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含有儿茶酚修饰透明质酸和聚-L-赖氨酸的复合组织粘合剂

Composite Tissue Adhesive Containing Catechol-Modified Hyaluronic Acid and Poly-l-lysine.

作者信息

Zhou Ying, Kang Lingzhi, Yue Zhilian, Liu Xiao, Wallace Gordon G

机构信息

ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, New South Wales 2522, Australia.

出版信息

ACS Appl Bio Mater. 2020 Jan 21;3(1):628-638. doi: 10.1021/acsabm.9b01003. Epub 2019 Dec 11.

DOI:10.1021/acsabm.9b01003
PMID:35019407
Abstract

Commercial tissue adhesives such as fibrin, albumin-glutaraldehyde, and cyanoacrylates often suffer from the limitations of adverse inflammatory reactions, lack of bioactivity, and/or weak wet adhesion. There is a need to develop advanced tissue adhesives which possess adequate wet adhesion and appropriate biodegradability and biocompatibility. The wet adhesion of the catechol group to a variety of substrates is well-known. Further, it undergoes Michael addition with an amine or thiol group, which makes catechol-containing polymers appealing as tissue adhesives because there are abundant amine and thiol groups in native tissue. We present here a composite tissue adhesive based on a catechol-modified polymer that utilizes poly-l-lysine (PLL) as a bridging molecule to promote the interfacing with cells and tissues. Hyaluronic acid (HA) was chosen here as the polymer backbone for functionalization with catechol moieties, which is attributable to its multiple biological activities. The cross-linking conditions of catechol-functionalized HA (HACA) were optimized, and the swelling and degradation behavior of the cross-linked hydrogels were characterized. The PLL/HACA-based adhesive demonstrated good adhesion to hydrogels derived from collagen and gelatin that act as a simplified soft tissue model, and to porcine skin tissue. Moreover, the adhesive supported culture of a human umbilical vein endothelial cell line (HUV-EC-C) with high cell viability and formation of capillary-like structure. This may bring added benefit by means of promoting angiogenesis, therefore promoting the integration between host tissue and implant. Our results indicate that PLL/HACA could be a promising tissue adhesive for multiple internal uses.

摘要

诸如纤维蛋白、白蛋白-戊二醛和氰基丙烯酸酯等商业组织粘合剂常常存在不良炎症反应、缺乏生物活性和/或湿粘附力弱等局限性。因此,需要开发具有足够湿粘附力、适当的生物降解性和生物相容性的先进组织粘合剂。儿茶酚基团对多种底物的湿粘附力是众所周知的。此外,它能与胺基或硫醇基团发生迈克尔加成反应,这使得含儿茶酚的聚合物作为组织粘合剂具有吸引力,因为天然组织中存在大量的胺基和硫醇基团。我们在此展示一种基于儿茶酚改性聚合物的复合组织粘合剂,该粘合剂利用聚-L-赖氨酸(PLL)作为桥接分子来促进与细胞和组织的界面结合。这里选择透明质酸(HA)作为用于儿茶酚部分功能化的聚合物主链,这归因于其多种生物活性。优化了儿茶酚功能化HA(HACA)的交联条件,并对交联水凝胶的溶胀和降解行为进行了表征。基于PLL/HACA的粘合剂对源自胶原蛋白和明胶的水凝胶(作为简化的软组织模型)以及猪皮肤组织表现出良好的粘附力。此外,该粘合剂支持人脐静脉内皮细胞系(HUV-EC-C)的培养,细胞活力高且形成毛细血管样结构。这可能通过促进血管生成带来额外益处,从而促进宿主组织与植入物之间的整合。我们的结果表明,PLL/HACA可能是一种有前途的用于多种内部用途的组织粘合剂。

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