Poly(L-lactide-co-ɛ-caprolactone)/gelatin-based small-diameter vascular grafts: Salutatory effect of the BVLD and EGCG-Cu to promote hemocompatibility and nitric oxide production for in situ blood vessel regeneration

[Display omitted] •Small-diameter vascular grafts (SDVGs) loaded with Bivalirudin (BVLD) and the epigallocatechin gallate-copper (EGCG-Cu) complex (PG-EB) were prepared via electrospinning, BVLD effectively inhibited thrombosis while EGCG-Cu catalyzed NO generation from endogenous donors, thereby co...

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Veröffentlicht in:Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-11, Vol.500, p.156555, Article 156555
Hauptverfasser: Cai, Guangfang, Yuan, Zhengchao, Wang, Xinyi, Wu, Siyuan, Zhou, Shasha, Lei, Zheng, Li, Peng, EL-Newehy, Mohamed, Moydeen Abdulhameed, Meera, Shafiq, Muhammad, Mo, Xiumei, Jiang, Shichao, Gu, Hongbing
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Sprache:eng
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Zusammenfassung:[Display omitted] •Small-diameter vascular grafts (SDVGs) loaded with Bivalirudin (BVLD) and the epigallocatechin gallate-copper (EGCG-Cu) complex (PG-EB) were prepared via electrospinning, BVLD effectively inhibited thrombosis while EGCG-Cu catalyzed NO generation from endogenous donors, thereby conferring SDVGs with functions similar to those of the natural vascular endothelium layer.•EGCG-Cu is porous, which can effectively load and gradually release BVLD, PG-EBgrafts manifested drug release for up to 40 days in vitro.•PG-EB grafts could effectively inhibit thrombosis, alleviate inflammation, inhibit the proliferation of smooth muscle cells (SMCs), and ultimately regenerating vascular tissues.•PG-EB grafts were successfully transplanted into a rabbit abdominal aorta model and maintained patency without acute thrombosis formation within 1 month. Polymeric small-diameter vascular grafts (SDVGs, inner diameter, < 6 mm) with characteristics, such as thrombo-protection and adequate short-term as well as long-term patency are still in the development and exploration stage. In this study, based on the gas signaling molecule release strategy, SDVGs were prepared by electrospinning using poly(L-lactide-co-ɛ-caprolactone) (PLCL) and gelatin (Gel). Bivalirudin (BVLD) and epigallocatechin gallate-copper (EGCG-Cu) complex were loaded into SDVGs to improve hemocompatibility and nitric oxide (NO) release, respectively. Vascular grafts manifested drug release for up to 40 days in vitro; BVLD effectively inhibited thrombosis while the EGCG-Cu complex catalyzed the NO production from endogenous donors (S-nitroso glutathione (GSNO) and glutathione (GSH)), thereby conferring vascular grafts with functions similar to that of the natural vascular endothelium layer. Both in vitro and in vivo tests demonstrated that SDVGs co-loaded with BVLD and EGCG-Cu (PG-EB) could effectively inhibit thrombosis, alleviate inflammation, and suppress the proliferation of smooth muscle cells (SMCs) while promoting the proliferation of endothelial cells (ECs), and finally regenerate vascular tissues. In vivo animal experiments demonstrated that vascular grafts could promote endothelialization and vascular remodeling. In summary, our simultaneous utilization of BVLD and EGCG-Cu may offer a promising avenue for the fabrication of in situ regenerable SDVGs.
ISSN:1385-8947
DOI:10.1016/j.cej.2024.156555