Development of a biological scaffold engineered using the extracellular matrix secreted by skeletal muscle cells

Abstract

The performance of implantable biomaterials derived from decellularized tissue, including encouraging results with skeletal muscle, suggests that the extracellular matrix (ECM) derived from native tissue has promising regenerative potential. Yet, the supply of biomaterials derived from donated tissue will always be limited, which is why the in-vitro fabrication of ECM biomaterials that mimic the properties of tissue is an attractive alternative. Towards this end, our group has utilized a novel method to collect the ECM that skeletal muscle myoblasts secrete and form it into implantable scaffolds. The cell derived ECM contained several matrix constituents, including collagen and fibronectin that were also identified within skeletal muscle samples. The ECM was organized into a porous network that could be formed with the elongated and aligned architecture observed within muscle samples. The ECM material supported the attachment and in-vitro proliferation of cells, suggesting effectiveness for cell transplantation, and was well tolerated by the host when examined in-vivo. The results suggest that the ECM collection approach can be used to produce biomaterials with compositions and structures that are similar to muscle samples, and while the physical properties may not yet match muscle values, the in-vitro and in-vivo results indicate it may be a suitable first generation alternative to tissue derived biomaterials.

Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries

“…Using this approach, a polyurethane (PU) foam is generated from a hardened sugar template, and the ECM is synthesized from rat myoblasts [162]. While the PU foam was coated with fibronectin to facilitate myoblast attachment, type I collagen was detected via immunostaining; and laminin and type IV collagen were detected via tandem mass spectroscopy after 4 weeks of culture.…”

The characterization of decellularized human skeletal muscle as a blueprint for mimetic scaffolds

“…Skeletal muscle samples were decellularized using a published [19] SDS-based decellularization protocol [19] familiar to our group and previously used to prepare rat DSM samples [12, 20]. The resulting ECM biomaterial was thoroughly characterized to determine several key physical and chemical properties.…”

“…Guided by this principle, the development of readily available “off the shelf” biomaterials with properties that mimic DSM are an attractive adjunct to tissue derived DSM scaffolds. Research groups [9–11], including ours [12] have reported the development of engineered scaffolds with muscle inspired properties.…”

Whole-organ engineering with natural extracellular materials

“…These smart materials preferably contain ECM molecules as well. To address this problem, Shiloh et al developed a method to collect ECM secreted by skeletal muscle myoblasts, and form it into implantable smart scaffolds [65]. In this study, rat skeletal myoblasts were seeded onto foams that served as a scaffold.…”