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. 2023 Jun 27;15(7):1836. doi: 10.3390/pharmaceutics15071836

Table 1.

Research pattern for cryogel materials used in pharmaceutical and biomedical applications.

Alginate-Based Cryogel
Material Used Main Outcomes Ref.
Alginate cryogel loaded with chemoimmunotherapy drug-loaded nanoparticles Sp-AcDEX NPs and Nutlin-3a Chemoimmunotherapy drug delivery system for cancer treatment, enhancing accumulation of Sp-AcDEX NPs in tumor tissue and inducing immunogenic cell death with Nutlin-3a [26]
Macroporous alginate cryogel incorporated with gold nanorods (GNRs) Controlled drug delivery system for Mitoxantrone with on-demand release through near-infrared irradiation, suppressing tumor growth in vivo [27,28]
Nanocomposite hydrogel formed by bio-orthogonal crosslinking of alginate using tetrazine-norbornene coupling and pre-adsorbed charged Laponite nanoparticles Sustained, bioactive release of therapeutic proteins with precise tuning of release kinetics, simplifying the design of hydrogel drug delivery systems [27,28]
Sodium alginate-based aerogel with photosensitizers and phenylboronic acid Antibacterial photodynamic wound dressing with improved solubility, hemostasis capacity, and antibacterial activity against Staphylococcus aureus [29]
Alginate and carboxymethyl-cellulose-based cryogel neural scaffold Injectable surgical scaffold for minimally invasive delivery of an extended living neuronal network, with high local Young’s modulus for neuronal network protection and soft macroscopic scale for easy injection [30,31,32]
3D porous scaffold made from carrageenan and alginate with EDC/NHS cross-linker Scaffold with a porous and interconnected structure, good physical and mechanical stability, higher cell attachment, better cellular response, and higher metabolic activity than matrices with other cross-linkers [31,32]
Autoclavable cryogels made from several naturally derived polymeric precursors (alginate, hyaluronic acid, and gelatin) Maintain their structural and physical properties, including their syringe injectability signature, after autoclave sterilization [31,32]
Chitosan-Based Cryogel
Material Used Main Outcomes Ref.
Hydrophobically modified chitosan cryogel Potential material for controlled drug delivery applications [33]
Chitosan aerogel microparticles Suitable for pulmonary drug delivery systems; effects of chitosan molecular weight, polymer concentration, and tripolyphosphate concentration on drug release were investigated [34]
Chitosan sponges Cross-linked with glutaraldehyde It possesses antibacterial, antioxidant, and controlled delivery properties for plant-derived polyphenols, showed remarkable shape recovery, good radical scavenging activity, and strong antibacterial properties against both Gram-positive and Gram-negative strains [35]
Cryogel–microparticle composite with polymeric network and microstructured biocompatible pore surface Incorporating microparticles (MPs) into the polymeric network of cryogels to deliver bioactive molecules, demonstrated good biocompatibility with the growth of various cell lines, potential for delivering bioactive/drug molecules to cells growing in 3D conditions [36]
Double cryogel system, gelatin/chitosan cryogel (GC) surrounded by Gelatin/heparin cryogel (GH) The double cryogel system (DC) is used for dual drug delivery with different release kinetics to induce bone regeneration. The GH layer loaded with VEGF induces initial release, while the GC layer loaded with BMP-4 induces sustained release. [37]
Chitosan and nanofibrillated cellulose hydrogel Investigated as a biomaterial membrane for peripheral nerve regeneration due to its mechanical strength, thermal resistance, slow rate of swelling, and non-toxicity to Schwann cells. Used in vivo with autologous implant to promote functional recovery within 15 days. [38]
Chitosan-clinoptilolite 3D biocomposites Investigated for their potential as drug carriers. Biocomposites with higher content of clinoptilolite were found to have a more ordered porous structure and lower water uptake. Effective drug release was observed in phosphate buffer saline, suggesting potential for drug delivery systems. [39]
