Abstract
Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating “ready-to-use” hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.
Highlights
Despite extensive work focused on promoting in vitro hyaline-like chondrogenesis within a wide range of 3D culture constructs, these platforms are still broadly unable to sufficiently control both structure and 3D cellular interactions, hindering resulting chondrogenic stability and homogeneity in vitro
Mesenchymal stem cells (MSCs) sheets that are directly transplantable in vivo, which should support more rapid hysheet approaches vitro chondrogenically differentiated alineEmerging cartilage cell replacement at defectprepare sites forinfuture in vivo regenerative therapies
Many clinical therapies exist for treating these defects, none achieve lasting, robust regeneration of hyaline cartilage [1,4,43,76]
Summary
MSC cartilage tissue engineering research has increasingly trended toward developing scaffold-free platforms that offer superior in vitro chondrogenic differentiation and optimized control 3D cellular interactions, and support direct, unassisted delivery for robust engraftment with improved surgical versatility. Of these approaches, cell sheet tissue engineering presents a unique scaffold-free platform that retains endogenous 3D cellular interactions and tissue-like organization for promoting stable in vitro hyaline-like chondrogenesis, while preserving intact adhesion molecules along the transplantation surface for direct in vivo transplantation [12,24,25]. The goal of this review is to discuss current and future directions in the development of tissue-engineered
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