fields, for example, tissue engineering, drug delivery and antimicrobial coatings, and environmental remediation like oil–water separation, dye-salt separation etc.^210,212

7.1. Synthesis procedures of HAp/MXene composite

The HAp/MXene composites are typically synthesized via two methods: in situ and ex situ synthesis.

7.1.1. In situ synthesis of HAp/MXene composite

One of the most common approaches of HAp/MXene composite is the in situ growth of HAp on multilayered MXene via hydrothermal treatment. In this process, calcium and phosphate precursors are introduced to a colloidal suspension of MXene under controlled temperature and pressure.²⁰⁹ This results in uniform distribution of HAp particles on the MXene surface and interlayers and improves stability and bioactivity.²¹² For example, Jiang et al. synthesized HAp/MXene composites where NH₄H₂PO₄ and Ca(NO₃)₂·4H₂O were weighed and dissolved in water to achieve a 1.67 molar ratio of Ca/P. By adding ammonia, pH was adjusted to 9–10. The solution was transferred to a hydrothermal reactor with various amounts of MXene and the reaction was carried out for 3 hours at 120 °C. After cooling, the products were washed three times with ethanol and DI water, then dried at 60 °C in an oven to obtain HAp/MXene powder.²¹² The schematic representation of the in situ synthesis is demonstrated in Fig. 20a.

Fig. 20. (a) Schematic representation of the synthesis of HAp/MXene composite which involves etching the MAX phase, followed by addition of Ca and P precursors for in situ HAp formation around MXene, and (b) schematic representation of ex situ synthesis of HAp/MXene composite.

7.1.2. Ex situ synthesis of HAp/MXene composite

A simple and widely used technique for the fabrication of HAp/MXene composite is ex situ physical blending.²¹³ In this process, pre-synthesized MXene nanosheets and HAp are typically dispersed in deionized water using ultrasonication to acquire uniform suspensions. After that, the HAp dispersion is mixed with MXene colloidal solution to promote mixing. At room temperature, the mixture is stirred overnight and freeze-dried to obtain the nanocomposite powder. For instance, Zhang et al. dispersed freeze-dried MXene prepared by minimal intensive layer delamination method and HAp powders each in deionized water at 5 mg mL⁻¹ concentration using ultrasonication. Then, the n-HAp dispersion was added gradually to the colloidal solution of MXene while stirring. After overnight stirring, at 25 °C and by freeze drying the final product was formed. By this process, nanocomposites with 90%, 70% and 50% MXene content were prepared owing to the varied mass ratios of MXene to n-HA (9 : 1, 7 : 3, 1 : 1) used.²¹¹ The schematic representation of the ex situ formation of HAp/MXene composite is given in Fig. 20b.

7.2. Fortification of HAp/MXene composite

Fortification of HAp/MXene composites is typically carried out by adding materials like gold nanorods (AuNR), polydopamine (PDA), Ti, Ag, polyvinyl alcohol (PVA), quantum dots (QDs) etc. This fortification improves certain qualities of the HAp/MXene composite that widens the applicability of the composite. The added materials improve properties such as tensile strength, compressive strength, and photothermal effects, antibacterial activity, biocompatibility and osteogenic potential. The use of various fortification materials and their effects are presented in Table 6.

Table 6. Materials added for fortifying HAp/MXene composites and their role.

HAp/MXene composites	Materials added for fortification	Role of added material for fortification	Ref.
Ti3C2@AuNRs/HAP/PDA	AuNRs, polydopamine (PDA)	- AuNR: photothermal enhancement	214
		- PDA: increased drug adhesion, drug loading capacity, improves biocompatibility
Chitosan/HApTi-MXene	Chitosan	Provided biocompatibility, biodegradability, and antibacterial activity. Also acted as the primary polymer matrix and hydrogel former in the scaffold	215
PVA/n-HA/MXene	Polyvinyl alcohol (PVA)	Provided film-forming ability and structural integrity. Improved mechanical strength and flexibility. Controlled swelling and degradation behavior	216
MXene-quantum dots-hydroxyapatite (MQDS-HA)	Quantum dots (QDs)	- MQDS: large BET surface area, good fluorescence, low toxicity, mild and controlled drug storage-release behavior	16
MXene/HAp/halloysite/PLA coatings on Mg	Halloysite and polylactic acid (PLA)	- Halloysite: nanotubular ceramic filler in the PLA-HA coating; enhanced bioactivity and apatite formation in SBF	17
		- PLA: formed protective barrier on Mg to slow corrosion; ensured good adhesion of HA, HNT and MXene to Mg
MXene/Ag-HA	Ag	Antibacterial ion fortification, osteoconductive support, brittleness compensation	217

