Table 1.

Indicative examples of mammalian, marine and recombinant collagen type II scaffolds that have been shown to maintain and/or induce chondrogenic phenotype in vitro. Abbreviations: 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-sulfo-N-hydroxy-succinimide: EDC-NHS; Adipose derived stem cells: ADSCs; Bone marrow stem cells: BMSCs; Cartilage oligomeric matrix protein: COMP; Chondroitin sulphate: CS; Dehydrothermal: DHT; Extracellular matrix: ECM; Fibroblast growth. factor: FGF; Glycosaminoglycan: GAG; Hyaluronan: HA; Insulin-like growth factor: IGF; Matrix metalloproteinase: MMP; Proteoglycan: PG; Sex-determining region Y-type box transcription factor 9: SOX9; Ultraviolet irradiation: UV.

Scaffold conformation	Major findings, Reference
Bovine collagen type II, CS and HA spongesGenipin crosslinkedHuman chondrocytes	Chondrocytes maintained round morphology after 14 days of culture. Increased gene expression of aggrecan, collagen type II and COMP and greater accumulation of PGs was seen on scaffolds with CS and HA than those without CS and HA [161]
Bovine collagen type II spongesGenipin crosslinkedHuman chondrocytes	The administration of GAGs to culture medium improved cell differentiation tendency to functional hyaline cartilage, as evidenced by the upregulation of GAG biosynthesis rate and gene expression of aggrecan and collagen type II after 28 days of culture [201]
Bovine collagen type II and CS spongesNo crosslinkerHuman BMSCs	The cells produced abundant collagen type II on type II scaffolds and collagen type I on type I scaffolds. The addition of CS upregulated the gene expression of collagen type II, compared to type I and type II alone scaffolds [175]
Bovine collagen type II and CS spongesEDC-NHS crosslinkedBovine chondrocytes	Chondrocytes maintained round morphology, the cells loaded scaffolds were surfaced with a cartilaginous-like layer and collagen type II scaffolds contained occasionally clusters of cells inside the sponges in contrast to collagen type I sponges after 14 days of culture [202]
Bovine collagen type II spongesUV crosslinkedMurine chondrocytes	The primary chondrocytes in the scaffolds maintained chondrogenic phenotype after 3 weeks of culture. The gene expression of collagen type II, collagen type XI, and SOX9 in de-differentiated chondrocytes cultured in the scaffolds decreased when compared to that in primary chondrocytes after 4 weeks of culture [203]
Bovine collagen type II coated chitosan fibresPolyglycolic acid mesh was used as a reference groupNo crosslinkerMurine BMSCs	The cell number, the matrix production (dry weight, GAG quantifications), and the chondrogenic marker gene expression (aggrecan, collagen type II) were upregulated in collagen type II coated chitosan scaffolds compared to pure chitosan scaffolds and polyglycolic acid scaffolds after 21 days of culture [165]
Porcine collagen type II hydrogelsNo crosslinkerRabbit chondrocytes	Chondrocytes maintained chondrogenic phenotype and the cell density gradient distribution resulted in a ECM gradient distribution in the scaffolds after 3 weeks of culture [172]
Porcine collagen type II and CS hydrogelsEDC-NHS crosslinkedRabbit chondrocytes	Chondrocytes maintained round morphology, the collagen fibres became thicker and arranged neatly with the increase of CS in the scaffolds and displayed periodic alternation of light and shade after 7 days of culture [176]
Porcine collagen type II and GAG sheetsDHT and carbodiimide crosslinkedCanine chondrocytes	The addition of 5 ng/ml FGF-2 to the culture medium increased the biosynthetic activity of the cells and the accumulation of GAGs compared to the addition of 25 ng/ml FGF-2, 100 ng/ml IGF-1, 5 ng/ml FGF-2 plus 100 ng/ml IGF-1 after 2 weeks of culture [177]
Porcine collagen type II spongesEDC/NHS crosslinkedCanine chondrocytes	Most of the chondrocytes were around the periphery of the sponges, the cells tend to be elongated along the periphery of the scaffolds and round inside the scaffolds. α-smooth muscle actin is present in the cytoplasm of the cells after 4 weeks of culture [200]
Porcine collagen type II spongesUV crosslinkedCanine chondrocytes	Chondrocytes maintained chondrogenic morphology and displayed less shrinkage, higher biosynthetic activity and more hyaline cartilage-like tissue formation compared to collagen type I scaffolds after 21 days of culture [204]
