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

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 (****P < 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.