7.3. Applications of HAp/MXene composite

HAp/MXene is a promising composite material for biomedical uses such as tissue engineering, bone regeneration, bone repair, and environmental remediation like dye or salt separation, and oil or water separation. In this composite, HAp provides excellent bioactivity, cell proliferation, osteogenic differentiation and supports bone cell growth. On the other hand, MXene gives better mechanical strength, electrical properties, and photothermal effects under near-infrared (NIR) to improve the healing process. Additionally, the hydrophilic nature of HAp along with MXene's layered structure and unique surface properties make the composite able to separation oil/water at high flux and rejection rate. They are also able to remove dyes from wastewater through filtration and adsorption.^{212,215,217,218}

7.3.1. Biomedical application

MXenes are well-known for their high conductivity, photothermal efficiency, hydrophilicity and antibacterial properties, and HAp is a key component of bone.¹⁸ As a result, HAp/MXene when combined, shows enhanced mechanical, phototherapeutic, osteogenic and antimicrobial performance.^18,211 In addition, HAp/MXene composite membrane and scaffolds are now widely used for bone-related therapies such as drug delivery, guided bone regeneration, bone defect repair, antibacterial and implant coating, and tumor treatment.^217,219

7.3.1.1. Bone tissue engineering

The recent advancements in the bone tissue engineering field have explored that HAp/MXene nanocomposites can be used to address issues like bone defects, infections, and insufficient osteogenesis. One of the most common approaches of treating bone defects is guided bone regeneration (GBR) using biological barrier membranes. They promote the growth of epithelial cells, fibroblasts and ensure the growth of more slowly proliferating osteoblasts and blood vessels. Polyvinyl alcohol is widely used for preparing GBR membranes owing to their good hydrophilicity, biocompatibility, and film-forming properties; however, it is not biodegradable. This is why it is combined with other materials to increase its degradation rate such as HAp. In addition, MXene can also be used in GBR as it is biodegradable and has good biocompatibility and antimicrobial properties. Yang et al.²¹⁶ synthesized n-HAp/PVA/MXene composite by mixing them in water and the solution was freeze-dried to obtained the crosslinked membranes. These membranes showed enhanced mechanical strength which indicates their ability to prevent any tear in the membrane (Fig. 21). Additionally, the membrane showed a reduced swelling rate indicating its stability and improved degradation rate. Due to the addition of MXene, the PVA/n-HAp/MXene composite membrane showed antibacterial properties, which are essential to prevent infection.²¹⁶

Fig. 21. Preparation of the PVA/n-HAp/MXene composite by dispersing MXene, n-HAp, PVA in water and then keeping it in a mold, followed by freeze-drying. The membranes were then cut into pellet to use for guided bone regeneration. Reproduced with permission, Copyright 2024, Elsevier Ltd.²¹⁶.

Furthermore, Veerabathiran et al. used 3D bioprinting to prepare chitosan/HAp hydrogels incorporated with Ti-MXene.²¹⁵ In this case, HAp was formed by mixing calcium nitrate and diammonium hydrogen phosphate. Afterwards, extrusion of bioink was carried out to yield scaffolds with tensile strength up to 23.3 MPa, low swelling, and degradation, superior antibiofilm properties, and high cell viability toxicity.²¹⁵ Another approach for synthesizing HAp/MXene composite was employed where ultralong HAp nanowires were dispersed in MXene and water to produce free-standing membranes. These membranes showed tunable mechanical properties, MC3T3-E1 adhesion, proliferation, osteogenic gene expression and in vivo bone regeneration in rat calvarial defects.²²⁰ Besides, Li et al.²¹⁷ synthesized an injectable MXene/Ag-HAp hydrogel to address the challenges associated with bone substitutes. This composite showed excellent biocompatibility, antibacterial properties and mechanical strength. Cui et al.²²¹ prepared HAp-MXene nanocomposite by incorporating HAp around MXene nanosheets which boosted macrophage M1 and M2 polarization as well as showed pH sensititve Ca²⁺ release. By this dual macrophase acceleration, the process of bone defect repair could be optimized.²²¹

7.3.1.2. Drug delivery applications

The HAp/MXene composite systems combine the bone-mimicking structure, biocompatibility, and osteoconductivity of HAp with the high drug-binding capacity and photothermal conversion efficiency of MXenes. As a result, HAp/MXene composites enable pH and near-infrared (NIR)-responsive drug release, improved tumor selectivity, and reduced systemic side effects.

