The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

Abstract

Cartilage matrix is a particularly promising acellular material for cartilage regeneration given the evidence supporting its chondroinductive character. The ‘raw materials’ of cartilage matrix can serve as building blocks and signals for enhanced tissue regeneration. These matrices can be created by chemical or physical methods: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods when combined with physical methods are particularly effective in fully decellularizing such materials. Critical endpoints include no detectable residual DNA or immunogenic antigens. It is important to first delineate between the sources of the cartilage matrix, i.e., derived from matrix produced by cells in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, i.e., decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell derived matrix (DCCM), and devitalized cell derived matrix (DVCM). Delivery of cartilage matrix may be a straightforward approach without the need for additional cells or growth factors. Without additional biological additives, cartilage matrix may be attractive from a regulatory and commercialization standpoint. Source and delivery method are important considerations for clinical translation. Only one currently marketed cartilage matrix medical device is decellularized, although trends in filed patents suggest additional decellularized products may be available in the future. To choose the most relevant source and processing for cartilage matrix, qualifying testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of raw materials, and immunogenic properties of the product.

Coupling Freshly Isolated CD44+Infrapatellar Fat Pad‐Derived Stromal Cells with a TGF‐β3 Eluting Cartilage ECM‐Derived Scaffold as a Single‐Stage Strategy for Promoting Chondrogenesis

“…Given previous studies which suggest that such cartilage ECM derived materials may be chondro-inductive suggests that only 22 relatively low levels of growth factor may need to be added to these scaffolds to facilitate the development of hyaline cartilage. [8,9,11,32] Cartilage ECM-derived scaffolds were found to support chondrogenesis of culture expanded infrapatellar fat pad derived stem cells in vivo. Cell free scaffolds were infiltrated by host cells, however when compared with stem cell seeded groups a more fibrous or fibrocartilaginous tissue was generated.…”

“…[1,7] Devitalised and decellularized ECM-derived from articular cartilage has been used to produce bioactive scaffolds for cartilage tissue engineering applications. [5,[7][8][9][10]11] These scaffolds have been shown to be chondro-inductive in vitro, [8] although their capacity to promote the development of functional hyaline cartilage is enhanced when additionally stimulated with exogenous growth factors such as transforming growth factor (TGF)-β3. [7,12] We have previously demonstrated that cartilage ECM-4 derived scaffolds can also be used to control the delivery and release of TGF-β3 to stem cells, [7] opening up the potential of using such biomaterials as part of an off-theshelf strategy for joint regeneration.…”

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

“…Recently, it has emerged as a source that is rich in both chondroinductive and chondroconductive potential. 18,20,21,[93][94][95] Current commercially available products utilizing articular cartilage and/ or DCC include Biocartilage Ò (Arthrex), De Novo NT Ò and ET Ò Live Graft (Zimmer), and Chondrofix Ò (Zimmer). However, all of these products use cartilage ECM for the purpose of regenerating only cartilage tissue.…”

Tissue Engineering and Regenerative Medicine Technologies in the Treatment of Articular Cartilage Defects

“…Таким образом, естест-венный матрикс хряща может служить временным каркасом и одновременно быть стимулом для ткане-вой регенерации [43]. Предполагается, что создание композитного скаффолда из децеллюляризирован-ного хряща и биоматериала может повысить биоме-ханическую прочность ткани [44].…”