Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China.
Stomatologic Hospital and College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui 230032, China.
Acta Biomater. 2023 Sep 1;167:219-233. doi: 10.1016/j.actbio.2023.05.044. Epub 2023 May 29.
Bio-factor stimulation is essential for axonal regeneration in the central nervous system. Thus, persistent and efficient factor delivery in the local microenvironment is an ideal strategy for spinal cord injury repair. We developed a biomimetic hydrogel scaffold to load biofactors in situ and release them in a controlled way as a promising therapeutic modality. Hyaluronic acid and silk fibroin were cross-linked as the basement of the scaffolds, and poly-dopamine coating was used to further increase the loading of factors and endow the hydrogel scaffolds with ideal physical and chemical properties and proper biocompatibility. Notably, neurotrophin-3 release from the hydrogel scaffolds was prolonged to 28 days. A spinal cord injury model was constructed for hydrogel scaffold transplantation. After eight weeks, significant NF200-positive nerve fibers were observed extending across the glial scar to the center of the injured area. Due to the release of neurotrophin-3, spinal cord regeneration was enhanced, and the cavity area of the injury graft site and inflammation associated with CD68 positive cells were reduced, which led to a significant improvement in hind limb motor function. The results show that the hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold achieved locally slow release of neurotrophin-3, thus facilitating the regeneration of injured spinal cord. STATEMENT OF SIGNIFICANCE: Hydrogels have received great attention in spinal cord regeneration. Current research has focused on more efficient and controlled release of bio-factors. Here, we adopted a mussel-inspired strategy to functionalize the hyaluronic acid/silk fibroin hydrogel scaffold to increase the load of neurotrophin-3 and extend the release time. The hydrogel scaffolds have ideal physiochemical properties, proper release rate, and biocompatibility. Owing to the continuous neurotrophin-3 release from implanted scaffolds, cavity formation is reduced, inflammation alleviated, and spinal cord regeneration enhanced, indicating great potential for bio-factor delivery in soft tissue regeneration applications.
生物因子刺激对于中枢神经系统轴突再生至关重要。因此，在局部微环境中持续且高效地输送因子是修复脊髓损伤的理想策略。我们开发了一种仿生水凝胶支架，可原位加载生物因子并以可控的方式释放，是一种很有前途的治疗方式。透明质酸和丝素蛋白交联作为支架的基底，聚多巴胺涂层进一步增加了因子的负载，并赋予水凝胶支架理想的物理化学性质和适当的生物相容性。值得注意的是，神经生长因子-3 从水凝胶支架中的释放时间延长至 28 天。构建了脊髓损伤模型进行水凝胶支架移植。八周后，观察到大量 NF200 阳性神经纤维穿过胶质瘢痕延伸至损伤区域中心。由于神经生长因子-3 的释放，脊髓再生得到增强，损伤移植物部位的腔隙面积和与 CD68 阳性细胞相关的炎症减少，从而显著改善后肢运动功能。结果表明，透明质酸/丝素蛋白/聚多巴胺涂层仿生水凝胶支架实现了神经生长因子-3 的局部缓慢释放，从而促进了损伤脊髓的再生。
水凝胶在脊髓再生中受到了广泛关注。目前的研究集中在更高效和可控的生物因子释放上。在这里，我们采用贻贝启发策略对透明质酸/丝素蛋白水凝胶支架进行功能化，以增加神经生长因子-3 的负载并延长释放时间。水凝胶支架具有理想的物理化学性质、适当的释放速率和生物相容性。由于植入支架中持续释放神经生长因子-3，减少了腔形成，减轻了炎症，增强了脊髓再生，表明其在软组织再生应用中具有很大的生物因子传递潜力。
