Enhanced wound vascularization using a dsASCs seeded FPEG scaffold

Abstract

The bioengineering of autologous vascular networks is of great importance in wound healing. Adipose-derived stem cells (ASCs) are of interest due to their ability to differentiate toward various cell types, including vascular. We hypothesized that adult human ASCs embedded in a three-dimensional PEG-fibrin (FPEG) gel have the ability to modulate vascularization of a healing wound. Initial in vitro characterization of ASCs isolated from discarded burn skin samples (dsASCs) and embedded in FPEG gels indicated they could express such pericyte/smooth muscle cell markers as α-smooth muscle actin, platelet-derived growth factor receptor-β, NG2 proteoglycan, and angiopoietin-1, suggesting that these cells could potentially be involved in a supportive cell role (i.e., pericyte/mural cell) for blood vessels. Using a rat skin excision model, wounds treated with dsASCs-FPEG gels showed earlier collagen deposition and wound remodeling compared to vehicle FPEG treated wounds. Furthermore, the dsASCs-seeded gels increased the number of vessels in the wound per square millimeter by day 16 (~66.7 vs. ~36.9/mm(2)) in these same studies. dsASCs may support this increase in vascularization through their trophic contribution of vascular endothelial growth factor, as determined by in vitro analysis of mRNA and the protein levels. Immunohistochemistry showed that dsASCs were localized to the surrounding regions of large blood-perfused vessels. Human dsASCs may play a supportive role in the formation of vascular structures in the healing wound through direct mechanisms as well as indirect trophic effects. The merging of autologous grafts or bioengineered composites with the host's vasculature is critical, and the use of autologous dsASCs in these procedures may prove to be therapeutic.

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

“…Cell viability data are further supported by examples in the literature using this encapsulation method. [43][44][45] In addition, while the PEG variant used in these experiments is not biodegradable, the method of PEGylation used only allows for the covalent linking of PEG and fibrinogen, not multiple PEG chains. As the fibrin component of these scaffolds is hydrolyzed and enzymatically degraded, the attached PEG chains are expected to solubilize and clear as well.…”

Development and Characterization of an Engraftable Tissue-Cultured Skin Autograft: Alternative Treatment for Severe Electrical Injuries?

“…Focusing on VEGF, we could show that the VEGF concentration increased during the process of TCSA development. This correlates well to results ob- tained in three-dimensional scaffolds inoculated with adipocyte-derived stem cells [Zamora et al, 2013] or dermal fibroblasts [Pinney et al, 2000]. Angiogenic effects are commonly in vitro investigated using angiogenic assays [Meissner et al, 2011a, b;Wojtowicz et al, 2014] or in vivo transplanting in animals [Hartmann-Fritsch et al, 2013].…”

Human Breast Adipose-Derived Stem Cells Transfected with the Stromal Cell-Derived Factor-1 Receptor CXCR4 Exhibit Enhanced Viability in Human Autologous Free Fat Grafts

“…However, the effect of this exogenous cytokine administration is limited by the number of endothelial cells in the transplant. Thus, an alternative, or adjunct, strategy is to increase the number of endothelial cells in the transplant [15]. …”