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