Biocompatibility and features of degradation of polymer anti-adjection membranes with antibacterial activity

Y. Kudryavtseva, A. Y. Kanonykina, N. A. Efremova, V. A. Koshelev
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Abstract

When performing operations on the abdominal and thoracic organs, the main share of postoperative complications is represented by the formation of adhesions or the development of an infectious process, which leads to a decrease in the quality of life of patients, the need for reoperation and often causes deaths. A solution to this problem can be the use of intraoperative biodegradable anti-adhesion membranes that have their own antibacterial activity.Aim. Development of polymer anti-adhesion membranes with their own anti-inflammatory and antibacterial activity, assessment of their biocompatibility and biodegradation in in vivo experimentsMaterials and Methods. The membranes are made by electrospinning from a composition of biodegradable polymers: polylactide-co-glycolide copolymer (50:50) and polylactide-co-glycolide (85:15). To impart antibacterial properties to the membrane, the antibiotic Tigacil was added to the polymer solution in various dosages - 0.125; 0.25 and 0.5 mg/ml polymer solution. The antibacterial activity of the membranes in vivo was assessed. The physical and mechanical properties were studied and the surface structure of the membranes was assessed using a scanning electron microscope. Biocompatibility and dynamics of biodegradation were assessed in vivo by implantation into laboratory animals (rats) for periods of 14 days, 1, 2 and 3 months, followed by histological examination of explanted samples.Results. Polymer membranes made by electrospinning, without the inclusion of Tigacil, consist of threads whose thickness was 1.63 microns (1.422.85 microns); when Tigacil is included in the fiber composition, the fiber thickness decreases to 1.2 microns (0.977 - 1.89 pm), while the threads are more densely and orderly located. The strength and elasticity modulus of membranes with Tigacil are almost 2 times higher than those of samples without the inclusion of the drug. The maximum antibacterial effect was achieved at a Tigacil dosage of 0.5 mg/ml - the zone of inhibition of Staphylococcus aureus at a Tigacil concentration of 0.125 mg/ ml was 146%, 0.25 mg/ml - 152% and at a concentration of 0.5 mg/ml - 11 .5 mm 177%. The inclusion of Tigacil led to a decrease in the rate of biodegradation of samples in vivo. The samples underwent biodegradation without signs of acute and chronic inflammation.Conclusion. The inclusion of Tigacil in the membrane gives it antibacterial properties, and the optimal concentration of Tigacil was 0.5 mg/ml of the polymer solution. The inclusion of Tigacil in the polymer composition affects the morphology of the membranes, increases the strength and elastic modulus, which led to a decrease in the rate of degradation when implanted subcutaneously in rats. The absence of signs of inflammation confirms the biocompatibility of the developed membranes.
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具有抗菌活性的聚合物抗注射膜的生物相容性和降解特征
在对腹部和胸部器官进行手术时,术后并发症的主要部分是粘连的形成或感染过程的发展,这导致患者生活质量下降,需要再次手术,并经常造成死亡。解决这一问题的办法是使用术中可生物降解的防粘连膜,这种膜本身具有抗菌活性。开发具有自身消炎和抗菌活性的聚合物防粘膜,在体内实验中评估其生物相容性和生物降解性。这种膜是由生物可降解聚合物(聚乳酸-聚乙二醇共聚物(50:50)和聚乳酸-聚乙二醇(85:15))通过电纺丝制成的。为了使膜具有抗菌特性,在聚合物溶液中添加了抗生素 Tigacil,添加量分别为 0.125、0.25 和 0.5 mg/ml。对膜的体内抗菌活性进行了评估。研究了膜的物理和机械性能,并使用扫描电子显微镜评估了膜的表面结构。通过植入实验动物(大鼠)体内 14 天、1 个月、2 个月和 3 个月,对生物相容性和生物降解动态进行了评估,随后对取出的样本进行了组织学检查。电纺丝制成的聚合物膜在不加入替加西尔的情况下,由厚度为 1.63 微米(1.422.85 微米)的丝线组成;在纤维成分中加入替加西尔后,纤维厚度减少到 1.2 微米(0.977 - 1.89 pm),而丝线的分布更加密集有序。添加了 Tigacil 的膜的强度和弹性模量比未添加药物的样品高出近 2 倍。当 Tigacil 的用量为 0.5 mg/ml 时,抗菌效果最佳--Tigacil 浓度为 0.125 mg/ml 时,金黄色葡萄球菌的抑制区为 146%,0.25 mg/ml 时为 152%,0.5 mg/ml 时为 11.5 mm,177%。加入替加西尔会降低样品在体内的生物降解率。样品在生物降解过程中没有出现急性和慢性炎症的迹象。在膜中加入替加西尔可使其具有抗菌特性,替加西尔的最佳浓度为聚合物溶液的 0.5 毫克/毫升。在聚合物成分中加入替加嘧啶会影响膜的形态,增加膜的强度和弹性模量,从而降低植入大鼠皮下的降解率。没有炎症迹象证实了所开发薄膜的生物相容性。
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