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

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...

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Bibliographic Details
Published in:Journal of biomedical materials research. Part A Vol. 109; no. 3; pp. 272 - 288
Main Authors: Boire, Timothy C., Himmel, Lauren E., Yu, Fang, Guth, Christy M., Dollinger, Bryan R., Werfel, Thomas A., Balikov, Daniel A., Duvall, Craig L.
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2021
Wiley Subscription Services, Inc
Subjects:
Angiogenesis
Animals
Biocompatible Materials - chemistry
Biodegradability
Biodegradation
Blood Vessel Prosthesis
Design
Hemodialysis
hemodialysis access
Hyperplasia
Male
Materials selection
Materials Testing
Mice
Mice, Inbred C57BL
neovascularization
Neovascularization, Physiologic
Polymers
Pore size
pore spacing
Porosity
Shape memory
shape memory polymers
Smart Materials - chemistry
Statistical analysis
Tissue Scaffolds - chemistry
Vascularization
pore spacing
hemodialysis access
shape memory polymers
pore size
neovascularization
ISSN:1549-3296, 1552-4965, 1552-4965
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Summary: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.
Bibliography:Funding information
No benefit of any kind will be received either directly or indirectly by the authors. A medical device startup company that has licensed this shape memory polymer wrap technology from Vanderbilt University, VenoStent, Inc., was cofounded by Dr T. C. B. after the majority of this experimental work and analysis was conducted. VenoStent, Inc. is a very early‐stage, prerevenue R&D startup company years away from market. This has in no way compromised the integrity of this research.
American Heart Association, Grant/Award Number: 15PRE25610014; Foundation for the National Institutes of Health, Grant/Award Number: R01 HL122347; National Cancer Institute, Grant/Award Number: 5P30 CA68485‐19; National Center for Advancing Translational Sciences, Grant/Award Number: ULI TR000445; National Science Foundation, Grant/Award Number: AIR‐TT 1542996; Vanderbilt Mouse Metabolic Phenotyping Center, Grant/Award Number: U24 DK059637‐16
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ISSN:1549-3296
1552-4965
1552-4965
DOI:10.1002/jbm.a.37021