Song et al.²¹⁴ reported a core–shell nanoplatform prepared by self-assembly of gold nanorods (AuNRs) onto MXene sheets. Subsequently, in situ self-assembly of HAp was carried out in a calcium–phosphate solution at pH 10, followed by polydopamine (PDA) coating via dopamine polymerization in alkaline buffer (Fig. 22). The resulting composite exhibited excellent photothermal conversion efficiency, high doxorubicin (DOX) loading capacity, and dual-responsive drug release triggered by pH and NIR irradiation.

Fig. 22. Illustration of Ti₃AlC₂@AuNR/HAp/PDA composite's pH and NIR dual drug release mechanism. Reproduced with permission, Copyright 2022, Elsevier Ltd.²¹⁴.

In another approach, in situ hydrothermal growth of n-HAp on multilayer MXene (m-MXene) was achieved by reacting calcium nitrate and diammonium phosphate at pH 10 and 120 °C without additional reagents.²⁰⁹ The resulting m-MXene/n-HAp composite demonstrated high drug-loading efficiency, controlled drug release behavior, strong NIR-induced photothermal performance, good structural stability, and effective cancer cell killing. Furthermore, Liu et al.¹⁶ synthesized MXene quantum dot (MQD)/HAp hollow sphere composites by incorporating MQDs during the formation of HAp hollow structures. This multifunctional system exhibited selective cytotoxicity toward cancer cells, intrinsic fluorescence for bioimaging, and combined chemotherapy and photothermal ablation capability. They also showed potential for bone regeneration.

7.3.1.3. Photothermal therapy for bone tumors

Primary and metastatic bone tumors pose serious clinical challenges. This is because conventional treatments such as surgery, radiotherapy, and chemotherapy often result in incomplete tumor removal and severe bone defects. Photothermal therapy (PTT) has emerged as a promising alternative because cancer cells are more susceptible to hyperthermia than normal cells.²²² MXenes are particularly attractive photothermal agents due to their high NIR absorption and photothermal conversion efficiency.²²³ On the other hand, n-HAp can inhibit cancer cell proliferation, induce apoptosis, and promote bone regeneration owing to its excellent bioactivity and osteogenic properties.²²⁴

Zhang et al.²¹⁹ developed a porous n-HAp/g-C₃N₄/MXene scaffold that enabled synergistic photothermal and photodynamic therapy under NIR irradiation (Fig. 23). In this system, n-HAp was synthesized hydrothermally, while graphitic carbon nitride (g-C₃N₄) was obtained by calcining melamine foam. MXene and n-HAp were subsequently incorporated into a chitosan matrix to form the final scaffold. Under NIR exposure, the composite rapidly heated to ∼59 °C and generated reactive oxygen species, leading to near-complete tumor cell ablation within 10 min. Additionally, the scaffold promoted adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs). In vivo studies showed up to 98% tumor shrinkage in tumor-bearing mice under NIR irradiation, confirming its therapeutic potential.

Fig. 23. Schematic representation of simultaneous photothermal ablation of bone tumors and bone tissue regeneration via n-HA/g-C₃N₄/MXene scaffold. Reproduced with permission, copyright, 2025, Elsevier Ltd.²¹⁹.

In a related study, Zhang et al.²¹¹ prepared an n-HAp/MXene nanocomposite via simple ultrasonication of n-HAp and MXene in deionized water. The composite exhibited excellent photothermal performance under 808 nm NIR irradiation. Additionally, the nanocomposite showed good biocompatibility, enhanced cell adhesion, proliferation, and osteogenic differentiation of BMSCs. This highlights its suitability for bone tumor therapy and regeneration.

7.3.1.4. Antibacterial and coating applications

Magnesium alloys are widely used in biomedical implants because of their biocompatibility, biodegradability, and low Young's modulus. However, their rapid corrosion and hydrogen gas evolution in physiological environments can lead to premature implant failure. Surface coatings are therefore essential to improve corrosion resistance and biological performance.

