Muscle acellular scaffold as a biomaterial: effects on C2C12 cell differentiation and interaction with the murine host environment

Abstract

The extracellular matrix (ECM) of decellularized organs possesses the characteristics of the ideal tissue-engineering scaffold (i.e., histocompatibility, porosity, degradability, non-toxicity). We previously observed that the muscle acellular scaffold (MAS) is a pro-myogenic environment in vivo. In order to determine whether MAS, which is basically muscle ECM, behaves as a myogenic environment, regardless of its location, we analyzed MAS interaction with both muscle and non-muscle cells and tissues, to assess the effects of MAS on cell differentiation. Bone morphogenetic protein treatment of C2C12 cells cultured within MAS induced osteogenic differentiation in vitro, thus suggesting that MAS does not irreversibly commit cells to myogenesis. In vivo MAS supported formation of nascent muscle fibers when replacing a muscle (orthotopic position). However, heterotopically grafted MAS did not give rise to muscle fibers when transplanted within the renal capsule. Also, no muscle formation was observed when MAS was transplanted under the xiphoid process, in spite of the abundant presence of cells migrating along the laminin-based MAS structure. Taken together, our results suggest that MAS itself is not sufficient to induce myogenic differentiation. It is likely that the pro-myogenic environment of MAS is not strictly related to the intrinsic properties of the muscle scaffold (e.g., specific muscle ECM proteins). Indeed, it is more likely that myogenic stem cells colonizing MAS recognize a muscle environment that ultimately allows terminal myogenic differentiation. In conclusion, MAS may represent a suitable environment for muscle and non-muscle 3D constructs characterized by a highly organized structure whose relative stability promotes integration with the surrounding tissues. Our work highlights the plasticity of MAS, suggesting that it may be possible to consider MAS for a wider range of tissue engineering applications than the mere replacement of volumetric muscle loss.

Controlling stem cell behavior with decellularized extracellular matrix scaffolds

“…The effects of muscle ECM scaffolds may however not dominate over soluble differentiation cues. Perniconi et al observed that although mouse muscle ECM can provide the necessary cues for differentiation along a muscle lineage, it does not prevent differentiation to other lineages when cells are exposed to specific growth factors [83]. While some of these results are promising, further research is still needed on decellularized skeletal muscle materials for tissue engineering.…”

Innovative approach for the in vitro research on biomedical scaffolds designed and customized with CAD-CAM technology

“…3 Therefore, the comparability between two or more materials is an important prerequisite to clearly define the characteristics of the investigated materials. In recent years, regenerative medicine issues have stimulated research to investigate an elevated number of new biomatrices 4 aimed at improving tissue healing; in this light, the old concept of bioscaffolds has given way to new concepts, such as acellular scaffolds, 5 cell niche, and cell commitment. [6][7][8][9][10] Regarding the scaffolds, the exposed surface area and porosity play major roles in the proliferative response of cultured cells.…”

<b>Avaliação de matrizes descelularizadas para regeneração muscular</b>

“…Existem diversos tipos de biomateriais utilizados na medicina regenerativa, como os biomateriais naturais (biológicos), os quais podem ser derivados de fonte autóloga, alogênica ou xenogênica, e biomateriais sintéticos ou uma mistura dos dois tipos, chamados de biomateriais híbridos . Os biomateriais devem apresentar, como característica, histocompatibilidade, bioatividade, mínima citotoxicidade e ser reabsorvível por processo de biodegradação, restabelecendo o nicho, permitindo a adesão, sobrevivência e diferenciação celular e exercendo influências mecânicas e biológicas no tecido (JONG et al, 2014;PERNICONI et al, 2014).…”