Zhu Qinchao, Zhou Xuhao, Zhang Yanan, Ye Di, Yu Kang, Cao Wangbei, Zhang Liwen, Zheng Houwei, Sun Ziyang, Guo Chengchen, Hong Xiaoqian, Zhu Yang, Zhang Yajun, Xiao Ying, Valencak Teresa G, Ren Tanchen, Ren Daxi
Institute of Dairy Science, College of Animal Sciences, Zhejiang University, 310058, Hangzhou, China.
Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310027, Hangzhou, China.
Biomater Res. 2023 Feb 3;27(1):6. doi: 10.1186/s40824-023-00346-1.
Post-traumatic massive hemorrhage demands immediately available first-aid supplies with reduced operation time and good surgical compliance. In-situ crosslinking gels that are flexibly adapting to the wound shape have a promising potential, but it is still hard to achieve fast gelation, on-demand adhesion, and wide feasibility at the same time.
A white-light crosslinkable natural milk-derived casein hydrogel bioadhesive is presented for the first time. Benefiting from abundant tyrosine residues, casein hydrogel bioadhesive was synthesized by forming di-tyrosine bonds under white light with a ruthenium-based catalyst. We firstly optimized the concentration of proteins and initiators to achieve faster gelation and higher mechanical strength. Then, we examined the degradation, cytotoxicity, tissue adhesion, hemostasis, and wound healing ability of the casein hydrogels to study their potential to be used as bioadhesives.
Rapid gelation of casein hydrogel is initiated with an outdoor flashlight, a cellphone flashlight, or an endoscopy lamp, which facilitates its usage during first-aid and minimally invasive operations. The rapid gelation enables 3D printing of the casein hydrogel and excellent hemostasis even during liver hemorrhage due to section injury. The covalent binding between casein and tissue enables robust adhesion which can withstand more than 180 mmHg blood pressure. Moreover, the casein-based hydrogel can facilitate post-traumatic wound healing caused by trauma due to its biocompatibility.
Casein-based bioadhesives developed in this study pave a way for broad and practical application in emergency wound management.
创伤后大量出血需要即时可用的急救用品,以缩短操作时间并提高手术顺应性。能够灵活适应伤口形状的原位交联凝胶具有广阔的应用前景,但要同时实现快速凝胶化、按需粘附和广泛的可行性仍很困难。
首次提出一种可通过白光交联的天然乳源酪蛋白水凝胶生物粘合剂。得益于丰富的酪氨酸残基,酪蛋白水凝胶生物粘合剂在白光下使用钌基催化剂通过形成二酪氨酸键合成。我们首先优化了蛋白质和引发剂的浓度,以实现更快的凝胶化和更高的机械强度。然后,我们研究了酪蛋白水凝胶的降解、细胞毒性、组织粘附、止血和伤口愈合能力,以探讨其作为生物粘合剂的应用潜力。
酪蛋白水凝胶可通过户外手电筒、手机手电筒或内窥镜灯引发快速凝胶化,这便于其在急救和微创手术中使用。快速凝胶化使酪蛋白水凝胶能够进行3D打印,甚至在肝切伤出血时也具有出色的止血效果。酪蛋白与组织之间的共价结合实现了牢固的粘附,能够承受超过180 mmHg的血压。此外,基于酪蛋白的水凝胶因其生物相容性,可促进创伤后伤口愈合。
本研究开发的基于酪蛋白的生物粘合剂为在紧急伤口处理中的广泛实际应用铺平了道路。