HAp/MXene composites have been explored as multifunctional coating materials, where HAp provides bioactivity and osteointegration, and Ti₃C₂T_x MXene contributes antibacterial activity through membrane disruption mechanisms. Topuz et al.¹⁷ fabricated a composite coating by spin-coating a PLA-HAp-HNT/MXene suspension onto magnesium substrates. The incorporation of MXene significantly reduced the contact angle, indicating improved surface hydrophilicity and wettability. Electrochemical measurements showed a high polarization resistance (∼2.36 × 10¹⁴ Ω cm²), demonstrating excellent barrier protection and slowed magnesium degradation. After immersion in simulated body fluid (SBF) for 15 days, dense calcium phosphate deposition was observed on the coated surface, confirming enhanced bioactivity. Moreover, the MXene-containing coatings exhibited strong antibacterial performance against Escherichia coli, producing the largest inhibition zones among the tested samples (Fig. 24a).

Fig. 24. (a) Schematic representation of PHH/MXene composite's antibacterial activity by creating inhibition zone. Reproduced under the terms of the CC BY 4.0 license, the authors, published by Journal of Magnesium and Alloys,¹⁷ (b) schematic illustration of an HAp/MXene composite membrane with a 3D mountain-like topography for ultrafast dye/salt separation, demonstrating increased roughness, porosity and surface area. Reproduced with permission, Copyright 2025, Elsevier Ltd.²¹⁸.

7.3.2. Wastewater treatment applications

The rapid growth of textile dyeing, electroplating, and pharmaceutical manufacturing industries has resulted in the discharge of complex wastewater streams. These streams contain oily emulsions, persistent dyes, and high concentrations of inorganic salts (e.g., NaCl, MgCl₂, Na₂SO₄etc.).^225,226 These pollutants pose serious risks to aquatic ecosystems and public health. To address this challenge, membrane separation has emerged as an efficient and scalable wastewater treatment strategy. MXenes are attractive membrane materials due to their tunable interlayer spacing, high mechanical strength, and abundant surface functional groups (–OH, –F, –O).²²⁷ However, MXene nanosheets tend to restack during membrane fabrication, which reduces permeability and separation efficiency. To overcome this limitation, HAp has been introduced as a one-dimensional (1D) spacer.²¹⁸ Owing to its excellent chemical stability, ion-exchange capability, large surface area, and multiple adsorption sites, HAp effectively prevents MXene restacking and enhances oil/water and dye/salt separation performance. The resulting HAp/MXene composite membranes exhibit strong synergistic effects, combining high separation efficiency with long-term structural and operational stability.²¹⁸

7.3.2.1. Dye/salt separation

Conventional polyamide-based nanofiltration membranes often suffer from low water permeability and poor dye/salt selectivity due to the inherent permeability and selectivity trade-off. In contrast, HAp/MXene composite membranes demonstrate superior separation performance in mixed dye/salt systems across a wide range of solute concentrations with excellent long-term usability. This enhanced performance arises from the formation of efficient transport channels, increased membrane porosity, and effective suppression of MXene nanosheet restacking.²¹⁸

Zhao et al. synthesized Ti₃C₂T_x MXene via selective etching and exfoliation of the MAX phase, while HAp nanowires were prepared using a solvothermal method. To fabricate the composite membrane, MXene was first dispersed in deionized water and sonicated for 30 min, followed by the addition of HAp nanowires in varying amounts. The resulting suspension was vacuum-filtered onto a polydopamine (PDA)-coated polyethersulfone (PES) substrate to obtain the HAp/MXene composite membrane.²¹⁸ The fabricated membranes exhibited excellent separation performance and achieved around 98% rejection of Congo red dye by maintaining a low salt rejection (∼15%) for various inorganic salts. It demonstrated the effective dye/salt selectivity of the prepared composite. Notably, the membrane retained high Congo red rejection (∼98%) over a concentration range of 10–50 mg L⁻¹, indicating robust stability. Antifouling tests further confirmed durability, with the membrane maintaining a dye rejection rate of 91.67% after five fouling–cleaning cycles (Fig. 24b).

