Mesh : Alginates / chemistry Gelatin / chemistry Nanofibers / chemistry Wound Healing / drug effects Hydrogels / chemistry pharmacology Animals Mice Bandages Cross-Linking Reagents / chemistry Polyesters / chemistry Regeneration / drug effects Biocompatible Materials / chemistry pharmacology Male

来  源:   DOI:10.1021/acs.biomac.4c00406

Abstract:
Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness in vivo wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.
摘要:
由天然衍生的聚合物制成的伤口敷料因其生物相容性而受到高度重视,生物降解性,和生物功能。然而,天然聚合物基水凝胶可能有自己的局限性,如低机械强度,有限的细胞亲和力,和潜在的细胞毒性的交联剂,划定了它们的使用界限,阻碍了它们的实际应用。为了克服天然衍生聚合物的局限性,这项研究使用氧化的海藻酸盐和明胶与5mg/mL聚己内酯(PCL):明胶纳米纤维碎片的混合物,比例为7:3(OGN-7),以开发可注射的水凝胶复合伤口敷料。通过席夫碱机制,氧化的藻酸盐链与明胶和PCL/明胶纳米纤维的双重交联促进了可修复的水凝胶的原位形成。在纳米纤维的物理整合的支持下,从而避免了对额外交联剂的需要。此外,OGN-7表现出增加的刚度(γ=79.4-316.3%),减少胶凝时间(543±5至475±5s),改善水凝胶的可再填充性,和优良的生物相容性。值得注意的是,OGN-7在孵育1小时内实现完全融合,并在外部应力下保持结构完整性,有效克服天然聚合物敷料固有的机械弱点,增强生物功能。OGN-7的疗效通过全厚度体内伤口愈合分析得到验证,这表明与基于藻酸盐的敷料和对照组相比,OGN-7显着加速了伤口闭合。组织学分析进一步显示,OGN-7组再生皮肤的上皮再形成和胶原沉积显著增强,证实了OGN-7优越的治疗性能。总之,OGN-7优化了天然聚合物的协同效应,这增强了它们作为伤口敷料的集体功能,并扩展了它们在各种生物医学应用中的效用。
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