Department of Chemical Engineering, Feng Chia University, Taichung, Taiwan.
Taiwan Instrument Research Institute, National Applied Research Laboratories, Hsinchu, Taiwan.
Int J Biol Macromol. 2021 Aug 31;185:441-450. doi: 10.1016/j.ijbiomac.2021.06.162. Epub 2021 Jun 29.
Biomaterials for effective hemorrhage control are urgently needed in clinics as uncontrolled bleeding is associated with high mortality. Herein, we developed an injectable and in situ photo-crosslinkable hybrid hemostatic hydrogel by combining pectin methacrylate (PECMA) and gelatin methacryloyl (GelMA). This modular material system combines ionic- and photo-crosslinking chemistries to design interpenetrating networks (IPN) exhibiting tunable rheology, highly porous structure, and controllable swelling and mechanical properties. By simply changing the calcium (0-15 mM) and polymer (1.5-7%) content used for the sequential crosslinking of hydrogels via calcium gelation and UV-photopolymerization, it was possible to precisely modulate the injectability, degradation, and swelling ratio. Moreover, it is demonstrated that PECMA/GelMA hydrogels present good cytocompatibility and uniquely synergize the hemostatic properties of calcium ions on PECMA, the amine residues on GelMA, and the highly porous network toward rapid blood absorption and fast coagulation effect. An in vitro porcine skin bleeding model confirmed that the hydrogel could be directly injected into the wound and rapidly photo-crosslinked, circumventing the bleeding and decreasing the coagulation time by 39%. Importantly, the crosslinked hydrogel could be easily removed to prevent secondary wound injury. Overall, this injectable hybrid PECMA/GelMA hydrogel stands as a promising hemostatic material.
临床上急需有效的止血生物材料,因为无法控制的出血与高死亡率有关。在此,我们通过将甲基丙烯酸酯化果胶(PECMA)和甲基丙烯酰化明胶(GelMA)相结合,开发了一种可注射和原位光交联的混合止血水凝胶。该模块化材料系统结合了离子交联和光交联化学,设计了具有可调流变学、高度多孔结构以及可控溶胀和机械性能的互穿网络(IPN)。通过简单地改变用于通过钙离子凝胶化和 UV 光聚合对水凝胶进行顺序交联的钙离子(0-15mM)和聚合物(1.5-7%)含量,可以精确调节可注射性、降解性和溶胀比。此外,研究表明,PECMA/GelMA 水凝胶具有良好的细胞相容性,并且独特地协同了 PECMA 上的钙离子、GelMA 上的胺基残留物以及高度多孔网络对快速吸收血液和快速凝血效果的止血性能。体外猪皮出血模型证实,该水凝胶可直接注射到伤口中并迅速光交联,避免出血并将凝血时间缩短 39%。重要的是,交联水凝胶可以轻松去除以防止二次伤口损伤。总体而言,这种可注射的混合 PECMA/GelMA 水凝胶是一种很有前途的止血材料。