Effect of chemical immobilization of SDF-1α into muscle-derived scaffolds on angiogenesis and muscle progenitor recruitment

Abstract

The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here, we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix promotes cellular behaviour in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle. SDF-1α, a potent cell homing factor involved in muscle repair, was physically adsorbed or chemically immobilized in these muscle-derived sponges. The immobilized sponges showed significantly higher SDF-1α conjugation efficiency along with improved metabolism and infiltration of muscle-derived stem cells in vitro, and thus generated uniform cellular constructs. In vivo, femoral muscle implantation in rats revealed a negligible immune response in all scaffold groups. We observed enhanced engraftment, neovascularization, and infiltration of CXCR4 cells in the immobilized-SDF-1α sponge compared with nonimmobilized controls. Although Pax7 cells identified adjacent to the immobilized-SDF-1α implantation site, other factors appear to be necessary for efficient penetration of Pax7 cells into the sponge. These findings suggest that immobilization of cell homing factors via chemical mediators can result in recruitment of cells to the microenvironment with subsequent improvement in angiogenesis.

Biomaterials for protein delivery for complex tissue healing responses

“…Review over protein presentation in vivo compared to physical encapsulation. 45,46 Covalent conjugation strategies are valuable in situations where long-term protein presentation is necessary to elicit a sustained cellular response in vivo. Protein immobilization is often achieved using amine-reactive chemistry, which requires an amine group available for nucleophilic attack, or carboxyl-reactive chemistry, which requires a carboxyl group for electrophilic attack.…”

Promoting endogenous repair of skeletal muscle using regenerative biomaterials

“…While the SDF‐1α releasing hydrogel was able to restore blood perfusion, the collagen hydrogel without SDF‐1α showed similar results. SDF‐1α has also been chemically immobilized onto a muscle derived decellularized ECM (dECM) sponge 103 . When implanted into muscle, the sponges with immobilized‐ SDF‐1α increased vessel density and size compared to adsorbed‐ SDF‐1α sponges or blank sponges.…”

Vascularization of 3D Engineered Tissues

“…Moreover, implantation of this sponge scaffold in the rat femoral muscle increased neovascularization, infiltration of host Pax7+, and CXCR4+ cells toward the sponge. (Rajabi et al 2018). Alvarez Fallas et al demonstrated that acellular muscle ECM preserved pro-angiogenic protein, such as HGF, VEGF, and SDF-1α.…”