新型可生物降解的组织可黏附材料的合成与表征

Synthesis and Characterization of New Biodegradable Tissue Adhesive Materials

设计合成了一类可聚合固化且具有良好生物降解性能的组织黏附材料。材料使用前为单体分子,常温下呈液态,单体结构含有寡聚乳酸(OLA)片段和氰基丙烯酸酯(CA)官能团。在接触到肌体组织时,单体可通过CA官能团发生分子间聚合形成梳状聚合物并产生黏附。聚合物中的OLA侧链结构可赋予其良好的生物相容性和可降解性。合成了OLA末端分别为羧基或苄基的两种单体(OLA_(4)-CA和OLA_(4)B-CA),通过核磁氢谱鉴定了单体化学结构,采用剪切拉伸强度和固化时间表征组织黏附能力,利用凝胶渗透色谱测试聚合物分子量,在体内、外模型中评价聚合物的降解性能,通过植入试验研究聚合物的生物相容性,此外,采用体外抑菌圈试验测试了材料的抑菌性能。试验结果表明:成功合成了目标单体;单体接触肌体组织可在3 min内聚合固化并产生有效的黏附能力;聚合物的降解性能与侧链OLA片段的末端羧基结构相关;优选的OLA_(4)-CA的聚合物在小鼠体内植入模型中12 h左右即被完全降解吸收,且具有良好的生物相容性;此外,在体外抑菌试验中,材料显示出浓度依赖性的抑菌能力。这类可聚合固化材料有望进一步用于新型创伤敷料和组织粘附材料的开发。

This paper designed and synthesized a kind of polymerizable and curable tissue adhesive materials with good biodegradability.The material is a monomer molecule before use,and it is liquid at room temperature.The monomer structure is composed of monomeric oligolactic acid(OLA)fragments and cyanoacrylate(CA)functional groups.When coming into contact with body tissues,monomers can undergo intermolecular polymerization through CA functional groups to form comb polymers and produce adhesion.The OLA side chain structure in the polymer can give good biocompatibility and degradability.Two monomers,OLA_(4)-CA and OLA_(4)B-CA,with carboxyl or benzyl groups at the ends of OLA were synthesized.The chemical structure of the monomers was determined by ^(1)H nuclear magnetic resonance spectroscopy,and the shear tensile strength and curing times were used to characterize tissue adhesion.Polymer molecular weight and polymer degradation in vivo and in vitro was analyzed by gel permeation chromatography,with biocompatibility determined using implantation tests.In addition,the bacteriostatic properties of the material were tested by inhibition zone test in vitro.The results show that the target monomer is synthesized successfully and the synthesized monomer polymerized and solidified within 3 min following tissue contact and produced effective adhesion.Degradation of the polymer was related to the terminal carboxyl structure of the side chain OLA segment,with the preferred OLA_(4)-CA polymer completely degraded and absorbed within 12 h after implantation in a mouse model;this indicated good biocompatibility.In addition,the in vitro inhibition zone test showed concentration-dependent antibacterial activity of material.This polymerizable material is expected to be used in the development of new wound dressings and tissue adhesive materials.