Causing a large diameter blood vessel to sprout branches and a capillary network on demand to create a new angiosome is key to harnessing to potential of regenerative medicine and advancing reconstructive surgery. Currently this can only be achieved by connecting a vein graft to an artery by microsurgery, the arteriovenous loop technique (AVL). The arterial blood pressure in the thin-walled vein is thought to drive remodelling to create branches, however the surgical complexity limits the application of the technique. In this study we demonstrate that unexpectedly, a vessel density of luminal branches in excess of that achieved by the surgical AVL approach can be induced simply by placing a vein in contact with a microporous calcium phosphate. Only osteoinductive biomaterials have been reported previously, this is thought to be the first report of an angio-inductive material. Pilot studies indicated that the material type greatly affected the degree of luminal vascularization.Material contact with the vein is not a requirement for luminal angiogenesis of the vein and together these findings point to a bioinorganic effect, wherein the degradation of the material both releases a stimulatory ionic milieu and creates space for the developing angiosome.
Creating transplantable vascular networks (angiosomes) that are fed and drained by vessels large enough to be surgically reconnected is key to harnessing the potential of regenerative medicine and advancing reconstructive surgical techniques. Currently, the only way to create a new angiosome is nontrivial and involves pressurizing a vein graft by its surgical attachment to an artery forming an arteriovenous loop (AVL). Material induction of a venous angiosome is reported, by placement of a 3D printed microporous monetite scaffold around a vein and its transplantability is further demonstrated. When the transplanted venosome is cut, it bleeds, illustrating potential reconstructive functionality. The volume of blood vessels generated by biomaterial-induction is as great as by AVL. Direct contact of the material with the vein does not appear to be critical to luminal sprouting, and wrapping the implant in a silicone membrane significantly reduces sprouting. Pilot studies with microporous polymeric scaffolds induce far less vascular invasion. After 4 weeks, monetite scaffolds are extensively vascularized and can be transplanted to an arterial vessel. This report is significant since a lack of tools to control vascular generation is an impediment to the treatment of several conditions that give rise to tissue ischemia and tissue reconstruction.
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