PDF(Pubmed)
Abstract：
Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel\'s porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel\'s efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.
摘要：
角膜新生血管(CNV)是致盲性疾病改变的一个重要属性。现有的药物需要大量输注并且吸收有限。研究安全的新药，功效,方便是至关重要的。在这项研究中,我们开发了一种负载骨形态发生蛋白4（BMP4）的泊洛沙姆氧化海藻酸钠（F127-OSA）热敏水凝胶。14％F127-OSA水凝胶在31-32°C下从溶胶转变为凝胶，这可能会延长眼表的应用时间。水凝胶的多孔结构和均匀分散使药物逐渐释放成为可能。我们使用缝合线诱导的大鼠CNV模型来研究水凝胶抑制CNV的机制。我们发现负载BMP4的F127-OSA水凝胶可以显着减少CNV的长度和面积，减轻角膜水肿，停止异常上皮细胞增殖。水凝胶的功效优于普通溶剂组。此外,BMP4热敏水凝胶修复超微结构，包括微绒毛,细胞间连接，和受损的根尖连接复合体（AJC），提示水凝胶阻止CNV形成的潜在机制。总之,我们的研究表明,负载有BMP4的F127-OSA温敏性水凝胶可以修复角膜上皮AJC,是治疗CNV的一种有前景的新型药物.
