Table 2.

A comparative study on various types of natural compounds incorporated scaffold for tissue engineering application.

Detail of the Scaffold Material	Fabrication Type	Active Medicinal Compound Incorporated	Potential Role, Physicochemical Properties, and the Release Profile of Incorporated Active Medicinal Compound from the Nanobiomaterials	Outcomes
Novel Graphene oxide (GO) and Zn-Curcumin based composite nanofibers	Electrospinning	Curcumin	Core-shell nanofibers (153 nm diameter). Core (Zinc and curcumin complex) and shell (blend of carboxymethyl chitosan, PVA and GO) part of the nanofiber was confirmed through FTIR and XRD analysis. The presence of GO in the blend aided to improve the mechanical properties of nanofibers. In vitro drug release studies were performed for 25 days and revealed that the curcumin release was slower and more prolonged from nanofibers	The synthesized Zn-curcumin composite nanofibers showed excellent support for cell adhesion, spreading and the proliferation process and enhanced the activity of alkaline phosphatase. It has good antibacterial activity and promising potential for bone tissue engineering [174].
Composite nanofibrous scaffold (Curcumin incorporated chitosan, collagen, and polyvinyl-alcohol polymer-based nanofibers)	Electrospinning	Curcumin	The presence of nanometer sized fibers with interconnected pores were confirmed through scanning electron microscopy (SEM) study. An in vitro curcumin release from nanofibers was observed in phosphate-buffered saline (PBS) at 37 °C, which showed that the 20% of initial burst release in 24 h and sustained cumulative curcumin release was slowly increased by almost 90%, observed over a period of 21 days	A biocompatible scaffold used for tissue engineering applications, with well-interconnected pores helping to achieve optimal curcumin release, and increased cell attachment and cell viability. The nanofiber scaffold with curcumin showed higher α-SMA protein expression than the nanofiber scaffold without curcumin [175].
Bifunctional 3D printed scaffold (Liposome encapsulated curcumin onto 3D printed tricalcium phosphate (TCP))	Thin-film hydration	Curcumin	Transmission electron microscope (TEM) study revealed that the curcumin-encapsulated liposomes showed homogenous size distribution in the range of 40–50 nm. The properties of liposomes showed more controlled and sustained drug release of curcumin (17% released in 60 days)	It helps prevent bone cancer cells and promotes healthy bone cells, and this liposome-based, curcumin-loaded, bifunctional, 3D-printed scaffold can be used as a potential substitute to bone graft treatments after tumor removal [176].
3D printed biodegradable scaffolds (Curcumin, polyurethane, and gelatin)	One-step 3D printing process	Curcumin	The surface hydrophilicity, crosslinking density and nanoporous structure of the scaffold facilitated curcumin release. The burst release of curcumin was observed due to the surface hydrophilicity of the synthesized scaffolds.	Hydrophilic biodegradable porous scaffold exhibits excellent cell adhesion and cell proliferation properties. It can be used to regenerate cartilage tissues [177].
Biomimetic nanocomposite scaffolds (Polycaprolactone, Chitosan, Gelatin and Curcumin)	Freeze drying	Curcumin	SEM image revealed that the size of curcumin-loaded nanofibers was 139 nm, whereas the curcumin-free nanofibers were 195 nm. The addition of curcumin significantly reduced the size of the nanofibers. Slow curcumin release was observed in all types of scaffold studied in this work.	It mimics the ECM structure of soft tissues and showed suitable physicochemical and biological properties for skin regeneration [178].
SF-based biofunctional nanofibrous scaffold	Electrospinning method	Aloe vera	The field emission SEM study revealed the average size fiber diameter of Aloe-vera-loaded nanofiber was in the range of 212 ± 27 nm. The successful incorporation of aloe compound in the scaffold was confirmed through FTIR study.	The biological responses of the synthesized nanofibrous scaffolds, such as cell adhesion and migration, have been evaluated, and they provide a stable environment in the growth of human dermal fibroblasts for skin tissue engineering applications [179].
Polycaprolactone, chitosan and Aloe vera (AV) blended nanofiber membranes	Electrospinning method	Aloe vera	2% of AV plays an important role in the size of the nanofibers diameters, making it not easy to break. The average size diameter of nanofibers was 37.58 ± 3.24 (sloping free surface electrospinning method) and 53.63 ± 12.31 (modified bubble electrospinning method)	It has shown enhanced antibacterial activity against E. coli and S. aureus and Cytocompatibility against human umbilical vein endothelial cells. It is suiSection for treating acute wounds [180].
Alginate based hydrogel	Solvent-casting process	Aloe vera	The chemical composition of AV existence in the hydrogel was confirmed through FTIR study and thermogravimetric analysis results showed that the presence of AV increased the thermal stability of the material.	The synthesized films were evaluated with different physical and mechanical properties and could be applied for skin applications. The loading efficiency of Aloe vera was greatly increased due to the water absorption and swelling behavior of the hydrogel film [181].
Biodegradable soybean-based biomaterial	Thermosetting	Soybean	Genistein isoflavones from soybean could stimulate protein synthesis and osteoblastic functions and it plays a major role in bone regeneration (in vivo). The degradation of soybean granules was observed in the periphery of the defects through polarized light microscopy.	An in vivo rabbit study confirmed the osteogenic potential of the soybean-based biomaterial as a bone filler for bone regeneration [182].
Soybean-based biomaterial granules	Simple thermosetting method	Soybean	Genistein is one of the soy isoflavones present in the soybean. Approximately 0.08 µg/mL genistein release was observed after 100 h of the study in PBS pH 7.4 at 37 °C	An in vitro study has revealed that it reduced the activity of macrophages, differentiates osteoblast and may be functionally used for bone regeneration [183].
Multifunctional 3D printed TCP scaffolds	Binder jetting technique	Soy isoflavones	The multifunctional scaffold was prepared using all the three soy isoflavones in the ratio of 5:4:1 (genistein, daidzein and glycitein) and the release of all three isoflavones were observed in both pH 7.4 and 5.0 for 16 days. It revealed that 72.5% (genistein), 100% (daidzein) and 13.75% (glycitein) release in pH 7.4 and 25.1% (genistein), 23.3% (daidzein) and 2.97% (glycitein) release in acidic pH 5.0	It may be used in postsurgical applications, which include bone graft substitutes, drug delivery vehicle, localized tumor cell suppression and bone cell proliferation. The scaffolds must be tested with other malignant cell lines to confirm their chemopreventive efficacy and characterizations related to the expression of different bone markers [184].