Biomaterials field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan; Graduate School of Science and Technology, Degree Programs in Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
Biomaterials field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Biomater Adv. 2025 Jan;166:214028. doi: 10.1016/j.bioadv.2024.214028. Epub 2024 Sep 3.
Uncontrollable hemorrhage from trauma and open surgery leads to a high percentage of death. Even though some patch-type hemostatic materials have been used in the clinic, sufficient tissue adhesion property and the management of tissue adhesion and anti-adhesion have been the challenges. In this report, we designed Janus tissue adhesive hemostatic patch, consisting of Alaska pollock gelatin (Org-ApGltn) as a support layer and decanoyl group-modified ApGltn (C10-ApGltn) with pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG) as an adhesive layer, named as the C10-ApGltn patch. The C10-ApGltn patch adhered onto blood vessel surface by the activation 4S-PEG and hydrophobic groups in C10-ApGltn through the covalent bond formation and physical interaction. The burst strength of the C10-ApGltn patch was optimized in terms of the degree of substitution, the molecular weight of 4S-PEG, the concentration of C10-ApGltn, and the NHS/NH ratio. The optimized C10-ApGltn patch showed significantly higher burst strength with commercially available TachoSil®. The C10-ApGltn patch showed enzymatic degradability in a buffer solution with collagenase. In a rat liver hemorrhage model, the C10-ApGltn patch acted as a sealant on the hemorrhage site and exhibited competitive hemostatic property to TachoSil®.
创伤和开放性手术引起的无法控制的出血导致高死亡率。尽管一些贴剂型止血材料已在临床上使用,但足够的组织黏附性能以及组织黏附和抗黏附的管理一直是挑战。在本报告中,我们设计了一种Janus 组织胶止血贴,由阿拉斯加鳕鱼明胶(Org-ApGltn)作为支撑层和癸酰基修饰的 ApGltn(C10-ApGltn)与季戊四醇聚乙二醇醚四琥珀酰亚胺基戊二酸酯(4S-PEG)作为黏附层组成,命名为 C10-ApGltn 贴剂。C10-ApGltn 贴剂通过 4S-PEG 和 C10-ApGltn 中的疏水性基团的活化,通过形成共价键和物理相互作用黏附在血管表面。通过取代度、4S-PEG 的分子量、C10-ApGltn 的浓度和 NHS/NH 比优化 C10-ApGltn 贴剂的破裂强度。优化后的 C10-ApGltn 贴剂与市售的 TachoSil®相比,破裂强度显著提高。C10-ApGltn 贴剂在胶原酶缓冲溶液中具有酶降解性。在大鼠肝出血模型中,C10-ApGltn 贴剂在出血部位充当密封剂,并表现出与 TachoSil®竞争的止血性能。