Collagen Scaffolds in Cartilage Tissue Engineering and Relevant Approaches for Future Development

Abstract

BACKGROUND: Cartilage tissue engineering (CTE) aims to obtain a structure mimicking native cartilage tissue through the combination of relevant cells, three-dimensional scaffolds, and extraneous signals. Implantation of 'matured' constructs is thus expected to provide solution for treating large injury of articular cartilage. Type I collagen is widely used as scaffolds for CTE products undergoing clinical trial, owing to its ubiquitous biocompatibility and vast clinical approval. However, the long-term performance of pure type I collagen scaffolds would suffer from its limited chondrogenic capacity and inferior mechanical properties. This paper aims to provide insights necessary for advancing type I collagen scaffolds in the CTE applications. METHODS: Initially, the interactions of type I/II collagen with CTE-relevant cells [i.e., articular chondrocytes (ACs) and mesenchymal stem cells (MSCs)] are discussed. Next, the physical features and chemical composition of the scaffolds crucial to support chondrogenic activities of AC and MSC are highlighted. Attempts to optimize the collagen scaffolds by blending with natural/synthetic polymers are described. Hybrid strategy in which collagen and structural polymers are combined in non-blending manner is detailed. RESULTS: Type I collagen is sufficient to support cellular activities of ACs and MSCs; however it shows limited chondrogenic performance than type II collagen. Nonetheless, type I collagen is the clinically feasible option since type II collagen shows arthritogenic potency. Physical features of scaffolds such as internal structure, pore size, stiffness, etc. are shown to be crucial in influencing the differentiation fate and secreting extracellular matrixes from ACs and MSCs. Collagen can be blended with native or synthetic polymer to improve the mechanical and bioactivities of final composites. However, the versatility of blending strategy is limited due to denaturation of type I collagen at harsh processing condition. Hybrid strategy is successful in maximizing bioactivity of collagen scaffolds and mechanical robustness of structural polymer. CONCLUSION: Considering the previous improvements of physical and compositional properties of collagen scaffolds and recent manufacturing developments of structural polymer, it is concluded that hybrid strategy is a promising approach to advance further collagen-based scaffolds in CTE. Keywords Cartilage tissue engineering Á Type I collagen Á Articular chondrocytes Á Mesenchymal stem cells Á Hybrid scaffolds

Effect of cyclic compression on bone marrow mesenchymal stromal cells in tissue engineered cartilage scaffold

“…Pore size of the top layer was 332.71 ± 52.63 μm. This was consistent with the existing study, which reported that pore sizes larger than 300 μm were advantageous to support the chondrogenic differentiation of rBMSC and their subsequent production of cartilage‐related matrices . Pore size was decreased gradually from the top layer to the bottom.…”

“…This was consistent with the existing study, which reported that pore sizes larger than 300 μm were advantageous to support the chondrogenic differentiation of rBMSC and their subsequent production of cartilage-related matrices. 34 Pore size was decreased gradually from the top layer to the bottom. The contents of CS and SF changed in different layers of the scaffold, mimicking the histological structure of joint cartilage.…”

Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients

“…Previous studies reported that the pivot role, for hASCs osteogenic differentiation, is played by the HA, whereas the collagen mainly supports the survival, proliferation, and chondrogenic differentiation …”

An injectable, click-crosslinked, cytomodulin-modified hyaluronic acid hydrogel for cartilage tissue engineering

“…Cartilage tissue engineering is considered a promising modality for effective repair of damaged cartilage tissue 7,8 . The procedure most often used in cartilage tissue engineering involves a suitable combination of seeded cells, a biocompatible scaffold, and biological factors that support cartilage formation.…”