Pectin/Chitosan Composite Cryogel Potential candidate for biomedical applications due to improved mechanical strength, surface morphology, degradation time, adhesion to biological tissues, and biocompatibility. [40]
Poly(N-isopropylacrylamide) scaffold loaded with chitosan/bemiparin nanoparticles Used for tissue engineering and controlled release of heparin. Cryogel exhibits a highly porous structure, is non-cytotoxic, and exhibits excellent properties for application in tissue engineering. [41]
Chitosan/Hydroxyapatite/Heparin/PVA Composite Cryogel Scaffold Potential for bone regeneration and tissue engineering applications, as it efficiently immobilizes BMP-2 and supports differentiation of bone marrow mesenchymal stem cells into the osteogenic lineage. [42,43]
Thiolated Chitosan/Oxidized Dextran/Locust Bean Gum Semi-IPN Cryogel Promising candidate for use as a hemostatic dressing due to its improved mechanical strength, decreased hydrophobicity, increased swelling ratio, and enhanced hemostatic properties. Cryogel also exhibits good cytocompatibility, blood compatibility, and hemostatic potential. [42,43]
Chitosan-graft-poly(N-isopropyl acrylamide)/PVA Development of a smart polymeric vehicle for antifungal drug delivery for mucosal applications and various parameters of cryogels were also characterized. [44]
Chitosan/2-hydroxyethylcellulose cryogel Development of a pH-sensitive cryogel for drug delivery applications. The cryogels were characterized for physico-mechanical properties and bioadhesive properties. [45]
Methacrylated chitosan/chondroitin sulfate cryogel microparticle (CMP) system Development of an injectable CMP system for growth factor delivery in tissue regeneration applications. The cryogel microparticles were characterized for in vitro and in vivo neovascularization using rhVEGF. [46]
Chitosan-based polyelectrolyte complex cryogels Development of a sustainable strategy to fabricate drug delivery systems using polyelectrolyte complex cryogels physically stabilized by spontaneous interactions. The cryogels were characterized for their structure, morphology, and drug release properties. [47]
Glutaraldehyde-crosslinked chitosan cryogels Fabricated with superamphiphilicity and high separation efficiency for various surfactant-stabilized oil-in-water emulsions under continuous flow mode, make them promising for applications in separation processes driven by gravity or a peristaltic pump. [151]
Colloidal chitosan/k-carrageenan/carboxymethylcellulose sodium salt cryogel Encapsulation of curcumin in a controlled release system. [152]
Chitosan/xanthan gum polyelectrolyte complex (PEC) aerogel Development of bone-like structured aerogels suitable for biomedical and environmental applications. [48]
Chitosan/citric acid/silver nanoparticle cryogel Development of a shape memory cryogel dressing for skin wounds, promoting hemostasis, blood cell adhesion, and wound healing. [49,50]
Chitosan and gluconic acid conjugate cryogels Development of physically crosslinked chitosan cryogels as practical wound dressings, which retained the same biological properties as the pre-autoclaved ones and showed enhanced resistance to enzymatic degradation. [49,50]
Methacrylic acid/acrylamide or 2-hydroxyethyl methacrylate cryogel 1st network crosslinked with chitosan/poly(ethyleneglycol) diglycidyl ether 2nd network Used for designing macroporous hydrogels for controlled release of macromolecular drugs [51]
Chitosan/silk fibroin/tannic acid/ferric ion cryogel Developed as a wound dressing with stimuli-responsive photothermal therapy and good antibacterial and cell-proliferative properties [49,50,52]
Chitosan-gelatin-chondroitin sulfate/nano-hydroxyapatite-gelatin cryogel scaffold Used for tissue-engineering repair of articular cartilage injuries with potential therapeutic approaches for osteochondral repair [21]
Chitosan-gelatin-polypyrrole 3D scaffolds with chitosan and gelatin microspheres Evaluated for delivering alpha-ketoglutarate (alpha-KG) to cells in tissue engineering applications [53]
Gelatin-Based Cryogel
Material Used Main Outcomes Ref.
