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Oversized Biodegradable Arterial Grafts Promote Enhanced Neointimal Tissue Formation.

ABSTRACT: Most tissue-engineered arterial grafts are complicated by aneurysmal dilation secondary to insufficient neotissue formation after scaffold degradation. The optimal graft would form an organized multilayered structure with a robust extracellular matrix that could withstand arterial pressure. The purpose of the current study was to determine how oversizing a biodegradable arterial scaffold affects long-term neotissue formation. Size-matched (1.0?mm, n?=?11) and oversized (1.6?mm, n?=?9) electrospun polycaprolactone/chitosan scaffolds were implanted as abdominal aortic interposition grafts in Lewis rats. The mean lumen diameter of the 1.6?mm grafts was initially greater compared with the native vessel, but matched the native aorta by 6 months. In contrast, the 1.0?mm grafts experienced stenosis at 6 and 9 months. Total neotissue area and calponin-positive neotissue area were significantly greater in the 1.6?mm grafts by 6 months and similar to the native aorta. Late-term biomechanical testing was dominated by remaining polymer, but graft oversizing did not adversely affect the biomechanics of the adjacent vessel. Oversizing tissue-engineered arterial grafts may represent a strategy to increase the formation of organized neotissue without thrombosis or adverse remodeling of the adjacent native vessel by harnessing a previously undescribed process of adaptive vascular remodeling.

SUBMITTER: Best C

PROVIDER: S-EPMC6079650 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Oversized Biodegradable Arterial Grafts Promote Enhanced Neointimal Tissue Formation.

Best Cameron C Fukunishi Takuma T Drews Joseph J Khosravi Ramak R Hor Kan K Mahler Nathan N Yi Tai T Humphrey Jay D JD Johnson Jed J Breuer Christopher K CK Hibino Narutoshi N

Tissue engineering. Part A 20180510 15-16

Most tissue-engineered arterial grafts are complicated by aneurysmal dilation secondary to insufficient neotissue formation after scaffold degradation. The optimal graft would form an organized multilayered structure with a robust extracellular matrix that could withstand arterial pressure. The purpose of the current study was to determine how oversizing a biodegradable arterial scaffold affects long-term neotissue formation. Size-matched (1.0 mm, n = 11) and oversized (1.6 mm, n = 9) electrospu ...[more]

PMID: 29431029

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Project description:BackgroundThe microbiome has a functional role in a number of inflammatory processes and disease states. While neointimal hyperplasia development has been linked to inflammation, a direct role of the microbiota in neointimal hyperplasia has not yet been established. Germ-free (GF) mice are an invaluable model for studying causative links between commensal organisms and the host. We hypothesized that GF mice would exhibit altered neointimal hyperplasia following carotid ligation compared to conventionally raised (CONV-R) mice.MethodsTwenty-week-old male C57BL/6 GF mice underwent left carotid ligation under sterile conditions. Maintenance of sterility was assessed by cultivation and 16S rRNA qPCR of stool. Neointimal hyperplasia was assessed by morphometric and histologic analysis of arterial sections after 28 days. Local arterial cell proliferation and inflammation was assessed by immunofluorescence for Ki67 and inflammatory cell markers at five days. Systemic inflammation was assessed by multiplex immunoassays of serum. CONV-R mice treated in the same manner served as the control cohort. GF and CONV-R mice were compared using standard statistical methods.ResultsAll GF mice remained sterile during the entire study period. Twenty-eight days after carotid ligation, CONV-R mice had significantly more neointimal hyperplasia development compared to GF mice, as assessed by intima area, media area, intima+media area, and intima area/(intima+media) area. The collagen content of the neointimal lesions appeared qualitatively similar on Masson's trichrome staining. There was significantly reduced Ki67 immunoreactivity in the media and adventitia of GF carotid arteries 5 days after ligation. GF mice also had increased arterial infiltration of anti-inflammatory M2 macrophages compared to CONV-R mouse arteries and a reduced proportion of mature neutrophils. GF mice had significantly reduced serum IFN-?-inducible protein (IP)-10 and MIP-2 5 days after carotid ligation, suggesting a reduced systemic inflammatory response.ConclusionsGF mice have attenuated neointimal hyperplasia development compared to CONV-R mice, which is likely related to altered kinetics of wound healing and acute inflammation. Recognizing the role of commensals in the regulation of arterial remodeling will provide a deeper understanding of the pathophysiology of restenosis and support strategies to treat or reduce restenosis risk by manipulating microbiota.

Dataset Information

Oversized Biodegradable Arterial Grafts Promote Enhanced Neointimal Tissue Formation.

Publications

Oversized Biodegradable Arterial Grafts Promote Enhanced Neointimal Tissue Formation.

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