Encapsulation of ePTFE in prevascularized collagen leads to peri‐implant vascularization with reduced inflammation

Abstract

During the typical healing response to an implanted biomaterial, vascular-rich granulation tissue forms around the implant and later resolves into a relatively avascular, fibrous capsule. We have previously shown that a microvascular construct (MVC) consisting of isolated microvessel fragments suspended in a collagen I gel forms a persistent microcirculation in lieu of avascular scar when implanted. The current study evaluated the potential for microvascular constructs to maintain a vascularized tissue environment around an implanted biomaterial. An analysis of the peri-implant tissue around bare expanded polytetrafluoroethylene (ePTFE), ePTFE embedded within a microvascular construct, or ePTFE embedded within collagen alone revealed that the presence of the MVC, but not collagen alone, promoted vascular densities comparable to that of the granulation tissue formed around bare ePTFE. The vessels within the microvascular construct surrounding the ePTFE were perfusion competent, as determined by India ink perfusion casting, and extended into the interstices of the polymer. In contrast to bare ePTFE, the presence of the MVC or collagen alone significantly reduced the number of activated macrophages in association with ePTFE. Similar results were observed for ePTFE modified to increase cellularity and prevent the formation of an avascular scar. The microvascular construct may prove effective in forming vascularized tissue environments and limiting the number of activated macrophages around implanted polymers thereby leading to effective implant incorporation.

Vascularization and cellular isolation potential of a novel electrospun cell delivery vehicle

“…Moreover, the electrospun fibers are not rigid and cells most likely can increase the pore size by physical mechanisms. It is also conceivable that this cell isolation device can be functionalized by covalent localization of proangiogenic factors or enveloped completely in autologous adipose derived microvessels to accelerate the formation of a functional vascular bed prior to injection of cells or islets …”

Determinants of Microvascular Network Topologies in Implanted Neovasculatures

“…We have previously reported that neovasculatures comprised of isolated, intact microvessel segments (arterioles, capillaries, and venules) suspended in collagen type I gels (called a microvascular construct (MVC)) 10 spontaneously undergo sprouting angiogenesis in culture and form functional, hierarchical microvascular networks when implanted 4, 11-13 . In this system, a mature microcirculation forms from neovessels generated via angiogenic sprouting that progress into an immature network and subsequently mature via structural adaptation and network remodeling into a microcirculation 4, 13 .…”

“…We have previously used these MVCs in a number of applications to prevent the progression of ischemic lesions following myocardial infarction 12 to improve biomaterial biocompatibility 11 , to support islet transplantation 14 , and to generate prevascularized tissue constructs 15, 16 . Furthermore, we have developed an in vitro culture system that supports scale up of the MVCs and MVC engineering 17 .…”

Implantable tissue isolation chambers for analyzing tumor dynamics in vivo

“…Furthermore, as opposed to in vitro studies that impose exogenous matrices such as collagen, fibronectin or matrigel, the ECM in our chambers is entirely fabricated by native stromal cells and remodeled by endogenous mechanisms. These early events –vessel sprout infiltration and matrix deposition-- can be initiated by the chamber itself 35, 36 , thus accelerating the process of tumor integration. Similar approaches could be used to encourage vascularization in tissue engineering applications.…”