Histology and Embryology Department, State University of Rio de Janeiro, UERJ, Rio de Janeiro 20950-003, Brazil.
Institute of Chemistry, University of Campinas, UNICAMP, Campinas, 13083-970 SP, Brazil.
Colloids Surf B Biointerfaces. 2015 Jun 1;130:182-91. doi: 10.1016/j.colsurfb.2015.04.007. Epub 2015 Apr 13.
Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing.
一氧化氮（NO）释放生物材料代表了一种用作主动伤口敷料的潜在策略，能够加速伤口愈合。局部释放 NO 的聚乙烯醇（PVA）薄膜和 Pluronic F127 水凝胶（F127）已经显示出有效的皮肤血管扩张和伤口愈合作用。在这项研究中，我们通过用巯基琥珀酸（MSA）和硫乳酸（TLA）的混合物酯化将 SNO 基团功能化到 PVA 薄膜上，然后对 SH 部分进行 S-亚硝化。这些薄膜与底层的聚氧化乙烯-聚氧化丙烯-聚氧化乙烯，即 PEO-PPO-PEO（Pluronic F127）水凝胶结合，并用于动物模型中皮肤损伤的局部治疗。PVA 与 MSA 和 TLA 的混合酯化导致具有高溶胀能力的化学交联 PVA-SNO 薄膜，能够自发释放 NO。实时 NO 释放测量表明，水凝胶层降低了 PVA-SNO 薄膜的初始 NO 爆发。我们证明，PVA-SNO 薄膜与 F127 水凝胶的组合加速了伤口收缩，减少了伤口间隙和细胞密度，并加速了病变的炎症阶段。这些结果反映在疤痕组织中肌纤维母细胞分化和 III 型胶原蛋白表达的增加。因此，PVA-SNO 薄膜与 F127 水凝胶的组合可能代表一种新的用于加速伤口愈合的主动伤口敷料方法。
