The influence on abdominal adhesions and inflammation in rabbits after exposure to differently charged polypeptides

Background: Abdominal adhesions develop on damaged peritoneal surfaces and constitute a significant health related problem. Previous animal studies have shown promising anti-adhesive effects when administering the polycation α-poly-L-lysine (αPL) and the polyanion poly-L-glutamate (PG) together. The objective of the study was to examine the effect of these differently charged polypeptides when administered by spraying and to evaluate any possible effect on fibrinolysis, fibrosis and inflammation. Methods: Rabbits were treated with PLPG after cecal abrasive surgery and analysis from peritoneal biopsies of active tPa/PAI-1 complex and from peritoneal fluid of IL-6 and active TGFb1 at day 0, 1, 4 and 10 were measured after surgery. Histological specimens were analyzed on day 10 regarding inflammation and fibrosis. Peritoneal adhesions were evaluated by adhesion score. All values were compared to the control group (NaCl). Results: PLPG-treated rabbits had a significant diminished adhesion score on day 10 as compared to the control group (p < 0.005). Significantly reduced collagen depositions on the peritoneum were seen in the PLPG group when evaluating the histological specimens (p < 0.05). No significant differences between the experimental and control groups were seen in peritoneal fluid when analyzing for active protein levels. Conclusion: This is the first study to investigate the effect on key parameters in adhesion formation as well as the preventive effect of the PLPG complex on abdominal adhesions in rabbits and also the first study where administration by spraying the polypeptides was used. PLPG was non-toxic in this setting and without significant differences in adhesion formation parameters and a significant reduction in adhesions was observed. This was verified both macroscopically and histologically.

CATase-immobilized hydrogel platform molded by photo-enzyme coupling polymerization for effectively preventing postoperative abdominal adhesion

Redox homeostasis,which is regulated by enzymes acting as regulatory valves,is crucial for maintaining the proper functioning of biomolecules and a stable microenvironment for physiological processes by modulating the homeostasis of reactive oxygen species(ROS).Antioxidant enzymes in biocatalysis are used in the prevention or treatment of oxidative stress-related disease by counteracting the harmful effects of ROS.However,designing a system that can efficiently immobilize antioxidant enzymes with high catalytic activity and stability is still challenging.Bioinspired by photo-biocatalysis,a novel and effective catalase(CATase)-immobilized hydrogel platform has been developed by the proposed photo-enzymatic coupled radical polymerization strategy of the visible light coupling with the porphyrin-centered CATase.The higher catalytic stability and activity can therefore be achieved due to the preferential polymerization of CATase-immobilized hydrogel platform with a favorable three-dimensional network of enhanced coupling efficacy between light and enzymes.The mechanisms of free radical-initiated polymerization as well as the antioxidant cycle in the photo-CATase coupling system have been explored.Intriguingly,the CATase-immobilized hydrogel platform affords an unprecedented antioxidant ability to scavenge ROS and provide an effective cellular protection mechanism against external oxidative stress.Additionally,the CATase-immobilized hydrogel platform can effectively prevent peritoneal adhesion by reducing the expression of inflammatory cytokines.Therefore,the novel CATase-immobilized hydrogel platform is a potential candidate for physical barriers that effectively prevent postoperative adhesion formation,offering a new anti-adhesion strategy for clinical applications.

氨基酸基防污可注射自融合水凝胶的制备及其在术后防粘连中的应用

设计和制备具有优异防污能力的可注射防粘连材料对预防手术后组织和器官的粘连具有重要的意义.在此,我们将含有羟基的氨基酸衍生物引入水凝胶的制备中,通过N-丙烯酰丝氨酸(ASer)的自由基聚合制备了一种新型的氢键交联水凝胶(PASer).结果发现一个甲基取代基的存在会对分子间氢键相互作用产生明显的影响:与聚(N-丙烯酰苏氨酸)(PAThr)水凝胶相比,PASer水凝胶具有较低的成胶浓度和增强的力学性能.值得一提的是,亲水性羟基使PASer水凝胶能够有效抵抗蛋白质吸附和细胞粘附.PASer水凝胶具有优异的力学性能、可注射性、自融合性、良好的生物相容性和适宜的体内停留时间,符合临床对术后抗粘连材料的要求.体内研究实验结果表明,PASer水凝胶在建立的小鼠腹壁缺损模型中可以有效预防术后腹膜粘连发生.