Table 3.

Application of functionalized delivery hydrogel scaffolds within the last 5 years

Scaffold type	Description	Scaffold materials	Supplementation	Manufacturing process	Effects	Reference
Single-layer hydrogel	Homogeneous hydroxyapatite/alginate composite hydrogel	Alginate	Hydroxyapatite, sodium citrate	3D Bioprinting	ALG/HAP hydrogel stimulated chondrocytes to secrete calcified matrix in vitro and in vivo	[75]
	Decellularized cartilage ECM and PEGDA integrated hydrogel	Polyethylene glycol diacrylate	Honokiol, chondrocyte-derived ECM	3D Bioprinting	The decellularized cartilage PEGDA/ ECM hydrogel effectively promoted regeneration of hyaline cartilage and subchondral bone tissues in osteochondral defect model of rabbits	[76]
	3D-printed PRP-GelMA hydrogel	Gelatin methacryloyl	Platelet-rich plasma	3D Bioprinting	The 3D-printed PRP-GelMA hydrogel promoted osteochondral repair through immune regulation by M2 polarization in osteochondral defect model of rabbits	[77]
	Multifunctional polyphenol-based silk hydrogel	Silk fibroin	E7 (EPLQLKM), tannic acid	Chemical and physical crosslinking	The SF-TA-E7 hydrogels promoted enhanced regeneration of both cartilage and subchondral bone in osteochondral cylindrical defects model of rabbits	[78]
	Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel	Porous chitosan, hydroxypropyl chitin	Kartogenin, dimethyloxallyl glycine	Chemical and physical crosslinking	The immunomodulation-based CSK-PMS hydrogel effectively created M2 macrophage microenvironment and orchestrated osteochondral regeneration in the osteochondral defect model of rats	[73]
Multilayer hydrogel	Biomimetic bacterial cellulose-enhanced double-network hydrogel	γ-glutamic acid, lysine, alginate, bacterial cellulose	Hydroxyapatite	Chemical and physical crosslinking	Synthesized scaffolds led to good integration between the neo-subchondral bone and the surrounding host bone in osteochondral defect model of rabbits	[79]
	Injectable BRH-CRH biphasic hydrogel	Hyaluronic acid methacryloyl, Gel methacryloyl, isocyanatoethyl acrylate-modified β- cyclodextrin	Kartogenin, melatonin	Photopolymerization	BRH-CRH biphasic hydrogel significantly promoted the simultaneous cartilage regeneration and bone regeneration to achieve osteochondral defect repair in osteochondral interface defect rabbit model	[80]
	Enzymatically crosslinked silk fibroin (SF)-Laponite (LAP) nanocomposite hydrogel	Silk fibroin	Laponite	Chemical crosslinking	The SF-LAP hydrogel promoted osteogenic and chondrogenic differentiation of BMSCs and facilitated enhanced regeneration of cartilage and subchondral bone in rabbit full- thickness osteochondral defects	[81]
	GelMA and GelMA-HAp bilayered porous hydrogel scaffolds	Gelatin methacryloyl	Hydroxyapatite	3D Bioprinting	The GelMA/GelMA-HAp bilayered porous scaffolds promoted the regeneration of articular cartilage in a rabbit trochlea model	[71]
	TGF-β loaded photo cross-linked hyaluronic acid hydrogel	Methoxy poly (ethylene glycol), poly (β-caprolactone)	Hydroxyapatite, RGD peptide, TGF-β1	Photopolymerization	The UV light-cured hyaluronic acid hydrogel containing growth factor TGF-β1 could enhance the healing of the osteochondral defect in the knees of rabbits	[82]
	Bilayered hydrogel scaffold loaded with KGN and P24 peptides	Gelatin, silk fibroin, oxidized dextran, poly (L-lactic acid), poly (Lactic-co-glycolic acid), poly(ε-caprolactone)	Kartogenin, bone morphogenetic protein—2	Chemical crosslinking	The bilayered scaffold loaded with KGN and P24 peptides significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model	[83]
	Integral bilayer silk scaffold consisting of a dense, smooth, biomimetic cartilage layer and a BMP-2-loaded porous layer combined with TGF-β3/Sil-MA	Methacrylated silk fibroin	TGF-β3, bone morphogenetic protein—2	Photopolymerization	The TGF-β3-loaded Sil-MA hydrogel guided new cartilage to grow towards and replace the degraded cartilage layer from the surrounding native cartilage in the early stage of knee repair	[74]
Gradient hydrogel	Biodegradable preprogrammed biohybrid gradient PACG-GelMA hydrogel scaffolds	Cleavable poly (N-acryloyl 2-glycine), methacrylated gelatin	Bioactive manganese ions, bioactive glass	Photopolymerization	The resultant biohybrid gradient hydrogel scaffold promoted cartilage and subchondral bone repair in rat knee osteochondral defect	[29]
	Hybridizing gellan/alginate and thixotropic magnesium phosphate-based hydrogel scaffolds	Alginate sodium, gellan gum	Magnesium	Chemical and physical crosslinking	The SA-GG/TMP-BG hydrogel scaffolds induced subchondral bone repairing and promoted the cartilage reconstruction in vivo rabbit cartilage defect model implantation	[33]
	Gradient nano-engineered in situ forming composite	Alginate, poly (vinyl alcohol)	Nanohydroxyapatite, glycosaminoglycan	Chemical crosslinking	The nanoengineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration in model of rabbits	[30]