Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage

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.

Enhancing chondrogenic potential via mesenchymal stem cell sheet multilayering

“…Due to this limited healing ability, articular cartilage defects are common precursors for developing or accelerating onset of osteoarthritis (OA), which is challenging to treat successfully once degeneration has begun [ 3 , 4 ]. As healthy articular cartilage exhibits hyaline structure and characteristics, therapies that immediately replace this hyaline cartilage at the site of chondral defects are increasingly being developed [ 1 , [5] , [6] , [7] ].…”

“…Extensive work has been reported for tailoring 3D scaffold-based and scaffold-free platforms for in vitro MSC chondrogenesis to fabricate transplantable hyaline-like cartilage. However, to date, none have achieved reliable clinical translation, due in part to difficulties in reliably differentiating to phenotypically and functionally desirable hyaline cartilage in vitro or in vivo [ 1 , 6 , 21 ].…”

Current Advances in the Regeneration of Degenerated Articular Cartilage: A Literature Review on Tissue Engineering and Its Recent Clinical Translation

“…Its thickness ranges between 2 to 4 mm; however, it exhibits structural and compositional heterogeneity across four different zones, which are the (i) superficial (tangential), (ii) middle (transitional), (iii) deep, and (iv) calcified zones [14]. The structure of healthy articular cartilage is schematized in Figure 1 [15]. mm; however, it exhibits structural and compositional heterogeneity across four different zones, which are the (i) superficial (tangential), (ii) middle (transitional), (iii) deep, and (iv) calcified zones [14].…”

A Comparison of the Capacity of Mesenchymal Stromal Cells for Cartilage Regeneration Depending on Collagen-Based Injectable Biomimetic Scaffold Type

“…The gold standard in cell therapy of cartilage diseases today is the method of autologous chondrocyte implantation which has some disadvantages [ 2 ]. These include the traumatic biopsy of the healthy area of cartilage, the difficulty of expansion, and the possibility of cell dedifferentiation [ 3 ].…”