Porcine collagen type II and GAG spongesUV crosslinkedCanine chondrocytes	After 4 weeks of culture, a range of pore diameter from 25-257 μm did not affect cell-mediated scaffold contraction and α-smooth muscle actin was present in the cytoplasm of the seeded chondrocytes [205]
Porcine collagen type II and GAG sheetsDHT and EDC-NHS crosslinkedCanine chondrocytes	Scaffolds with low cross-link densities (DHT and low EDC/NHS treatment) enhanced cell proliferation, chondrogenic maintenance and collagen type II synthesis and increased the rate of scaffold degradation compared to scaffolds with high cross-link densities (high EDC/NHS treatment) after 2 weeks of culture [206]
Porcine collagen type II sheetsDHT and EDC-NHS crosslinkedCanine chondrocytes	Static compressions of 50% strain decreased the biosynthetic activity of the chondrocytes (the accumulation rate of 3H-proline-labeled protein and 35S-sulfate-labeled PG over a 24 h period). Dynamic compression (3% strain, 0.1 Hz superimposed on 10% strain offset) upregulated protein and PG biosynthesis compared to statically compressed and uncompressed controls after 7 days of culture [207]
Porcine male and female and articular, tracheal and auricular cartilage collagen type II sponges 4-arm polyethylene glycol succinimidyl glutarateHuman ADSCs	Articular cartilage derived sponges exhibited significantly higher resistance to enzymatic degradation and biomechanical properties in comparison to tracheal and auricular cartilage sponges. Articular cartilage sponges induced the highest sulphated GAG synthesis and aggrecan and collagen type II mRNA expression [208]
Chicken collagen type II and chondroitin sulphate spongesEDC-NHS crosslinkedRabbit chondrocytes	Chondrocytes maintained round morphology. The cell proliferation, the accumulation of proteoglycans and collagen type II were enhanced in collagen type II and CS scaffolds compared to pure collagen type II scaffolds after 14 days of cell culture. A cartilaginous-like layer was formed at the periphery of the scaffolds [160]
Chicken collagen type II hydrogelsNo crosslinkerRabbit chondrocytes	The cells in collagen type II scaffolds maintained chondrogenic phenotype and displayed increased PGs synthesis compared to the cells on polystyrene. > 50% of the newly synthesized PGs were recovered from collagen type II scaffolds compared to 13-16% of those recovered from polystyrene [209]
Squid collagen type II coatingNo crosslinkerMurine chondrocytes	Chondrocytes cultured in the conditioned medium from collagen type II treated M1 macrophages mostly maintained round morphology and displayed mild increase in the expression of MMP13, compared with those in the conditioned medium from untreated M1 macrophages [134]
Lesser spotted dogfish, thorn back ray, cuckoo ray and blonde ray collagen type II sponges 4-arm polyethylene glycol succinimidyl glutarateHuman ADSCs	The lesser spotted dogfish sponges induced the highest collagen α1(I), collagen α1(III) (in comparison to thorn back ray and blonde ray), COMP (in comparison to cuckoo ray and blonde ray) and aggrecan (in comparison to cuckoo ray) gene expression, indicative of highest chondrogenic induction potential [131]
Recombinant human collagen type II hydrogelsNo crosslinkerHuman BMSCs	The cells in the scaffolds displayed similar GAGs deposition and similar chondrogenic marker gene expression and upregulated gene expression of metallopeptidases compared to the high-density cell pellet after 84 days of culture [210]
Recombinant human collagen type II hydrogelsNo crosslinkerBovine chondrocytes	Chondrocytes maintained round morphology and the accumulation of GAGs and collagen type II increased after 4 weeks of culture. The gene expression of aggrecan and collagen type II was increased since week 1 [211]
Collagen type II (species is not mentioned) hydrogelsNo crosslinkerRabbit chondrocytes	The dedifferentiated auricular chondrocytes were converted to articular chondrogenic phenotype in a collagen type II coated environment after 14 days of culture. The converted auricular chondrocytes expressed similar histological and biomechanical features as articular chondrocytes in the scaffolds after 28 days of culture [212]