Abstract

Understanding cell behavior inside three-dimensional (3D) microenvironments with controlled spatial patterning of physical and biochemical factors could provide insight into the basic biology of tissue engraftment, vascular anastomosis, and revascularization. A simple layer by layer projection microstereolithography (PμSL) method was utilized to investigate the effects of a nonporous and porous bioinert barrier on myocutaneous flap engraftment and revascularization. A cranial-based, peninsular-shaped myocutaneous flap was surgically created on the dorsum of C57Bl6 mice. Porous (SP) and nonporous (S) silicone implants were tailored to precise flap dimensions and inserted between the flap and recipient bed prior to sutured wound closure. Porous implant myocutaneous flaps became engrafted to the recipient site with complete viability. In contrast, distal cutaneous necrosis and resultant flap dehiscence was evident by day 10 in nonporous implant flap mice. Laser speckle contrast imaging demonstrated flap revascularization in (SP) mice, and markedly reduced distal flap reperfusion in (S) mice. Histologic analysis of day 10 (SP) flaps revealed granulation tissue rich in blood vessels and macrophages growing through the implant pores and robust neovascularization of the distal flap. In contrast, the nonporous implant prevented tissue communication between recipient bed and flap with lack of bridging inflammatory cells and neovasculature and resultant distal tissue necrosis. We have fabricated porous and nonporous silicone implants via a simple and inexpensive technique of PμSL. Using a graded-ischemia wound healing model, we have shown that porous implants allowed contact between flap and recipient bed resulting in proximal flap arteriogenesis and neovascularization of the distal flap. Future research will utilize variations in implant pore size, spacing, and location to gain a better understanding of the cellular and molecular mechanisms responsible for myocutaneous flap engraftment, vascular anastomosis, and revascularization.

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