Gelatin-based cryogel system embedded with CaCO3 microspheres and ciprofloxacin hydrochloride Address the condition of osteomyelitis and osteoporosis, sustained drug release for up to 21 days, significant increase in cell viability and alkaline phosphatase levels in rat osteoblasts [54]
Injectable 3D microscale cellular niches using biodegradable gelatin microcryogels Optimize cell therapy for damaged tissues or organs, facilitate cell protection during injection and in vivo cell retention, survival, and therapeutic functions, superior therapeutic efficacy for treating critical limb ischemia in mouse models [59]
Gelatin microcryogels loaded with hASCs Injectable gelatin microcryogels were loaded and primed with human adipose-derived stem cells to create 3D cellular micro-niches that accelerate wound healing. [60]
Injectable cryogels made of gelatin methacryloyl and poly(ethylene)glycol Tunable degradability and porosity suitable for cell and drug delivery applications. [56]
Cryogel scaffold composed of gelatin Evaluation of polyelectrolyte multilayer microcapsules for controlled release of transforming growth factor-beta 1 (TGF-beta 1) in gelatin-based hydrogels and cryogel scaffolds for tissue engineering applications. [57]
Gelatin-based cryogel with cellulose nanocrystal (CNC) and poly-amidoamine (PAMAM) dendrimer For sustained drug release and improved mechanical properties. [58]
Cryogenic Gelatin-Hyaluronic Acid Composite Elastic scaffold for 3D bioprinting with continuous interconnected macroporous structure, allowing for cell attachment, viability, and proliferation [61]
Nanocellulose and Gelatin Composite Cryogel Controlled drug release carrier with controllable and sustained release of drug 5-FU [62]
Nanosilicate and gelatin methacrylate Cryogel Tough, macroporous hydrogel for drug delivery with sustained release under physiological conditions, reducing endothelial cell injury caused by nutrient deprivation [63]
Gelatin/ascorbic acid (AA) cryogels Carriers for corneal keratocyte growth in corneal stromal tissue engineering [64]
Gelatin/heparin cryogel and BMP-2-loaded cryoelectrospun poly(epsilon-caprolactone) hybrid scaffold Bone regeneration scaffold with enhanced mechanical support and sustained release of BMP-2 [66]
Gelatin and heparin-based injectable cryogel Carrier for in vivo cell and growth factor delivery in hindlimb ischemic disease [67]
Amino acid-based functional monomer with HEMA and gelatin Development of degradable molecularly imprinted cryogel for pH-responsive delivery of doxorubicin [65]
Usnic acid encapsulated in Rhamnolipid biosurfactant nanoparticles enriched cryogel nanocomposite scaffold Design of cryogel nanocomposite scaffold with dual properties of bone regeneration and antibacterial effect for the treatment of osteomyelitis [55]
Macroporous composite biomaterial of gelatin-hydroxyapatite-calcium sulphate Development of biomaterial with spatio-temporal delivery of rhBMP-2 and ZA leading to increased bone formation compared to commercially available carriers [68]
Gelatin-based cryogel Use of gene delivery and tissue-engineering approaches for regenerating cartilage tissue lost due to trauma, tumor surgery, or congenital defects [69]
Polysaccharides and Their Hybrids-Based Cryogel
Material Used Main Outcomes Ref.
Hydrophobically modified agarose cryogels (HMA cryogels) Drug delivery systems, low cytotoxicity, adsorb more hydrophobic dye, and controlled release of dye [75]
Mesophyll-inspired agarose cryogel (MAC) Component of leaf-inspired micropump (LIM) for smart microfluidic applications, adjusts delivery rate of therapeutic liquid in response to temperature changes [76]
Agarose-based cryogels, including cellulose fibers and microparticles Water absorption and retention ability with high structural stability, potential for drug delivery devices [77,78]
Carrageenan cryogels loaded with alpha-aminophosphonates Improved mechanical properties and sustainable release of antimicrobial compounds for potential use against S. aureus [79]
Kappa-Carrageenan (kappaC) matrix Transdermal controlled delivery patch for Metformin, with enhanced drug release-permeation and diffusion coefficients when an electrical potential is applied [80]
LBG, XG, and MG-based cryogel scaffolds Promising properties for cartilage and soft tissue engineering and drug delivery, sustained release of Kartogenin achieved [81]
Cellulose cryogels microsphere For wound healing, tissue regeneration, and drug delivery [22,82]
CNF-PNIPAm hybrid Synthesized temperature-sensitive polymer-modified cellulose nanofibril (CNF) cryogel microspheres with potential application in controlled drug release. [83]
Biopolymer cryogels Developed as an effective delivery system for curcumin in the form of Curcumin-nanostructured lipid carrier-loaded oleogels (Cur-NLC-OGs). Biopolymer cryogels were used to stabilize and self-stand the Cur-OGs. [84]
Super-macroporous hydroxypropyl cellulose (HPC) cryogels embedded with stabilized core-shell micelles (SPM) For sustained delivery of poorly water-soluble drugs [153]
Hydroxyethyl cellulose (HEC) cryogels with polymeric micelles Sustained topical delivery of hydrophobic natural substances such as cannabidiol [85]
Composite cryogels (PVP/NaCMC) microspheres loaded with Mupirocin (MP) Controlled release of antibiotic Mupirocin [86]
Enzymatically modified starch cryogels Carriers of active molecules for drug delivery systems and potential applications in biomedical and food packaging scenarios [154]
Composite cryogels (OPS or OWS with DMAEM) fabrication of semi-IPN cryogels using N,N-dimethylaminoethyl methacrylate (DMAEM) and oxidized starches oxidized potato starch (OPS) or oxidized wheat starch (OWS) For controlled drug release in simulated gastric fluid at pH 1.3 [155]
PEG Derivative-Based Cryogel
Material Used Main Outcomes Ref.
