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Abstract
Because cartilage has limited regenerative capability, a fully efficient advanced therapy medicinal product is needed to treat severe cartilage damage. We evaluated a novel biomaterial obtained by decellularizing sturgeon chondral endoskeleton tissue for use in cartilage tissue engineering. In silico analysis suggested high homology between human and sturgeon collagen proteins, and ultra-performance liquid chromatography confirmed that both types of cartilage consisted mainly of the same amino acids. Decellularized sturgeon cartilage was recellularized with human chondrocytes and four types of human mesenchymal stem cells (MSC) and their suitability for generating a cartilage substitute was assessed ex vivo and in vivo. The results supported the biocompatibility of the novel scaffold, as well as its ability to sustain cell adhesion, proliferation and differentiation. In vivo assays showed that the MSC cells in grafted cartilage disks were biosynthetically active and able to remodel the extracellular matrix of cartilage substitutes, with the production of type II collagen and other relevant components, especially when adipose tissue MSC were used. In addition, these cartilage substitutes triggered a pro-regenerative reaction mediated by CD206-positive M2 macrophages. These preliminary results warrant further research to characterize in greater detail the potential clinical translation of these novel cartilage substitutes.
Highlights
The generation of human tissue-like substitutes by tissue engineering (TE) is based on the combination of human cells with biocompatible biomaterials acting as scaffolds [1,2,3].Ideally, biomaterials used in TE should be biomimetic, i.e., able to mimic the structure and biological properties of the native extracellular matrix (ECM), support cell attachment, and promote tissue regeneration [4]
When specific ECM components were analyzed in Decellularized cartilage disks (DCD), we found that the decelluAfterprocess recellularization, all most showed a single layer of cells on structure
We found that proteoglycan content determined by toluidine blue (TB) and alcian blue (AB) remained constant after recellularization, and the differences compared to DCD and S-CTR were not statistically significant
Summary
The generation of human tissue-like substitutes by tissue engineering (TE) is based on the combination of human cells with biocompatible biomaterials acting as scaffolds [1,2,3].Ideally, biomaterials used in TE should be biomimetic, i.e., able to mimic the structure and biological properties of the native extracellular matrix (ECM), support cell attachment, and promote tissue regeneration [4]. Human cartilage consists of a specialized cell population of chondrocytes immersed within a dense ECM containing abundant collagen fibers and proteoglycans. This structure is commonly damaged due to trauma, age-related degeneration or autoimmune diseases, among other causes, and osteochondral lesions are common clinical problems for orthopedic surgeons worldwide [7]. Most hydrogels used in cartilage TE show rapid degradation, which may hinder their in vivo use [9]. For these reasons, the search for a fully functional biomaterial is currently an active area of research in cartilage TE
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