Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
Biomater Sci. 2017 May 2;5(5):982-989. doi: 10.1039/c6bm00829a.
The aim of this study was the development of an innovative biocompatible sealant composed of Alaska pollock-derived gelatin partially modified with a dodecyl group (C12-ApGltn) and a poly(ethylene glycol)-based crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The burst strength of the developed sealants was measured using porcine aorta and rat lungs. The maximum burst strength of a C12-ApGltn-based sealant against the porcine aorta was 4-fold higher than that of an original ApGltn (Org-ApGltn)-based sealant. No significant increase in the burst strength was observed between C12-ApGltn-based sealants with 4.2 and 8.9 mol% modification ratios. From histological observation after burst strength measurement, tissue tearing was observed when a C12-ApGltn-based sealant was applied. In contrast, the Org-ApGltn-based sealant was peeled away from the aorta surface due to cohesion failure. Similar to the porcine aorta, the burst strength of C12-ApGltn-based sealants applied on a rat lung defect was 3-fold higher than that of an Org-ApGltn-based sealant. The curing time of the C12-ApGltn-based sealant measured by a simple mixing method was shorter (2.6 ± 0.1 s) than that of the Org-ApGltn-based sealant (4.1 ± 0.3 s). The swelling ratio of the C12-ApGltn-based sealant (23.7 ± 3.1) was significantly lower than that of the Org-ApGltn-based sealant (32.3 ± 1.1). The C12-ApGltn-based sealant was completely degraded within 28 days after implantation in the backs of rats without a severe inflammation reaction. However, the Org-ApGltn-based sealant disappeared within 14 days. These results indicated that hydrophobically-modified ApGltn has an effective sealing effect on moist tissues and biocompatibility in vivo.
本研究的目的是开发一种由阿拉斯加鳕鱼衍生明胶部分改性的十二烷基基团(C12-ApGltn)和基于聚乙二醇的交联剂,即五倍子醇聚乙二醇醚四琥珀酰亚胺基戊二酸酯组成的创新型生物相容密封剂。使用猪主动脉和大鼠肺来测量开发的密封剂的破裂强度。C12-ApGltn 基密封剂对猪主动脉的最大破裂强度是原始 ApGltn(Org-ApGltn)基密封剂的 4 倍。改性比为 4.2 和 8.9 mol%的 C12-ApGltn 基密封剂之间的破裂强度没有显著增加。从破裂强度测量后的组织学观察结果来看,当使用 C12-ApGltn 基密封剂时观察到组织撕裂。相比之下,Org-ApGltn 基密封剂由于内聚破坏而从主动脉表面剥落。与猪主动脉相似,应用于大鼠肺缺陷的 C12-ApGltn 基密封剂的破裂强度比 Org-ApGltn 基密封剂高 3 倍。通过简单的混合方法测量的 C12-ApGltn 基密封剂的固化时间(2.6±0.1 s)短于 Org-ApGltn 基密封剂(4.1±0.3 s)。C12-ApGltn 基密封剂的溶胀率(23.7±3.1)明显低于 Org-ApGltn 基密封剂(32.3±1.1)。C12-ApGltn 基密封剂在大鼠背部植入后 28 天内完全降解,没有严重的炎症反应。然而,Org-ApGltn 基密封剂在 14 天内消失。这些结果表明,疏水改性的 ApGltn 对湿润组织具有有效的密封效果,并具有体内生物相容性。