Poly(ethylene glycol)-heparin cryogel scaffold Promotes proliferation and survival of bsAb-releasing-MSCs, constant release of sustained and detectable levels of bsAb, and effective in triggering T-cell-mediated anti-tumor responses for treatment of acute myeloid leukemia (AML) [87]
Activated carbonate group- with PEG functionalized cryogels Slow-releasing drug reservoirs for anticancer drug delivery, with 7-fold higher drug release compared to hydrogels [23]
Poly(ethylene glycol) diacrylate and maleimide-functionalized heparin cryogels Sustained delivery of growth factors for tissue engineering and regenerative medicine applications, with the ability to load and release nerve growth factor over a period of 2 weeks and induce neurite outgrowth [88]
Dextran methacrylate and polyethylene glycol dimethacrylate cryogel Spongy scaffold for promoting the delivery of biomolecules in drug delivery and tissue engineering applications, with improved swelling, increased interconnected porosity, and higher mechanical resistance than conventional hydrogels [142]
StarPEG-heparin cryogel Allows for tunable, long-term delivery of different signaling proteins for tissue engineering applications, inducing local differences in protein concentration, and inducing neuronal differentiation of cells [24]
Dendrimer cryogel made of hyperbranched amine-terminated polyamidoamine (PAMAM) dendrimer G4.0 and linear polyethylene glycol (PEG) diacrylate Superelastic network with high compression elasticity, super resilience, and stability at acidic pH, suitable for biomedical applications due to its self-triggered degradation at physiological pH [156]
Poly(ethylene glycol) diacrylate microcryogels Utilized in a syringe-based 3D culture system for the mechanical preconditioning of mesenchymal stromal/stem cells toward nucleus pulposus (NP)-like cells, with potential for NP regeneration [89]
PVOH-Based Cryogel
Material Used Main Outcomes Ref.
PVA/ZnO/FA nanocomposite Drug delivery application with controlled release of fulvic acid [90]
PVA cryogel with thermochromic ink Thermochromic material for temperature estimation in ultrasound therapy [91]
PVA cryogel Enhancing solubility of Simvastatin for use as a prolonged-release cryogel matrix for hydrophobic drugs and potential biomaterial for tissue engineering [92,143]
Poly(vinyl) alcohol and propylene glycol cryogel Used as a hydrophilic active wound dressing loaded with trans-resveratrol for controlled release and reduced irritation [144]
Composite cryogels containing PVA particle and porous adsorbent particles Used for capturing glycoproteins and evaluated for repeated use in batch and chromatographic experiments [145]
Polyvinyl alcohol cryogel with high-methoxylated pectin Used for the controlled release of the antibiotic enrofloxacin, and a two-layer film system was designed to modulate the release rate of the drug [146]
Polyvinyl alcohol cryogel with urea additives Used as a polymeric carrier in drug delivery systems with widened macropores, and the release rate of the drug depends on the urea content in the initial PVA solution [147]
Highly porous composite PVA cryogels loaded with drug molecule Highly porous composite cryogels loaded with PHB microbeads containing simvastatin for controlled drug delivery [93]
PVA/iron oxide NPs Cryogels for thermally triggered drug release based on shape-selective heat transfer using magnetic nanoparticles coated with acetaminophen [148]
Polyvinyl alcohol (PVA) Investigation of PVA cryogel for iontophoretic transdermal drug delivery [94,149]
PVA and its nanocomposites Used for biomedical and medical device applications due to its unique mechanical properties that can be tailored to match soft tissues [96]
PVA-NLC, nanostructured lipid carriers loaded with drug molecules Serves as an adhesive film that contains nanostructured lipid carriers loaded with olanzapine and simvastatin for transdermal treatment of psychiatric disorders [95]
PVA-DNA gel matrices Examines factors that affect the release rate of deoxyribonucleic acid (DNA) from PVA hydrogels and its blend with DNA. Investigates the potential of designing controlled DNA release PVA-based devices [97,98]
PVOH Derivatives-Based Cryogel
Material Used Main Outcomes Ref.
