Table 3 Application of functionalized delivery hydrogel scaffolds within the last 5 years

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]