Noosak Chayanee, Jantorn Pavarish, Surassmo Suvimol, Chukaew Sittichat, Meesane Jirut, Saeloh Sotthibandhu Dennapa
Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, Thailand.
Faculty of Medical Technology, Prince of Songkla University, Songkhla, Thailand.
PLoS One. 2025 Jul 24;20(7):e0328846. doi: 10.1371/journal.pone.0328846. eCollection 2025.
Chronic osteomyelitis, often accompanied by bone loss, requires an adequate angiogenic response for bone regeneration. Loading growth factors into a drug vehicle to promote angiogenesis can address this challenge. In a previous study, we demonstrated the potential of sericin/polyvinyl alcohol (PVA) hydrogel as a functional biomaterial carrier for osteomyelitis treatment. In this study, we optimized sericin/PVA hydrogel for enhanced angiogenesis by supplementing sericin nanoparticles as vascular endothelial growth factor (VEGF) nanocarriers. Sericin nanoparticles, 284.20 ± 13.20 nm in size, exhibited a spherical morphology with 86% VEGF encapsulation efficiency. After integrating VEGF-loaded sericin nanoparticles, the hydrogel was coated with 0.1% and 1% gelatin, and its physical and mechanical properties were assessed. Coating the hydrogel with gelatin enhanced its swelling properties, providing an appropriate degradation rate to support bone regeneration and angiogenesis, and improve mechanical properties. The uncoated hydrogel and hydrogels coated with 0.1% and 1% gelatin exhibited burst release rates of 70%, 60%, and 45% with cumulative release rates on day 14 measured at 76%, 67%, and 57%, respectively. The hydrogels were biocompatible with MC3T3-E1 osteoblastic cell lines and human umbilical vein endothelial cells (HUVEC). The gelatin-coated hydrogels also promoted cell attachment of HUVEC cells. Gelatin-coated hydrogels containing VEGF-loaded sericin nanoparticles were evaluated for their bioactivity on HUVEC cell proliferation. After a 14-day treatment, cell proliferation in 0.1% gelatin-coated hydrogel was significantly higher than in 1% gelatin-coated hydrogel, with over a 160% increase. The expression levels of genes related to angiogenesis were quantitatively examined and results suggested that the hydrogels affected the eNOS pathway to promote angiogenesis. Despite optimization efforts, the sericin/PVA hydrogel maintained effective antibacterial activity against Gram-positive and Gram-negative bacteria. The enhanced sericin/PVA hydrogel showed promise as a novel implant biomaterial for treating chronic osteomyelitis, particularly by promoting angiogenesis.
慢性骨髓炎常伴有骨质流失，骨再生需要充足的血管生成反应。将生长因子负载于药物载体中以促进血管生成可应对这一挑战。在先前的一项研究中，我们证明了丝胶蛋白/聚乙烯醇（PVA）水凝胶作为治疗骨髓炎的功能性生物材料载体的潜力。在本研究中，我们通过补充丝胶纳米颗粒作为血管内皮生长因子（VEGF）纳米载体来优化丝胶蛋白/PVA水凝胶以增强血管生成。丝胶纳米颗粒尺寸为284.20±13.20 nm，呈球形形态，VEGF包封效率为86%。整合负载VEGF的丝胶纳米颗粒后，水凝胶用0.1%和1%的明胶包被，并评估其物理和力学性能。用明胶包被水凝胶增强了其溶胀性能，提供了适当的降解速率以支持骨再生和血管生成，并改善了力学性能。未包被的水凝胶以及用0.1%和1%明胶包被的水凝胶的突释率分别为70%、60%和45%，第14天的累积释放率分别为76%、67%和57%。这些水凝胶与MC3T3 - E1成骨细胞系和人脐静脉内皮细胞（HUVEC）具有生物相容性。明胶包被的水凝胶还促进了HUVEC细胞的附着。对含有负载VEGF的丝胶纳米颗粒的明胶包被水凝胶对HUVEC细胞增殖的生物活性进行了评估。经过14天的处理后，0.1%明胶包被水凝胶中的细胞增殖显著高于1%明胶包被水凝胶中的细胞增殖，增加超过160%。对与血管生成相关的基因表达水平进行了定量检测，结果表明水凝胶影响eNOS途径以促进血管生成。尽管进行了优化努力，丝胶蛋白/PVA水凝胶对革兰氏阳性和革兰氏阴性细菌仍保持有效的抗菌活性。增强后的丝胶蛋白/PVA水凝胶有望成为一种治疗慢性骨髓炎的新型植入生物材料，特别是通过促进血管生成。
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