Injectable polyethylene glycol-fibrinogen hydrogel adjuvant improves survival and differentiation of transplanted mesoangioblasts in acute and chronic skeletal-muscle degeneration

Abstract

BackgroundCell-transplantation therapies have attracted attention as treatments for skeletal-muscle disorders; however, such research has been severely limited by poor cell survival. Tissue engineering offers a potential solution to this problem by providing biomaterial adjuvants that improve survival and engraftment of donor cells.MethodsIn this study, we investigated the use of intra-muscular transplantation of mesoangioblasts (vessel-associated progenitor cells), delivered with an injectable hydrogel biomaterial directly into the tibialis anterior (TA) muscle of acutely injured or dystrophic mice. The hydrogel cell carrier, made from a polyethylene glycol-fibrinogen (PF) matrix, is polymerized in situ together with mesoangioblasts to form a resorbable cellularized implant.ResultsMice treated with PF and mesoangioblasts showed enhanced cell engraftment as a result of increased survival and differentiation compared with the same cell population injected in aqueous saline solution.ConclusionBoth PF and mesoangioblasts are currently undergoing separate clinical trials: their combined use may increase chances of efficacy for localized disorders of skeletal muscle.

Biocompatibility of Pegylated Fibrinogen and Its Effect on Healing of Full-Thickness Skin Defects: A Preliminary Study in Rats

“…There was a tendency for a higher tissue maturity of the PEG-fib hydrogel treated wounds after 14 days in the middle of the defect. This confirms previous results of in vitro studies with PEG-hydrogels [21,42]. Differentiation of newly built tissue is also supported by the fact that a basal membrane [50] was visible in all sections of the PEG-fib hydrogel treated and untreated control wounds at the 14 days' time point.…”

“…This is in accordance with other in-vivo experiments where PEG-fib hydrogel biomaterials with progenitor cells were injected into the tibialis anterior muscle of mice [42]. It was shown that the PEG-fib hydrogels provided immediate protection from host inflammation for the implant progenitor cells.…”

“…The short exposure to long-wave UV light radiation seems not to be cytotoxic to cells as it was already shown in vitro [39] and in vivo [42]. When comparing the untreated and hydrogel-treated wounds, there was no difference in the number of immune cells like FBGCs, macrophages, plasma cells and lymphocytes.…”

“…It was shown that the PEG-fib hydrogels provided immediate protection from host inflammation for the implant progenitor cells. It also enhanced cell proliferation in acutely damaged and dystrophic muscles, leading to functional recovery of myofibers [42].…”

“…In vivo, PEG-fib has been applied in wounded bone [24], heart [40,41] and skeletal muscle [42] but has yet to be tested in a skin wound healing application. Using the PEG-fib as a primary resorbable wound dressing that mimics the provisional fibrin ECM and enables cell ingrowth may be a promising approach.…”