Skeletal muscle derived stem cells microintegrated into a biodegradable elastomer for reconstruction of the abdominal wall.

Abstract

A variety of techniques have been applied to generate tissue engineered constructs, where cells are combined with degradable scaffolds followed by a period of invitro culture or direct implantation. In the current study, a cellularized scaffold was generated by concurrent deposition of electrospun biodegradable elastomer (poly(ester urethane)urea, PEUU) and electrosprayed culture medium+skeletal muscle-derived stem cells (MDSCs) or electrosprayed culture medium alone as a control. MDSCs were obtained from green fluorescent protein (GFP) transgenic rats. The created scaffolds were implanted into allogenic strain-matched rats to replace a full thickness abdominal wall defect. Both control and MDSC-integrated scaffolds showed extensive cellular infiltration at 4 and 8wk. The number of blood vessels was higher, the area of residual scaffold was lower, number of multinucleated giant cells was lower and area of connective tissue was lower in MDSC-integrated scaffolds (p<0.05). GFP+cells co-stained positive for VEGF. Bi-axial mechanical properties of the MDSC-microintegrated constructs better approximated the anisotropic behavior of the native abdominal wall. GFP+cells were observed throughout the scaffold at ∼5% of the cell population at 4 and 8wk. RNA expression at 4wk showed higher expression of early myogenic marker Pax7, and b-FGF in the MDSC group. Also, higher expression of myogenin and VEGF were seen in the MDSC group at both 4 and 8wk time points. The paracrine effect of donor cells on host cells likely contributed to the differences found invivo between the groups. This approach for the rapid creation of highly-cellularized constructs with soft tissue like mechanics offers an attractive methodology to impart cell-derived bioactivity into scaffolds providing mechanical support during the healing process and might find application in a variety of settings.