Iwata H, Matsuda S, Mitsuhashi K, Itoh E, Ikada Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
Biomaterials. 1998 Oct;19(20):1869-76. doi: 10.1016/s0142-9612(98)00095-7.
Although fibrin glue has been widely used as a surgical adhesive, its components, fibrinogen and thrombin, obtained from human blood are not completely free from the risk of virus infection due to acquired immune deficiency and hepatitis. Recently, we have reported that a polymer pair composed of gelatin and poly(L-glutamic acid) (PLGA) promptly forms a gel and can firmly bond to soft tissues when crosslinked with the aid of water-soluble carbodiimide (WSC). The present study was undertaken to design a new PLGA-gelatin glue without using WSC. Two kinds of PLGA with molecular weights of 71 and 22 kDa were employed to prepare N-hydroxysuccinimide (NHS) activated derivatives. The NHS-activated PLGA could be synthesized at high yields and was found to be stable for an extended time without losing the ability to crosslink with gelatin when stored under a dry-cold condition. This NHS-activated PLGA could spontaneously form a gel with gelatin in an aqueous solution within a short time, comparable to a commercial fibrin glue, when gelation was allowed to proceed at pH 8.3. The NHS-activated PLGA prepared from PLGA with the molecular weight of 22 kDa could be readily dissolved at high concentrations and its ability to form a gel was maintained for more than 10 min when an acidic 8% NHS-activated PLGA solution was used. The bonding strength of PLGA gelatin glues with natural tissue was higher than that of fibrin glue. These findings strongly suggest that this combination of gelatin and NHS-PLGA is very promising as a surgical adhesive and may possibly replace fibrin glues prepared from human blood components.
尽管纤维蛋白胶已被广泛用作手术粘合剂，但其从人血中获取的成分纤维蛋白原和凝血酶，由于获得性免疫缺陷和肝炎，仍不能完全排除病毒感染风险。最近，我们报道了由明胶和聚（L-谷氨酸）（PLGA）组成的聚合物对在水溶性碳二亚胺（WSC）的辅助下交联时能迅速形成凝胶并牢固地粘附于软组织。本研究旨在设计一种不使用WSC的新型PLGA-明胶胶水。采用两种分子量分别为71 kDa和22 kDa的PLGA制备N-羟基琥珀酰亚胺（NHS）活化衍生物。NHS活化的PLGA能高产率合成，并且发现在干冷条件下储存时能长时间稳定，不会丧失与明胶交联的能力。当在pH 8.3下进行凝胶化时，这种NHS活化的PLGA能在短时间内与明胶在水溶液中自发形成凝胶，与市售纤维蛋白胶相当。由分子量为22 kDa的PLGA制备的NHS活化PLGA能很容易地以高浓度溶解，当使用酸性8%的NHS活化PLGA溶液时，其形成凝胶的能力能保持10分钟以上。PLGA-明胶胶水与天然组织的粘结强度高于纤维蛋白胶。这些发现有力地表明，这种明胶与NHS-PLGA的组合作为手术粘合剂非常有前景，并且可能会取代由人血成分制备的纤维蛋白胶。
