Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), 291 University Rd, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), 291 University Rd, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Adv Healthc Mater. 2019 Jul;8(14):e1900275. doi: 10.1002/adhm.201900275. Epub 2019 May 15.
Chitosan-catechol, inspired from mussel-adhesive-proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan-catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan-catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol-conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan-catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan-catechol and glycol chitosan-catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan-catechol significantly attenuates the immune response compared with chitosan-catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan-catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan-catechol. This study suggests that glycol chitosan-catechol can be a promising alternative to chitosan-catechol in various biomedical fields such as hemostatic agents.
壳聚糖-儿茶酚，灵感来自贻贝类黏附蛋白，其特点是通过与血清蛋白的即时结合形成黏附膜复合物，而这些血清蛋白在壳聚糖中不存在。利用这一固有特性，壳聚糖-儿茶酚被广泛应用于止血针、一般止血材料、纳米粒子复合材料和 3D 打印。尽管具有多功能性，但由于其不理想的免疫反应，壳聚糖-儿茶酚在临床上的实际应用受到限制。在此，提出了一种儿茶酚修饰的乙二醇壳聚糖作为替代止血水凝胶，其具有可忽略的免疫反应，能够替代壳聚糖-儿茶酚。评估了壳聚糖-儿茶酚和乙二醇壳聚糖-儿茶酚的细胞毒性和体内皮肤刺激性。通过将其皮下植入小鼠后进行组织学分析，评估它们的免疫反应。结果表明，与壳聚糖-儿茶酚相比，乙二醇壳聚糖-儿茶酚显著减弱了免疫反应；这一发现可能归因于乙二醇基团的抗生物污损作用和免疫细胞的减少黏附。最后，乙二醇壳聚糖-儿茶酚水凝胶的组织黏附和止血能力表明，与非乙二醇壳聚糖-儿茶酚相比，这些乙二醇基团对其黏附性和止血能力的影响不大。本研究表明，乙二醇壳聚糖-儿茶酚可以成为壳聚糖-儿茶酚在止血剂等各种生物医学领域的有前途的替代品。
