Abstract
Extracellular matrix (ECM)-based materials are attractive for regenerative medicine in their ability to potentially aid in stem cell recruitment, infiltration, and differentiation without added biological factors. In musculoskeletal tissue engineering, demineralized bone matrix is widely used, but recently cartilage matrix has been attracting attention as a potentially chondroinductive material. The aim of this study was thus to establish a chemical decellularization method for use with articular cartilage to quantify removal of cells and analyze the cartilage biochemical content at various stages during the decellularization process, which included a physically devitalization step. To study the cellular response to the cartilage matrix, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured in cell pellets containing cells only (control), chondrogenic differentiation medium (TGF-β), chemically decellularized cartilage particles (DCC), or physically devitalized cartilage particles (DVC). The chemical decellularization process removed the vast majority of DNA and about half of the glycosaminoglycans (GAG) within the matrix, but had no significant effect on the amount of hydroxyproline. Most notably, the DCC group significantly outperformed TGF-β in chondroinduction of rBMSCs, with collagen II gene expression an order of magnitude or more higher. While DVC did not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater down regulation of collagen I, collagen X and Runx2. A new protocol has been introduced for cartilage devitalization and decellularization in the current study, with evidence of chondroinductivity. Such bioactivity along with providing the ‘raw material’ building blocks of regenerating cartilage may suggest a promising role for DCC in biomaterials that rely on recruiting endogenous cell recruitment and differentiation for cartilage regeneration.
Highlights
Degeneration of articular cartilage can be caused by traumatic injury or arthritis
Synthetic biomaterials have achieved clinically relevant mechanical performance for osteochondral implantation; they have not been successful at fully regenerating functional articular cartilage
Cartilage extracellular matrix (ECM) has been used as a scaffolding material that has only been physically devitalized as opposed to being decellularized
Summary
Degeneration of articular cartilage can be caused by traumatic injury or arthritis. Articular cartilage regeneration is a difficult problem because cartilage has a limited capacity for self-repair and low vascularity [1, 2]. Current clinical treatments for cartilage degeneration include autologous chondrocyte implantation (ACI), mosaicplasty, microfracture, and allograft implants. These treatments have limited success in fully regenerating functional articular cartilage. Tissue engineering has aimed to regenerate articular cartilage utilizing synthetic biomaterials due to the ability to alter and control synthetic materials’ mechanical properties [3,4,5]. These synthetic materials, have limited ability to recruit and differentiate stem cells without added biological components such as peptide sequences or growth factors. ECM materials can induce differentiation and regeneration without additional biologic additives, which may be an attractive alternative from both cost and regulatory standpoints [9]
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