For severe burn injuries, successful medical intervention is accomplished by rapidly and safely providing physical barriers that can cover damaged skin tissues, thereby preventing critical danger of extensive bleeding and infection. Despite availability of a large assortment of wound coverage options, the etiology of wound healing is rather complex leading to significant defects in skin repair. The use of cell-mediated treatment approaches in combination with bioengineered wound coverage constructs may provide the missing tool to improve wound healing outcomes. In this study, we have used an engineered 3D PEGylated fibrin (P-fibrin) gel as a scaffold for adipose derived stem cells (ASCs) delivery into the burn injury model. We were able to confirm the presence of ASCs in the wound site two weeks after the initial injury. Delivery of ASCs-containing gels was associated with improved vascularization of the injured area at early time points accompanied by an increased abundance of mannose receptor expressing cells. Moreover, the application of P-fibrin biomaterial exhibited positive effects on early mononuclear cell recruitment and granulation tissue formation without negatively affecting wound closure kinetics or extent of connective tissue deposition. Collectively, our data support the feasibility of using P-fibrin gels in wound dressing applications requiring controlled delivery of viable cells.
Featured Application: Volume and rate of tissue regeneration may be enhanced with increased scaffold porosity as well as increased numbers of non-cultured bone marrow cells.
Abstract:For clinical treatment of skeletal defects, osteoinductive scaffolds must have the ability to conform to the unique geometry of the injury site without sacrificing biologically favorable properties, including porosity. This investigation seeks to combine the osteoinductive properties of porous hydroxyapatite (HA) scaffolds with the beneficial handling characteristics of granules or putties, while evaluating the effects of mesenchymal stem cell (MSC) concentration on the composite grafts' ability to regenerate bone in vivo. The results demonstrate that porous HA granules regenerate significantly larger volumes of bone compared to non-porous HA. Increased MSC concentrations in autologous bone marrow aspirate (BMA) contributed to greater bone regeneration. This effect was most predominant with non-porous HA. While the extent of bone regeneration using non-porous HA was strongly correlated with MSC concentration of the marrow, porous HA microparticles combined with autologous BMA were successful in faster treatment of critically-sized bone defects and with less dependence on the MSC concentration than non-porous HA.
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