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富含血小板的可注射、稳定和可生物降解的水凝胶,由 l-丝氨酸和海藻酸钠诱导,用于有效治疗宫腔粘连。

Injectable, stable, and biodegradable hydrogel with platelet-rich plasma induced by l-serine and sodium alginate for effective treatment of intrauterine adhesions.

机构信息

College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, China.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Int J Biol Macromol. 2024 Jun;270(Pt 1):132363. doi: 10.1016/j.ijbiomac.2024.132363. Epub 2024 May 14.

DOI:10.1016/j.ijbiomac.2024.132363
PMID:38754675
Abstract

The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l-serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l-Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.

摘要

联合药物治疗和物理屏障疗法是治疗宫腔粘连(IUAs)的一种极具前景的策略,但目前缺乏一种合适的支架,该支架需要具备良好的可注射性、适当的机械稳定性和可降解性、优异的生物相容性以及无毒、无排斥的治疗药物。为了解决这个问题,开发了一种新型可注射、可降解的水凝胶,由聚乙二醇二丙烯酸酯(PEGDA)、海藻酸钠(SA)和 l-丝氨酸组成,并负载富含血小板的血浆(PRP)(称为 PSL-PRP),用于治疗 IUAs。l-丝氨酸在 1 分钟内诱导快速凝胶化,并增强水凝胶的机械性能,而可降解的 SA 则为水凝胶提供强度、韧性和适当的降解能力。因此,该水凝胶为 PRP 中生长因子的持续释放提供了一个极好的支架,并起到有效的物理屏障作用。使用 IUAs 大鼠模型进行的体内测试表明,PSL-PRP 水凝胶的原位注射可显著减少纤维化并促进子宫内膜再生,最终恢复生育能力。联合优势使 PSL-PRP 水凝胶在 IUAs 治疗和预防其他内部组织创伤粘连方面极具前景。

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