仿生非免疫多功能密封剂,用于高效止血和无缝合伤口闭合。

Bioinspired Non-Immunogenic Multifunctional Sealant for Efficient Blood Clotting and Suture-Free Wound Closure.

机构信息

Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India.

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India.

出版信息

ACS Biomater Sci Eng. 2020 Nov 9;6(11):6378-6393. doi: 10.1021/acsbiomaterials.0c01254. Epub 2020 Oct 9.

Abstract

Engineering bioinspired peptide-based molecular medicine is an emerging paradigm for the management of traumatic coagulopathies and inherent bleeding disorder. A hemostat-based strategy in managing uncontrolled bleeding is limited due to the lack of adequate efficacy and clinical noncompliance. In this study, we report an engineered adhesive peptide-based hybrid regenerative medicine, sealant 5, which is designed integrating the structural and functional features of fibrin and mussel foot-pad protein. AFM studies have revealed that sealant 5 (55.8 ± 6.8 nN adhesive force) has higher adhesive force than fibrin (46.4 ± 7.3 nN adhesive force). SEM data confirms that sealant 5 retains its network-like morphology both at 37 and 60 °C, inferring its thermal stability. Both sealant 5 and fibrin exhibit biodegradability in the presence of trypsin, and sealant 5 also showed biocompatibility in the presence of fibroblast cells. Engineered sealant 5 efficiently promotes hemostasis with enhanced adhesiveness and less blood-loss than fibrin. data suggests that in heparinized conditions, sealant 5 ceases bleeding at 212.3 ± 15.1 s, whereas fibrin halts bleeding at 294.3 ± 21.4 s and blood-loss is ∼4-fold less in sealant 5 than in fibrin. In a heparinized system, sealant 5 facilitates faster blood-clotting than fibrin (∼82 s faster) and RADA-16, a reported peptide-based sealant (∼113 s faster). Additionally, in the case of sealant 5, the process of clotting mimicry-like fibrin is independent of the body's own coagulation system. Sealant 5 efficiently halts bleeding for both external and internal wounds, even for a heparinized system overcoming the bacterial infection. ELISA data and PMBC cell proliferation data support the non-immunogenic feature of sealant 5. Though fibrin and sealant 5 have exhibited comparable efficacy in suture-free wound closure, H&E staining images have revealed infiltration of very few immune cells as well as the presence of abundant collagen formation in the case of sealant 5-treated wound. Such nature-inspired non-immunogenic sealants offer exciting possibilities for the treatment of uncontrolled bleeding vis-à-vis wound closure.

摘要

工程仿生肽基分子医学是一种新兴的范式,可用于治疗创伤性凝血病和固有出血性疾病。由于缺乏足够的疗效和临床顺应性,基于止血剂的控制出血策略受到限制。在这项研究中,我们报告了一种基于工程化黏附肽的混合再生医学密封剂 5,它是通过整合纤维蛋白和贻贝足垫蛋白的结构和功能特性设计的。原子力显微镜研究表明,密封剂 5(55.8 ± 6.8 nN 黏附力)的黏附力高于纤维蛋白(46.4 ± 7.3 nN 黏附力)。SEM 数据证实,密封剂 5 在 37 和 60°C 下都保持其网络状形态,这表明其热稳定性。在存在胰蛋白酶的情况下,密封剂 5 和纤维蛋白都表现出可生物降解性,而密封剂 5 在存在成纤维细胞的情况下也表现出生物相容性。工程化的密封剂 5 通过增强的黏附力和较少的失血量来有效地促进止血,其效果优于纤维蛋白。数据表明,在肝素化条件下,密封剂 5 在 212.3 ± 15.1 s 内停止出血,而纤维蛋白在 294.3 ± 21.4 s 内停止出血,并且在肝素化系统中,密封剂 5 的失血量比纤维蛋白少 4 倍。在肝素化系统中,密封剂 5 比纤维蛋白(快约 82 s)和报道的基于肽的密封剂 RADA-16(快约 113 s)更快地促进血液凝结。此外,在密封剂 5 的情况下,类似于纤维蛋白的凝结模拟过程独立于身体自身的凝血系统。密封剂 5 可有效止血,无论是外部还是内部伤口,甚至可以克服细菌感染,用于肝素化系统。ELISA 数据和 PMBC 细胞增殖数据支持密封剂 5 的非免疫原性特征。尽管纤维蛋白和密封剂 5 在无缝线伤口闭合方面表现出相当的疗效,但 H&E 染色图像显示,在密封剂 5 处理的伤口中,只有很少的免疫细胞浸润,并且存在大量的胶原形成。这种受自然启发的非免疫原性密封剂为控制出血和伤口闭合提供了令人兴奋的可能性。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索