7.3.2.2. Oil/water separation

Conventional wastewater treatment techniques such as gravity separation and bioremediation are commonly applied for oil/water separation. However, these methods often suffer from low separation efficiency, high energy consumption, and the risk of secondary contamination. These make it difficult to meet stringent environmental standards. In contrast, HAp/MXene composite membranes have emerged as highly efficient materials for oil/water separation.

Jiang et al.²¹² synthesized an HAp/MXene composite by in situ hydrothermal growth of HAp on MXene nanosheets. The composite membrane was fabricated via vacuum-assisted filtration onto a cellulose acetate substrate. The resulting membrane exhibited excellent separation performance for five different oil types and achieved oil/water separation efficiencies of more than 99.2% in all cases (Fig. 25). Notably, the membrane maintained a high separation efficiency of 99.1% even after 10 reuse cycles which demonstrated a substantial durability and reusability. Furthermore, the membrane was evaluated under real environmental conditions. After five operational cycles in actual water and soil environments, the separation efficiency remained as high as 84%, indicating robust performance beyond laboratory conditions. These results highlight the strong potential of HAp/MXene composite membranes for practical and long-term oil/water separation applications in complex environmental systems.

Fig. 25. Schematic representation of the fabrication of HAp/MXene composite membrane following three steps: selective etching of Ti₃AlC₂ using LiF/HCl to obtain MXene, in situ growth of HAp on MXene, and vacuum-assisted filtration to obtain HAp/MXene composite membrane, demonstrating excellent oil/water separation ability. Reproduced with permission, Copyright 2025, Elsevier Ltd.²¹².

Based on all the available knowledge presented in this review on HAp/MOF and HAp/MXene composites, a comparative assessment has been made and presented in Table 7.

Table 7. Comparative overview of HAp/MOF and HAp/MXene composites.

Aspect	HAp/MOF composites	HAp/MXene composites
Role of HAp	Matrix/core providing biocompatible anchoring, ion-exchange capacity, and structural stabilization for the fragile MOF framework	Matrix/core and 1D spacer providing biocompatibility, structural support, and prevention of MXene nanosheet restacking
Typical fabrication routes	(i) In situ growth: MOF directly grown on pre-synthesized HAp surface, ensuring strong interfacial bonding; (ii) post-synthetic impregnation: pre-synthesized MOF physically combined with HAp via solvent-assisted filling	(i) In situ synthesis: HAp precipitated hydrothermally onto MXene suspension (Ca/P precursors added directly to MXene colloid); (ii) ex situ synthesis: separately prepared HAp and MXene dispersions combined by ultrasonication and freeze-drying
Interfacial interaction	Coordination bonding between HAp surface ions (Ca2+, PO43−, OH−) and MOF metal nodes/linkers; electrostatic and ion-exchange interactions	Electrostatic interaction and hydrogen bonding between HAp surface groups and MXene surface terminations (–O, –OH, –F); HAp nanowires/particles physically intercalate between MXene sheets, limiting restacking
Key functional contribution of partner	High surface area, tunable porosity, stimuli-responsive (pH/redox) behavior, diverse chemical functionality	Metallic electrical conductivity, strong NIR photothermal response, mechanical reinforcement, rich surface terminations
Fortification strategies reported	Metal NPs (Ag, Fe3O4), polymers (PS, Alg-CS), biomolecules (β-cyclodextrin, glycyrrhizin, mannose), carbon dots, GQDs	Gold nanorods (AuNRs), polydopamine (PDA), chitosan, PVA, quantum dots, halloysite/PLA, Ag
Major application areas	Biomedical (drug delivery, bone tissue engineering, antibacterial), environmental remediation (heavy metal removal, dye/antibiotic adsorption, defluoridation), catalysis (nitroaromatic reduction, photocatalysis, esterification/cross-coupling), coatings (anticorrosion), electrochemical sensing, agrochemical delivery	Biomedical (bone tissue engineering, drug delivery, photothermal tumor therapy, antibacterial coatings), environmental remediation (oil/water separation, dye/salt separation)
Reported advantages	Very high surface area and porosity enable high drug/pollutant loading capacity; tunable, stimuli-responsive release; broad chemical functionality via linker/metal choice	High electrical conductivity and strong NIR absorption enable combined photothermal/chemotherapy and real-time diagnostic function; good mechanical reinforcement of HAp scaffolds
Reported limitations	MOF component remains moisture- and pH-sensitive even after compositing; many studies report only short-term (days to weeks) stability data; metal-ion leaching from MOF nodes not systematically studied	MXene oxidation in aqueous/ambient conditions is only partially mitigated by HAp; dose-dependent cytotoxicity reported in some biomedical studies; HF-based etching route raises safety/toxicity concerns upstream of composite fabrication

7.4. Critical assessment on synergy, reproducibility and application

The following sections critically assess some of the most important aspects of HAp/MOF and HAp/MXene composites.

