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用于增强止血、抗菌和生物可降解益处的仿生去端肽胶原蛋白微纤维的自下而上重构设计。

Bottom-up reconstitution design of a biomimetic atelocollagen microfibril for enhancing hemostatic, antibacterial, and biodegradable benefits.

作者信息

Zhang Xiaoxia, Cai Lin, Li Guoying

机构信息

Key Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, P. R. China.

National Engineering Research Center of Clean Technology in Leather Industry, Sichuan University, Chengdu 610065, P. R. China.

出版信息

J Mater Chem B. 2025 Feb 5;13(6):2074-2090. doi: 10.1039/d4tb02430c.

DOI:10.1039/d4tb02430c
PMID:39760512
Abstract

Powdered collagen is emerging as a promising topical hemostat owing to its adaptability to various wounds, active hemostatic abilities, and biosafety. The reproduction of a bionic structure similar to natural collagen is crucial for effective hemostasis and bioactivity. Additional factors relevant to clinical application include antimicrobial properties, minimal immune response, and straightforward preparation. However, current developments in collagen hemostatic powders often lack comprehensive integration of these multidimensional attributes. In this study, atelocollagen molecules and antimicrobial peptide (ε-polylysine) were successfully employed to achieve the simultaneous expression of biomimetic structures and antimicrobial functions through a bottom-up reconstruction design. The synergistic effects of low temperature and mechanical processing facilitated the dispersion of collagen fibrils without leading to a stiffened network. The resultant atelocollagen microfibril (BCF-10) exhibited biomimetic D-periodicity and a fluffy morphology. BCF-10 demonstrated excellent antimicrobial properties and biocompatibility. Notably, BCF-10 could absorb blood up to 12 times its own weight within 15 s and significantly activate platelets to promote coagulation. In both a rat tail amputation model and a liver multi-point puncture model, BCF-10 exhibited significantly improved hemostatic capability compared to commercially available gauze (**** < 0.0001) and was found to be comparable to the well-established microfibrillar collagen hemostat, Avitene. Immune response assessments indicated that BCF-10 could be biodegraded within 30 days without eliciting a severe inflammatory response, and could serve as a scaffold for cellular infiltration to promote tissue regeneration. This research presents a straightforward and effective strategy for preparing a biomimetic atelocollagen microfibril that is efficient in hemostasis, infection prevention, and rapid biodegradability, positioning BCF-10 as a promising candidate for clinical translation and application.

摘要

由于可适应各种伤口、具有有效的止血能力和生物安全性,胶原粉正成为一种很有前景的局部止血剂。复制与天然胶原相似的仿生结构对于有效的止血和生物活性至关重要。与临床应用相关的其他因素包括抗菌特性、最小的免疫反应和简单的制备方法。然而,目前胶原止血粉的发展往往缺乏对这些多维度属性的全面整合。在本研究中,通过自下而上的重构设计,成功地利用了去端肽胶原分子和抗菌肽(ε-聚赖氨酸)来实现仿生结构和抗菌功能的同时表达。低温和机械加工的协同作用促进了胶原纤维的分散,而不会导致网络变硬。所得的去端肽胶原微纤维(BCF-10)呈现出仿生的D周期和蓬松的形态。BCF-10表现出优异的抗菌性能和生物相容性。值得注意的是,BCF-10在15秒内可吸收高达自身重量12倍的血液,并能显著激活血小板以促进凝血。在大鼠尾部截肢模型和肝脏多点穿刺模型中,与市售纱布相比,BCF-10的止血能力显著提高(****<0.0001),并且发现其与成熟的微纤维胶原止血剂Avitene相当。免疫反应评估表明,BCF-10可在30天内被生物降解,而不会引发严重的炎症反应,并且可作为细胞浸润的支架以促进组织再生。本研究提出了一种简单有效的策略,用于制备一种在止血、预防感染和快速生物降解方面有效的仿生去端肽胶原微纤维,将BCF-10定位为临床转化和应用的有希望的候选者。

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