Effect of pore size and spacing on neovascularization of a biodegradble shape memory polymer perivascular wrap

Abstract

Neointimal hyperplasia (NH) is a main source of failures in arteriovenous fistulas and vascular grafts. Several studies have demonstrated the promise of perivascular wraps to reduce NH via promotion of adventitial neovascularization and providing mechanical support. Limited clinical success thus far may be due to inappropriate material selection (e.g., nondegradable, too stiff) and geometric design (e.g., pore size and spacing, diameter). The influence of pore size and spacing on implant neovascularization is investigated here for a new biodegradable, thermoresponsive shape memory polymer (SMP) perivascular wrap. Following an initial pilot, 21 mice were each implanted with six scaffolds: four candidate SMP macroporous designs (a–d), a nonporous SMP control (e), and microporous GORETEX (f). Mice were sacrificed after 4 (N = 5), 14 (N = 8), and 28 (N = 8) days. There was a statistically significant increase in neovascularization score between all macroporous groups compared to nonporous SMP (p < .023) and microporous GORETEX (p < .007) controls at Day 28. Wider‐spaced, smaller‐sized pore designs (223 μm‐spaced, 640 μm‐diameter Design c) induced the most robust angiogenic response, with greater microvessel number (p < .0114) and area (p < .0055) than nonporous SMPs and GORETEX at Day 28. This design also produced significantly greater microvessel density than nonporous SMPs (p = 0.0028) and a smaller‐spaced, larger‐sized pore (155 μm‐spaced, 1,180 μm‐sized Design b) design (p = .0013). Strong neovascularization is expected to reduce NH, motivating further investigation of this SMP wrap with controlled pore spacing and size in more advanced arteriovenous models.

Fabrication of Biomedical Scaffolds Using Biodegradable Polymers

“…Light is also frequently used as a stimulus for SMPs . The most prominent examples of biodegradable SMPs are PCL and PLA. ,− As the T g of PCL is below ambient temperature, its T m is targeted as the thermal transition for establishing temporary physical cross-links. A permanent network can be established in PCL through chemical cross-linking to improve shape fixity and shape recovery.…”

Porous biomaterials for tissue engineering: a review

“…For example, PCL has been proposed as a perivascular wrap which is mouldable at body temperature, and allows the scaffold to mimic the patient's venous geometry. 46 In a similar research direction, porous PCL-SMP scaffolds were developed as ''self-fit'' craniomaxillo facial bone 47 and femoral defects. 47,48 Finally, conjugated polymers are polymers with a backbone that alternates single-and double-bonds, which creates delocalized p-electrons which makes them electrically conductive.…”

“…For example, PCL has been proposed as a perivascular wrap which is mouldable at body temperature, and allows the scaffold to mimic the patient's venous geometry. 46 In a similar research direction, porous PCL-SMP scaffolds were developed as “self-fit” cranio-maxillo facial bone 47 and femoral defects. 47,48…”

A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling

“…S4 ). At 4 weeks, the varying degrees of neointima present in the luminal surfaces of the grafts with different pore sizes is likely caused by the different morphology of the graft surface due to the different pore sizes [ 9 ]. During H&E analysis, we observed some dark brown-stained tissue in the grafts with small and medium pore sizes that were not present in the grafts with large pore size.…”

“…In addition to the mechanical dynamics, material features such as the structure and morphology of the scaffolds have received increasing attention for tissue regeneration [ [7] , [8] , [9] , [10] ]. Pore sizes within the implanted material have been accepted as an important factor influencing macrophage polarization, which further regulate tissue regeneration including vascular remodeling [ 11 ].…”