There are various scaffolds used for cartilage tissue engineering as a 3D environment facilitates to maintain chondrocyte properties than monolayer culture. The characteristics of a scaffold involve mechanical strength, biocompatibility, biodegradability, porosity and toxicity [
36]. The scaffold must be structurally stable, allow cells to infiltrate and growth factors to attach. All these characteristics of scaffolds provide cells with healthy microenvironment, beneficial cell-cell interaction and adequate nutrient exchange
in vitro. Thus, the constructs with cells and ECM mimic the cartilage and are more close to the native cartilage tissue than monolayer cells when implanted in the defects. Of so many scaffolds used, we will focus on clinically used scaffolds and those assist to promote ECM production, especially collagen type II production here.
Collagen is a major component in the cartilage matrix and collagen scaffold has long been used for cartilage repair [
37]. Bilayer type I/III collagen membrane has been clinically used worldwide for ACI and MACI and collagen type II production and regeneration of hyaline-like cartilage were obtained during the observations [
38‐
40]. Collagen type II scaffold was also investigated for cartilage repair and
in vivo study revealed newly formed cartilage structure the same with normal cartilage [
41]. Fibrin glue was often limited to use due to its shrinking feature
in vivo. However, when it combined with polyurethane, this new composite scaffold improved cell survival ability and increased the expression of collagen type II and also aggrecan [
42]. Polyglycolic acid/fibrin (PGA/fibrin) scaffolds used for chondrocyte culture also enhanced the redifferentiation of ovine chondrocytes and the induction of collagen type II and aggrecan after culture. Biomechanical tests further supported this scaffolds for chondrocyte culture with a high tensile strength of 3.6 N/mm2 [
43]. Poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic) acid (PLGA), as materials that have been approved by the US Food and Drug Administration for human clinical uses [
44], have been often used for the research of cartilage tissue engineering. Comparing with PLLA, collagen type II and Arg-Gly-Asp (RGD) peptide modified PLLA/PLGA (50:50), collagen type II modified PLLA/PLGA (50:50) exhibits higher collagen type II expression and shows superiority for chondrogenesis both
in vitro and
in vivo[
45]. Besides, based on type I collagen-PLGA scaffold, improved funnel-like collagen-PLGA hybrid scaffold was shown to be a stronger promoter for cartilage regeneration [
46]. PLGA scaffold with hyaluronic acid incorporated substantially promoted collagen synthesis [
47]. Moreover, as PLGA microspheres have been successfully used to immobilize DNA, siRNA and growth factors [
48,
49]. Sox9 expression plasmid loaded PLGA microspheres have been investigated for chondrogenesis. Human MSCs seeded on Sox9 gene and heparinized TGF-β3 coated dexamethsone loaded PLGA microspheres could drastically increase collagen type II expression by 30 times compared with control [
50]. Therefore, gene incorporation provides a new and promising strategy to optimize the property of scaffolds for tissue engineering.
Comparing with the traditional scaffolds, more and more novel scaffolds have been under investigations, including peptide-modified scaffolds and mobile scaffolds. Mesenchymal stem cells cultured in Arg-Gly-Asp-Ser (RGDS) peptide incorporated PEG-based hydrogels had greater gene expression of collagen type II and produced significantly more GAGs comparing with control [
51]. A newly designed synthetic link N peptide nanofiber was suggested to remarkably promote collagen type II and aggrecan production [
52]. Since cell expansion would lead to contact inhibition and to avoid the dedifferentiation of chondrocytes through passaging, mobile scaffold was also examined for chondrocyte culture. Differently from traditional biomaterial scaffolds, the culture surface area of the high-extension silicone rubber dish could increase by 8 folds with a motorized device [
53]. Thus, adequate cells could be obtained and extracellular matrix was simultaneously maintained, including collagen type II, which would drastically decrease through passaging.
ECM-based scaffold is an emerging approach in the field of cartilage tissue engineering in that it may be relatively easy to retain the natural growth factors in the ECM [
54]. Cartilage-derived and cell-derived ECM scaffolds have been investigated and cartilage-like tissues have been observed [
55‐
57]. However, the quality of formed cartilaginous tissue needs to be evaluated and compared. With improvement of the ECM-based scaffold, it would probably be a promising type of scaffolds for cartilage tissue engineering.