Highly Porous Type II Collagen-Containing Scaffolds for Enhanced Cartilage Repair with Reduced Hypertrophic Cartilage Formation

Abstract

The ability to regenerate damaged cartilage capable of long-term performance in an active joint remains an unmet clinical challenge in regenerative medicine. Biomimetic scaffold biomaterials have shown some potential to direct effective cartilage-like formation and repair, albeit with limited clinical translation. In this context, type II collagen (CII)-containing scaffolds have been recently developed by our research group and have demonstrated significant chondrogenic capacity using murine cells. However, the ability of these CII-containing scaffolds to support improved longer-lasting cartilage repair with reduced calcified cartilage formation still needs to be assessed in order to elucidate their potential therapeutic benefit to patients. To this end, CII-containing scaffolds in presence or absence of hyaluronic acid (HyA) within a type I collagen (CI) network were manufactured and cultured with human mesenchymal stem cells (MSCs) in vitro under chondrogenic conditions for 28 days. Consistent with our previous study in rat cells, the results revealed enhanced cartilage-like formation in the biomimetic scaffolds. In addition, while the variable chondrogenic abilities of human MSCs isolated from different donors were highlighted, protein expression analysis illustrated consistent responses in terms of the deposition of key cartilage extracellular matrix (ECM) components. Specifically, CI/II-HyA scaffolds directed the greatest cell-mediated synthesis and accumulation in the matrices of type II collagen (a principal cartilage ECM component), and reduced deposition of type X collagen (a key protein associated with hypertrophic cartilage formation). Taken together, these results provide further evidence of the capability of these CI/II-HyA scaffolds to direct enhanced and longer-lasting cartilage repair in patients with reduced hypertrophic cartilage formation.