Employing the Sirolimus-Eluting Poly (Propylene Carbonate) Mesh for the Prevention of Arteriovenous Graft Stenosis in Rats

Abstract

Poly (propylene carbonate, PPC) is a new member of the aliphatic polyester family. An outstanding feature of PPC is that it produces mainly water and carbon dioxide when degraded in vivo, causing minimal side effects. This unique property together with excellent biocompatibility and biodegradability makes PPC a promising material for drug delivery. In this study, we explored the effect of the sirolimus (an inhibitor of cell growth)-eluting PPC mesh on graft stenosis and its possible mechanisms in a rat arteriovenous grafting model. The PPC mesh was prepared by electrospinning. A jugular vein to abdominal aortic autograft transplantation model was established in rats. The graft was then treated by wrapping with the drug mesh or the drug-free mesh or left untreated. Four weeks posttransplantation, neointima was measured with hematoxylin and eosin staining, matrix metalloproteinase-2 (MMP-2), and MMP-9, and proliferating cell nuclear antigen (PCNA) in the grafts were assayed by Western blotting and immunohistochemistry, respectively. In vitro rat aortic adventitial fibroblast cell (RAAFC) migration was assessed using the Boyden chamber assay, and phospho-mammalian target of rapamycin (mTOR) levels in RAAFCs were determined by Western blotting. Animals with the drug mesh had an intimal area index of 4.87% + 0.98%, significantly lower than that of the blank group (14.21% + 2.56%) or the PPC group (15.03% + 2.35%, both P < .05). The sirolimus mesh markedly suppressed MMP-2 and MMP-9 expression, decreased PCNA-positive cell numbers, inhibited RAAFC migration, and reduced phospho-mTOR levels. Our data suggest that the sirolimus-eluting PPC mesh might be potentially applied for the management of grafting stenosis.

A critical review of surgical strategies to minimise venous stenosis in arteriovenous grafts

“…A further novel approach has been proposed to directly modulate the unwanted hypertrophic response with the prophylactic use of externally applied cell-growth inhibitors such as sirolimus. [60][61][62] It is hoped that further randomised trials using such techniques may fulfil the promise of these earlier studies. It may be that prophylactic direct application with a longer acting device such as an applied wrap may have a better outcome than awaiting the development of VS and subsequently then using a similar type of dug therapeutically via a balloon angioplasty.…”

Ternary copolymers from carbon dioxide, cyclohexane dicarboxylic anhydride, and propylene oxide with improved thermal and mechanical properties

“…Copolymerization of CO 2 with epoxides to generate aliphatic polycarbonate is a promising route. Poly(propylene carbonate) (PPC), synthesized by alternating copolymerization of CO 2 and propylene oxide (PO), shows exceptional properties, such as biodegradability, biocompatibility, and gas barrier, 11,12 attracting particular interest in the field of biomedicine, food packaging, and agriculture 12–15 . However, PPC is deficient in low glass transition temperature ( T g ), poor thermal stability, and low mechanical properties (e.g., low Young's modulus and tensile strength), which restrict its wide applications 14–16 …”

“…[12][13][14][15] However, PPC is deficient in low glass transition temperature (T g ), poor thermal stability, and low mechanical properties (e.g., low Young's modulus and tensile strength), which restrict its wide applications. [14][15][16] Four strategies have been developed to improve PPC, (1) terpolymerization to introduce the third monomers through synthesis, [17][18][19][20][21][22][23] (2) crosslinking to form an inter-bonded structure, [24][25][26][27] (3) chain extending 28 or capping 29 of the hydroxyl end groups, and (4) physical blending with nanofillers or other polymers. [30][31][32][33][34] Among them, terpolymerization is convenient and effective for tuning the copolymer structure at the molecular level and improving polymer properties.…”