Biomaterial‐Induction of a Transplantable Angiosome

Abstract

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.

Development of Neovasculature in Axially Vascularized Calcium Phosphate Cement Scaffolds

“…Since prior work had indicated that polymers could not elicit venous sprouting [ 14 ], here we examined the sprouting capacity of other inorganic materials that are in use clinically or have been proposed as bone graft substitutes. Analysis of the XRD patterns ( Figure 7 A) revealed an amorphous cementitious phase of magnesium phosphate, since only peaks characteristic of unreacted magnesium oxide at 43° and 62° 2θ were apparent.…”

“…IL-1β is responsible for crosstalk between macrophages and smooth muscle cells and augments secretion of VEGF in both cell types [ 33 ]. In further support of the role of inflammatory processes, our laboratory previously observed that wrapping a silicone membrane around the outside of the implant prevented any luminal sprouting [ 14 ]. We tentatively attribute this to the prevention of phagocyte infiltration [ 41 ], since F4/80-positive cells were mainly observed in the outer portion of the scaffold initially ( Figure 5 ).…”

“…Our group recently reported a calcium phosphate-mediated angioinduction [ 14 ], which was a preclinical proof of concept that suggested that microsurgical arterial anastomosis of a large-diameter AVL was unnecessary to induce luminal sprouting of large-diameter vessels [ 14 , 15 ]. We also demonstrated that using this technique to vascularize marrow aspirate improved bone formation capacity over non-vascularized constructs (66+/−6% vs. 30+/−4%) [ 15 ].…”