Li Yinghao, Xiao Dongling, Yan Weixi, Jiang Meilin, Tan Ju, Qin Zhongliang, Zhou Jingting, Sun Yue, Yang Mingcan, Yang Guanyuan, Gu Yawei, Liu Yong, Zhu Chuhong
Department of Anatomy, Engineering Research Center for Organ Intelligent Biological Manufacturing of Chongqing, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, 400038, China.
Engineering Research Center of Tissue and Organ Regeneration and Manufacturing, Ministry of Education, Chongqing, 400038, China.
Bioact Mater. 2024 Nov 16;45:88-101. doi: 10.1016/j.bioactmat.2024.11.003. eCollection 2025 Mar.
Timely and stable sealing of uncontrolled high-pressure hemorrhage in emergency situations outside surgical units remains a major clinical challenge, contributing to the high mortality rate associated with trauma. The currently widely used hemostatic bioadhesives are ineffective for hemorrhage from major arteries and the heart due to the absence of biologically compatible flexible structures capable of simultaneously ensuring conformal tough adhesion and biomechanical support. Here, inspired by the principle of chromatin assembly, we present a tissue-conformable tough matrix for robust sealing of severe bleeding. This hierarchical matrix is fabricated through a phase separation process, which involves the in-situ formation of nanoporous aggregates within a microporous double-network (DN) matrix. The dispersed aggregates disrupt the rigid physical crosslinking of the original DN matrix and function as a dissipative component, enabling the aggregate-based DN (aggDN) matrix to efficiently dissipate energy during stress and achieve improved conformal attachment to soft tissues. Subsequently, pre-activated bridging polymers facilitate rapid interfacial bonding between the matrix and tissue surfaces. They synergistically withstand considerable hydraulic pressure of approximately 700 mmHg and demonstrate exceptional tissue adhesion and sealing in rat cardiac and canine aortic hemorrhages, outperforming the commercially available bioadhesives. Our findings present a promising biomimetic strategy for engineering biomechanically compatible and tough adhesive hydrogels, facilitating prompt and effective treatment of hemorrhagic wounds.
在外科手术单元以外的紧急情况下,及时、稳定地封闭失控的高压出血仍是一项重大临床挑战,这也是导致创伤相关高死亡率的原因之一。目前广泛使用的止血生物粘合剂对于大动脉和心脏出血无效,因为缺乏能够同时确保贴合性强的牢固粘附和生物力学支持的生物相容性柔性结构。在此,受染色质组装原理的启发,我们提出了一种用于强力封闭严重出血的组织贴合性坚韧基质。这种分级基质是通过相分离过程制备的,该过程涉及在微孔双网络(DN)基质中原位形成纳米多孔聚集体。分散的聚集体破坏了原始DN基质的刚性物理交联,并作为耗散成分发挥作用,使基于聚集体的DN(aggDN)基质在受力时能够有效耗散能量,并改善与软组织的贴合性附着。随后,预激活的桥连聚合物促进了基质与组织表面之间的快速界面结合。它们协同承受约700 mmHg的相当大的液压,并在大鼠心脏和犬主动脉出血中表现出出色的组织粘附和封闭性能,优于市售生物粘合剂。我们的研究结果为设计生物力学兼容且坚韧的粘性水凝胶提出了一种有前景的仿生策略,有助于对出血性伤口进行及时有效的治疗。