7.4.1. Synergistic performance of HAp-based hybrid composites

Only few studies have demonstrated true synergistic effects by directly comparing the performance of the composite with that of its individual components under identical experimental conditions. Among the examples reviewed, Xuan et al.¹⁵ reported that the HAp/ZIF-67 composite exhibited a significantly higher U(vi) adsorption capacity than either pristine HAp or ZIF-67, confirming that the enhanced performance resulted from the combination of both materials rather than from the individual constituents alone. Similarly, the improved water and acid stability of ZIF-8@HAp compared with pristine ZIF-8 indicates a clear synergistic interaction between the two phases.

In contrast, several reported composites achieve improved performance through complementary functions of the individual components rather than through a true synergistic effect. For example, in the Ag/Fe₃O₄/HAp/MIL-101(Fe) catalyst reported by Beiranvand et al.,¹⁷⁶ Ag nanoparticles serve as the catalytic active sites, MIL-101(Fe) provides a high surface area, HAp enhances adsorption and structural stability, and Fe₃O₄ enables magnetic recovery. Likewise, in HAp/MXene photothermal systems, MXene primarily provides photothermal conversion, whereas HAp contributes osteogenic activity. Although these multifunctional composites exhibit superior overall performance, the individual components largely retain independent roles. Future studies should therefore include systematic comparisons with the corresponding single-component materials to distinguish genuine synergistic enhancement from additive or complementary effects.^14,15

7.4.2. Reproducibility of synthesis strategies

The synthesis of HAp/MOF and HAp/MXene composites generally follows either an in situ growth strategy or an ex situ (post-synthetic) assembly approach. In situ synthesis typically produces stronger interfacial interactions and a more uniform distribution of the secondary component because crystal nucleation occurs directly on the HAp surface. Consequently, this strategy has been widely adopted for biomedical and catalytic applications. However, the method requires careful control of synthesis parameters such as pH, precursor concentration, and reaction temperature, while only a few studies have evaluated batch-to-batch reproducibility.

Ex situ assembly offers a simpler and potentially more scalable alternative, as the individual components can be synthesized and optimized separately before composite fabrication. However, physically mixed composites may suffer from weaker interfacial adhesion and particle agglomeration, which can reduce the uniformity of their functional properties.²¹¹ At present, direct comparisons between in situ and ex situ synthesis of identical composite systems are scarce, making it difficult to identify the most reproducible fabrication strategy.

7.4.3. Role of HAp in improving composite stability

The available literature provides convincing evidence that HAp improves the stability of MOF-based composites, whereas similar evidence remains limited for HAp/MXene systems. Morales-Cámara et al.¹⁴ demonstrated that ZIF-8@HAp remained structurally stable in water for up to seven days, whereas pristine ZIF-8 degraded within four hours. The composite also exhibited slower Zn²⁺ release under acidic conditions, suggesting that HAp acts as a protective barrier that reduces water penetration and suppresses framework degradation.

For HAp/MXene composites, the stabilizing effect is mainly structural. HAp particles or nanowires prevent the restacking of MXene nanosheets, thereby preserving interlayer spacing and improving membrane performance.²¹⁸ However, none of the studies reviewed directly investigated whether HAp suppresses the long-term oxidation of MXenes under ambient or aqueous conditions. Since oxidation is one of the major limitations of MXenes, systematic studies addressing this issue are still needed.

7.4.4. Current level of application maturity

The maturity of HAp/MOF and HAp/MXene applications varies considerably and can be assessed from factors such as validation in real samples, long-term cycling performance, and in vivo evaluation. Among HAp/MOF composites, environmental remediation represents the most mature application area. Xuan et al.¹⁵ evaluated uranium adsorption using real wastewater, Kanmaz and Demircivi²⁰⁰ demonstrated stable tetracycline removal over seven adsorption–desorption cycles, and Guo et al.¹⁹⁴ reported long-term anticorrosion performance under saline immersion. In contrast, most biomedical applications remain limited to in vitro investigations, with studies such as Fe₃O₄@Fe-MOF@HAp¹⁹⁷ and mannose-functionalized HAp/MIL-88(Fe)¹⁸⁴ focusing primarily on cultured cancer cell lines without in vivo validation.

