Key Laboratory for Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology, 130# Meilong Road, Shanghai 200237, China; Institute of Microsurgery on Extremities, Institute of Orthopaedic Surgery, Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People' Hospital, 600# Yishan Road, Shanghai 200233, China.
Institute of Microsurgery on Extremities, Institute of Orthopaedic Surgery, Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People' Hospital, 600# Yishan Road, Shanghai 200233, China.
Acta Biomater. 2017 Oct 15;62:199-209. doi: 10.1016/j.actbio.2017.08.047. Epub 2017 Sep 1.
Postoperative adhesion is a serious complication that can further lead to morbidity and/or mortality. Polymer anti-adhesion barrier material provides an effective precaution to reduce the probability of postoperative adhesion. Clinical application requires these materials to be easily handled, biocompatible, biodegradable, and most importantly tissue adherent to provide target sites with reliable isolation. However, currently there is nearly no polymer barrier material that can fully satisfy these requirements. In this study, based on the photoinduced imine-crosslinking (PIC) reaction, we had developed a photo-crosslinking hydrogel (CNG hydrogel) that composed of o-nitrobenzyl alcohol (NB) modified carboxymethyl cellulose (CMC-NB) and glycol chitosan (GC) as an anti-adhesion barrier material. Under light irradiation, CMC-NB generated aldehyde groups which subsequently reacted with amino groups distributed on GC or tissue surface to form a hydrogel barrier that covalently attached to tissue surface. Rheological analysis demonstrated that CNG hydrogel (30mg/mL polymer content) could be formed in 30s upon light irradiation. Tissue adhesive tests showed that the tissue adhesive strength of CNG hydrogel (30mg/mL) was about 8.32kPa-24.65kPa which increased with increasing CMC-NB content in CNG hydrogel. Toxicity evaluation by L929 cells demonstrated that CNG hydrogel was cytocompatible. Furthermore, sidewall defect-cecum abrasion model of rat was employed to evaluate the postoperative anti-adhesion efficacy of CNG hydrogel. And a significantly reduction of tissue adhesion (20% samples with low score adhesion) was found in CNG hydrogel treated group, compared with control group (100% samples with high score adhesion). In addition, CNG hydrogel could be degraded in nearly 14days and showed no side effect on wound healing. These findings indicated that CNG hydrogel can effectively expanded the clinical treatments of postoperative tissue adhesion.
In this study, a tissue adhesive photo-crosslinking hydrogel (CNG) was developed based on photo-induced imine crosslinking reaction (PIC) for postoperative anti-adhesion. CNG hydrogel showed the features of easy and convenient operation, fast and controllable gelation, suitable gel strength, good biocompatibility, and most importantly strong tissue adhesiveness. Therefore, it shows very high performance to prevent postoperative tissue adhesion. Overall, our study provides a more suitable hydrogel barrier material that can overcome the shortcomings of current barriers for clinical postoperative anti-adhesion.
背景:术后粘连是一种严重的并发症,可进一步导致发病率和/或死亡率。聚合物防粘连屏障材料提供了一种有效的预防措施,可降低术后粘连的概率。临床应用要求这些材料易于操作、具有生物相容性、可生物降解,最重要的是与组织粘附,从而为目标部位提供可靠的隔离。然而,目前几乎没有聚合物屏障材料能够完全满足这些要求。在本研究中,我们基于光诱导亚胺交联(PIC)反应,开发了一种由邻硝基苄基醇(NB)改性羧甲基纤维素(CMC-NB)和乙二醇壳聚糖(GC)组成的光交联水凝胶(CNG 水凝胶)作为防粘连屏障材料。在光照射下,CMC-NB 产生醛基,随后与 GC 或组织表面上分布的氨基反应,形成共价连接到组织表面的水凝胶屏障。流变分析表明,光照射 30s 即可形成 CNG 水凝胶(聚合物含量 30mg/mL)。组织粘合测试表明,CNG 水凝胶(30mg/mL)的组织粘合强度约为 8.32kPa-24.65kPa,随着 CNG 水凝胶中 CMC-NB 含量的增加而增加。通过 L929 细胞进行的毒性评估表明 CNG 水凝胶具有细胞相容性。此外,还采用大鼠侧壁缺陷-盲肠磨损模型评估了 CNG 水凝胶的术后防粘连效果。与对照组(100%高评分粘连样品)相比,在 CNG 水凝胶处理组中发现组织粘连明显减少(20%样品粘连评分低)。此外,CNG 水凝胶在近 14 天内降解,对伤口愈合无副作用。这些发现表明 CNG 水凝胶可有效扩大术后组织粘连的临床治疗范围。
意义:本研究基于光诱导亚胺交联反应(PIC)开发了一种组织胶粘剂光交联水凝胶(CNG),用于术后防粘连。CNG 水凝胶具有操作简便、快速可控凝胶化、凝胶强度适宜、生物相容性好、最重要的是与组织粘附性强等特点。因此,它在预防术后组织粘连方面表现出非常高的性能。总体而言,我们的研究提供了一种更合适的水凝胶屏障材料,可以克服当前用于临床术后防粘连的屏障材料的缺点。