Mesh : Pectins / chemistry Hydrogels / chemistry Animals Lidocaine / administration & dosage chemistry Anastomosis, Surgical / methods Rats Molecular Dynamics Simulation Male Microvessels / drug effects

来  源:   DOI:10.1021/acs.biomac.4c00102   PDF(Pubmed)

Abstract:
Microvascular surgery plays a crucial role in reconnecting micrometer-scale vessel ends. Suturing remains the gold standard technique for small vessels; however, suturing the collapsed lumen of microvessels is challenging and time-consuming, with the risk of misplaced sutures leading to failure. Although multiple solutions have been reported, the emphasis has predominantly been on resolving challenges related to arteries rather than veins, and none has proven superior. In this study, we introduce an innovative solution to address these challenges through the development of an injectable lidocaine-loaded pectin hydrogel by using computational and experimental methods. To understand the extent of interactions between the drug and the pectin chain, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations were conducted in the first step of the research. Then, a series of experimental studies were designed to prepare lidocaine-loaded injectable pectin-based hydrogels, and their characterization was performed by using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and rheological analysis. After all the results were evaluated, the drug-loaded pectin-based hydrogel exhibiting self-healing properties was selected as a potential candidate for in vivo studies to determine its performance during operation. In this context, the hydrogel was injected into the divided vessel ends and perivascular area, allowing for direct suturing through the gel matrix. While our hydrogel effectively prevented vasospasm and facilitated micro- and supermicro-vascular anastomoses, it was noted that it did not cause significant changes in late-stage imaging and histopathological analysis up to 6 months. We strongly believe that pectin-based hydrogel potentially enhanced microlevel arterial, lymphatic, and particularly venous anastomoses.
摘要:
微血管手术在重新连接微米级血管末端中起着至关重要的作用。缝合仍然是小型船只的黄金标准技术;然而,缝合塌陷的微血管管腔是具有挑战性和耗时的,有缝线错位导致失败的风险。尽管已经报道了多种解决方案,重点主要是解决与动脉而不是静脉有关的挑战,没有人被证明是优越的。在这项研究中,我们引入了一种创新的解决方案,通过使用计算和实验方法开发可注射的利多卡因负载果胶水凝胶来应对这些挑战。为了了解药物和果胶链之间相互作用的程度,在研究的第一步中进行了分子动力学(MD)模拟和量子力学(QM)计算。然后,设计了一系列实验研究来制备负载利多卡因的可注射果胶基水凝胶,并利用傅里叶变换红外光谱(FT-IR)对其进行表征,扫描电子显微镜(SEM),和流变分析。在评估了所有结果之后,具有自修复特性的基于果胶的载药水凝胶被选为体内研究的潜在候选者,以确定其在手术过程中的性能。在这种情况下,将水凝胶注射到分开的血管末端和血管周围区域,允许通过凝胶基质直接缝合。虽然我们的水凝胶有效地防止血管痉挛和促进微血管和超微血管吻合,值得注意的是,在长达6个月的晚期影像学和组织病理学分析中,它没有引起显著变化.我们坚信,基于果胶的水凝胶可能会增强微水平动脉,淋巴管,尤其是静脉吻合.
公众号