HAp/MXene composites have progressed further in biomedical applications. Zhang et al.²¹⁹ demonstrated effective photothermal tumor treatment in mice, while Fu et al.²²⁰ reported successful bone regeneration in a rat calvarial defect model. Environmental applications have also shown encouraging progress, with membrane systems exhibiting stable separation performance under repeated operating conditions.^212,218 Nevertheless, compared with HAp/MOF composites, the application scope of HAp/MXene materials remains relatively limited and has been explored mainly in biomedical and membrane separation fields.

8. Conclusion and future perspectives

HAp-based composites incorporating MOFs and MXenes have emerged as a promising class of multifunctional materials. Throughout this review, we have shown that both composite systems follow a common design strategy where HAp serves as a bioactive and ion-rich scaffold, and MOFs or MXenes provide complementary properties that HAp alone cannot achieve. MOFs contribute high surface area and tunable porosity, whereas MXenes offer excellent electrical conductivity and photothermal performance. This combination has enabled the development of advanced materials for biomedical engineering, environmental remediation, catalysis, electrochemical sensing, protective coatings, and agrochemical delivery.

Despite these advances, the current literature also reveals several important limitations. Most reported studies remain at the laboratory scale, and long-term performance under realistic operating conditions has received limited attention. Stability evaluations are generally restricted to short experimental periods, with few investigations conducted in real wastewater, physiological media, or other application-relevant environments. In HAp/MXene composites, although HAp is frequently proposed to improve MXene stability, direct evidence demonstrating suppression of MXene oxidation is still lacking. Likewise, for HAp/MOF composites, improved structural stability has been reported, but long-term metal-ion leaching from the MOF component has rarely been investigated, despite its importance for biomedical and environmental applications.

Another major challenge is the limited availability of comprehensive toxicity and biocompatibility data. While many studies report promising in vitro results, in vivo validation, long-term biodegradation, and immune response assessments remain scarce, particularly for HAp/MXene composites. Furthermore, many synthesis methods still rely on hazardous chemicals such as HF and high-boiling organic solvents, which limit scalability and practical implementation. The development of greener synthesis strategies, including aqueous synthesis, mechanochemical approaches, and low-toxicity etching methods, together with the use of waste-derived precursors, will be important for future large-scale production.

A further issue identified throughout this review is the lack of standardized reporting. Differences in experimental conditions, performance metrics, and control experiments make direct comparison between studies difficult. Future research should include appropriate component-only controls to distinguish true synergistic effects from simple additive behavior, report long-term cycling and stability data, and evaluate material performance under real operating conditions whenever possible. In addition, a deeper understanding of the HAp-MOF and HAp-MXene interfaces is still needed. Advanced characterization techniques, combined with computational approaches such as density functional theory, molecular dynamics simulations, and machine learning-assisted materials design, could provide valuable insights into interfacial interactions and guide the rational design of next-generation composites.

In conclusion, HAp/MOF and HAp/MXene composites should be viewed as complementary rather than competing material systems. HAp/MOF composites currently demonstrate broader application diversity and a larger body of experimental evidence, whereas HAp/MXene composites provide unique functionalities, particularly high electrical conductivity and photothermal activity, that cannot be achieved with MOF-based systems alone. Continued progress in synthesis, interface engineering, standardized evaluation, and long-term validation will be essential for translating these promising materials from laboratory demonstrations to practical applications in healthcare, environmental technologies, and advanced functional devices.

Author contributions

Mashrafi Bin Mobarak: writing – original draft, writing – review & editing, supervision investigation, data curation, funding acquisition, conceptualization, validation, resources. Md. Rashidul Islam: writing – original draft. Aima Tanjim Khan: writing – original draft. Fatema Nowsin: writing – original draft. Sharita Saha: writing – original draft. Fariha Chowdhury: validation, supervision.

Conflicts of interest

There are no conflicts to declare.

Data availability

No data was used in this review article.