The Effect of Projection Microstereolithographic Fabricated Implant Geometry on Myocutaneous Revascularization

Ross M Clark,Kirsten N Cicotte,Paul G Mcguire,Thomas R Howdieshell,Elizabeth L Hedberg-Dirk

doi:10.4236/ss.2014.512079

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.

Highlights

One of the most potent stimuli for new blood vessel growth or neovascularization is ischemia, which induces capillary growth to restore adequate oxygen delivery to hypoxic tissues [1]
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
Despite extensive work documenting the importance of blood flow in angiogenesis and vessel remodeling, little is known about vascular anastomosis at the cellular and molecular level

Summary

Introduction

One of the most potent stimuli for new blood vessel growth or neovascularization is ischemia, which induces capillary growth to restore adequate oxygen delivery to hypoxic tissues [1]. Functional revascularization is essential for the successful healing of cutaneous wounds and involves: the coordinated expression and activity of angiogenic growth factors, chemokines, extracellular proteinases, and cell surface molecules; the recruitment of circulating inflammatory cells; and the sprouting of new vessels from pre-existing vasculature [2]-[4]. Sprouting requires the activation of quiescent endothelial cells by an angiogenic stimulus. Whereas an autologous split-thickness skin graft with an inherent vasculature purportedly becomes perfused in a matter of days by direct anastomosis or inosculation of pre-existing graft vessels with those of the recipient site, avascular skin and tissue equivalents must become perfused entirely by neovascularization from the recipient wound bed, each process dependent upon tissue contact or engraftment [6]. Recent research suggests that the process of anastomosis is not solely driven by chemotactic or haptotactic mechanisms, but rather represents a contact-based process that requires the exploratory properties of specialized endothelial cells and bridging macrophages [7]

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Conclusion