Molecularly imprinted cryogel Used for solid-phase extraction of propranolol from aqueous solution and complex plasma sample due to its high selectivity and stability [99]
PVA and gelatin cryogels Evaluated for their water-uptake potential, influence of various factors on water sorption, and biocompatibility for potential use in biomedical applications [100]
PVA and egg albumin cryogels Investigated for their water sorption capacity, swelling behavior, in vitro biocompatibility, thermal and morphological characterization for potential use in the biomedical field [101]
pH-sensitive hydrogel made from a blend of polyvinyl-alcohol, polyacrylic acid, and synthetic hydroxyapatite Explored for specific drug delivery applications due to their smart properties. Investigated the effects of hydroxyapatite on mechanical strength, bioactivity, and drug release profiles, with promising results seen in terms of swelling, gel fraction, and drug delivery [102]
Gum tragacanth-polyvinyl alcohol (GT-PVA) cryo- and xerogels Prepared and evaluated for their physical, mechanical, and release properties, including the effect of GT ratio and inclusion of silymarin. Found to have potential applications due to their porosity, microstructure, and mucoadhesive properties [157]
poly(vinyl alcohol),pullulan and zeolite Composite cryogel Controlled release of Enalapril Maleate drug used to treat hypertension and heart failure [104]
Dual network hydrogel of poly(vinyl alcohol) cryogel and sodium alginate Synthesized for potential biomedical applications. Can absorb and retain fluids, incorporate biological molecules/drugs [105]
PVA and polyacrylic acid Cryogel carrier system Controls the release rate of extracted propolis for enhanced efficacy. Can be used as bactericidal dressing [106]
Two-phase hydrogel prepared by physically imbedding a xerogel in the core of a cryogel that was freeze thawed with PVA and PAA Temperature-sensitive drug delivery systems, drug release at a slower rate from hydrogels containing acrylic acid [158]
PVA/HA pH-responsive cryogel Drug delivery system for the treatment of psoriasis, significant decrease in toxicity, swelling and drug release at pH 5.5 [103]
Acrylate and Methacrylate Base Cryogel
Material Used Main Outcomes Ref.
NIPA and HEMA-lactate-Dextran-based biodegradable and thermoresponsive cryogels Potential use in bone tissue engineering with controlled drug release capabilities [107]
Poly 2-hydroxyethyl methacrylate (pHEMA) and halloysite nanotubes (HNTs) embedded with thymol (Thy) Sustained release drug delivery system for wound healing in space [25]
Poly(2-hydroxyethyl methacrylate) Purification of plasmid expressing Influenza hemagglutinin gene [108]
Metal-chelate monomer N-methacryloyl-L-histidine, hydroxyethyl methacrylate and Cu(2+) ion Imprinted cryogel discs for delivering chemotherapy drug 5-fluorouracil (5-FU) [109]
Cryogel-based molecularly imprinted membranes Implantable drug delivery system for controlled release of antineoplastic agent Mitomycin C for cancer treatment [110]
HEMA-based cryogels Potential candidates for controlled drug delivery systems in biomedical applications [150]
Polymeric cryogels Efficient removal of emerging contaminants from water and suitable for drug delivery applications [111]
Poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) cryogel Suitable anticancer drug delivery carrier [112]
PETEGA cryogels Controlled drug release for verapamil hydrochloride [113]
Terpolymer hydrogels and cryogels Potential to improve loading capacity of polymers used in anticancer drug delivery systems [114]
Other Cryogels
Material Used Main Outcomes Ref.
Poly(N-isopropylacrylamide) cryogels with conducting polyaniline or polypyrrole nanoparticles Potential application in electrical devices, tissue engineering scaffolds, drug delivery vehicle, and electronic skin [115]
Zwitterionic cryogels For drug delivery, chemoimmunotherapy, and long-term release of proteins [119,120,121]
Calcium phosphate-based cryogel encapsulating alkaline phosphatase (ALP) Preserves activity of ALP and has chemical and structural properties determined using X-ray diffraction, helium pycnometry and mercury porosimetry [129]
Furan-based cryogel (CG) scaffold covalently conjugated with maleimide-modified antimicrobial peptides Rapid loading and release of therapeutic peptides with high water uptake; “on-demand” photothermal heating upon NIR irradiation [131]
Hybrid and composite biomaterials To enhance mechanical strength and porosity [126,130,135]