{"title":"用于抑制腱周粘连的双嘧达莫接枝共聚物电纺纳米纤维膜","authors":"Xinqi Zeng, Yanhao Li, Gang Zhao, Xiaoer Wei, Rongpu Wu, Sa Pang, Yuange Li, Zaijing Tao, Shuo Wang, Jixian Yue, Xu Chen, Yajun Xu, Yongjun Rui, Jingyi Mi, Yang Liu, Jinglei Wu, Jian Tian","doi":"10.1016/j.actbio.2024.09.031","DOIUrl":null,"url":null,"abstract":"<p><p>Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)-dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. STATEMENT OF SIGNIFICANCE: Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions.\",\"authors\":\"Xinqi Zeng, Yanhao Li, Gang Zhao, Xiaoer Wei, Rongpu Wu, Sa Pang, Yuange Li, Zaijing Tao, Shuo Wang, Jixian Yue, Xu Chen, Yajun Xu, Yongjun Rui, Jingyi Mi, Yang Liu, Jinglei Wu, Jian Tian\",\"doi\":\"10.1016/j.actbio.2024.09.031\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)-dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. STATEMENT OF SIGNIFICANCE: Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.</p>\",\"PeriodicalId\":93848,\"journal\":{\"name\":\"Acta biomaterialia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta biomaterialia\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.actbio.2024.09.031\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta biomaterialia","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.actbio.2024.09.031","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
创伤后肌腱粘连严重影响患者的预后和生活质量,主要原因是临床上缺乏有效的预防和治疗措施。目前的治疗方法,包括手术切除和非甾体类抗炎药物,经常显示出有限的疗效或导致严重的副作用。因此,使用抗粘连屏障进行药物输送并植入损伤部位以解决腱周粘连(PA)问题已引起广泛关注。电纺纳米纤维膜(ENM)已被广泛用作药物输送平台。在这项研究中,我们制作了一种名为 PLC-DP 的聚乳酸(PLA)-双嘧达莫(DP)接枝共聚物 ENM。与传统的药物负载 ENM 相比,这种膜具有酶敏感特性,能更可控、更持久地释放药物。在实验中,与对照组相比,PLC-DP 植入能将组织粘附性降低 47%,同时不会对肌腱愈合产生不利影响。从机理上讲,PLC-DP 能有效激活含 FXYD 域的离子传输调节器 2(FXYD2)蛋白,从而下调成纤维细胞转化生长因子 beta(TGF-β)/Smad3 信号通路。PLC-DP 充分利用了 DP 的抗粘连特性和接枝共聚物的酶敏感特性,为未来临床治疗和预防 PA 提供了一种前景广阔的方法。意义说明:腱周粘连(PA)是一种常见的致残性疾病,严重影响创伤后患者的预后和生活质量。目前的治疗方法往往疗效有限或存在严重的副作用,给临床实践留下了严重的空白。我们开发了一种专门用于抑制 PA 的重要生物材料--聚(乳酸)-双嘧达莫接枝共聚物电纺纳米纤维膜(PLC-DP)。与传统的药物负载型电纺纳米纤维膜不同,PLC-DPs 具有酶敏感的药物特性,可按需持续释放药物。我们的实验表明,植入 PLC-DP 能有效减少 47% 的组织粘连,且不影响肌腱愈合。我们阐明了这一现象背后的机制,认为 PCD 激活 FXYD2 以抑制 TGF-β 诱导的 Col III 的表达,而 Col III 是 PA 发育的关键因素。
Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions.
Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)-dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. STATEMENT OF SIGNIFICANCE: Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.