Table 2.

Indicative examples of mammalian, marine and recombinant collagen type II scaffolds in preclinical models. Abbreviations: 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-sulfo-N-hydroxy-succinimide: EDC-NHS; Adipose derived stem cells: ADSCs; Chondroitin sulphate: CS; Dehydrothermal: DHT; Bone marrow stem cells: BMSCs; Glycosaminoglycan: GAG; Osteoarthritis: OA; Ultraviolet irradiation: UV

Scaffold conformation	Model, Major findings, Reference
Bovine collagen type II, cadherin 11 and recombinant fibronectin spongesGlutaraldehyde crosslinkedRabbit BMSCs	Rabbit chondral defectThe cell loaded scaffold induced cartilage formation 12 weeks post-surgery [213]
Bovine collagen type II and CS spongesGenipin crosslinkedRabbit BMSCs	Rabbit chondral defectLacuna formation 4 weeks post-surgery and high collagen type II and aggrecan and low collagen type I gene expression 24 weeks post-surgery [214]
Bovine collagen type I and collagen type II and CS spongesCarbodiimide crosslinkedNo cells	Rabbit chondral defectCollagen type I scaffolds attracted progenitor cells into the defect and induced fibro-cartilage repair, whilst collagen type II scaffolds attracted less cells into the defected, but the invaded cells adopted a chondrogenic phenotype and increased the amount of superficial cartilage-like tissue 12 weeks post-surgery [188]
Bovine collagen type II hydrogelsPentaerythritol polyethylene glycol ether tetrasuccinimidyl glutarate crosslinkedRabbit chondrocytes	Rabbit chondral defectCartilage repair was improved in cell-scaffold treated groups and collagen type I was not detected 24 weeks post-surgery [215]
Bovine collagen type II spongesGenipin crosslinkedRabbit BMSCs	Rabbit osteochondral defectThe implanted cells became chondrocytes in the implanted area and cartilage structure, same as normal cartilage, was observed in the repair site 24 weeks post-surgery [216]
Porcine collagen type I, collagen type II and collagen type III blend spongesNo crosslinkerAutologous ovine chondrocytes	Ovine chondral defectScaffolds with chondrocytes and with microfracture into the subchondral plate resulted in hyaline-like cartilage regeneration 16 weeks post-surgery [217]
Porcine collagen type II spongesEDC-NHS crosslinkedAutologous chondrocytes	Canine chondral defectScaffolds cultured with chondrocytes for 4 weeks prior implantation increased the amount of reparative hyaline cartilage tissue after 15 weeks [200]
Porcine collagen type II or Arg-Gly-Asp sequence with poly(L-lactide) or poly(D,L-lactide-co-glycolide) spongesCarbodiimide crosslinkedRabbit chondrocytes	Rabbit chondral defectCollagen type II prevented infiltration by host tissue and capsule formation, showed no inflammation and resulted in partial or full repair with equal cellularity and 75-80% matrix contents of a normal rabbit articular cartilage 8 weeks post-surgery [218]
Porcine collagen type II sponges and filmsUV crosslinkedAutologous canine chondrocytes	Canine chondral defectTotal defect filling ranged 56-86%, with the greatest amount found in scaffolds with cells and microfracture compared to scaffolds alone with microfracture and microfracture alone 15 weeks post-surgery, the tissue filling the defect was predominantly fibrocartilage [199]
Porcine collagen type II spongesNo crosslinkerNo cells	Rabbit chondral defectScaffolds displayed quicker effusion absorption, greater newly formed cartilage-like areas than the empty group 18 weeks post-surgery, sporadic cartilage signals first appeared at 6 weeks in the scaffolds [219]
Collagen type II hydrogelsNo crosslinkerRabbit chondrocytes	Rabbit osteochondral defectCells seeded collagen type II hydrogels displayed better cartilage repair compared to sham, cell pellet and scaffolds alone groups [212]
Collagen type II-GAG sponges reconstituted from porcine cartilage and bovine collagen type I sponges with shark CSDHT and UV crosslinkedAutologous canine chondrocytes	Canine chondral defectBoth cell-seeded scaffolds exhibited comparable cartilage regeneration potential and increased cartilaginous tissue in chondral defects and adjacent subchondral bone space compared to empty group 15 weeks post-surgery [189]
Chicken collagen type II and fibrin sealant hydrogelsNo crosslinkerHuman ADSCs	Rabbit chondral defectImproved overall repair of chondral defects, cellular organisation and collagen fibre alignment 12 weeks post-surgery [220]
Chicken collagen type II and rat collagen type I blend hydrogelsNo crosslinkerAutologous rabbit BMSCs	Rabbit chondral defectCell-seeded collagen type I/II scaffolds exhibited better cartilage repair outcomes in trochlear groove defects compared to pure collagen type I hydrogels and empty chondral defects 13 weeks post-surgery [187]
Squid collagen type II intra-articular injectionNo crosslinkerNo cells	Suppressed pro-inflammatory macrophage phenotype, prevented hypertrophic chondrocyte phenotype and alleviated inflammation in an OA rat model 6 weeks after OA induction [134]
Shark collagen type II was administered orallyNo crosslinkerNo cells	Facilitated recovery of articular membranes in the ankle joint and suppressed rheumatoid arthritis in a complete Freund's adjuvant-induced rheumatoid arthritis rat model 2 weeks after rheumatoid arthritis induction [221]
Recombinant collagen type II hydrogelsNo crosslinkerAutologous rabbit chondrocytes	Rabbit osteochondral defectCell-scaffold treated group exhibited a slight but insignificant improvement in cartilage repair compared to spontaneous repair group and both groups had lower modified O'Driscoll's score than intact cartilage 24 weeks post-surgery [222]
Recombinant collagen type II and polylactide spongesCarbodiimide crosslinkedAutologous porcine chondrocytes	Porcine chondral defectHyaline cartilage formed most frequently in the recombinant collagen type II / polylactide / cells group, which also improved biomechanically properties only over the spontaneous repair group and showed less adverse subchondral reactions than the Chondro-Gide® (a bilayer collagen type I / collagen type III membrane) / cells group, but not in comparison to the spontaneous repair group 16 weeks post-surgery [190]