Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Wuhan, 430072, China; Department of Kidney Transplantation, Nephropathy Hospital, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
Acta Biomater. 2023 Jul 1;164:240-252. doi: 10.1016/j.actbio.2023.04.015. Epub 2023 Apr 17.
Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. STATEMENT OF SIGNIFICANCE: In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management.
过度的皮肤损伤导致的瘢痕形成会引起瘙痒、疼痛、挛缩、运动障碍和外观不佳。功能性伤口敷料旨在加速伤口愈合并减少瘢痕形成。在这项研究中，我们制备了定向或随机排列的聚己内酯/丝素蛋白电纺纳米纤维膜，负载或不负载洛伐他汀，并评估了它们在特定张力方向下对伤口的瘢痕抑制作用。纳米纤维膜具有良好的控制释放性能、机械性能、亲水性和生物相容性。此外，纳米纤维垂直于伤口张力方向的放置最有效地减少了瘢痕形成（瘢痕面积减少了 66.9%）并促进了体内皮肤再生。其机制与定向纳米纤维在伤口愈合的早期调节胶原组织有关。此外，负载洛伐他汀的纳米纤维抑制了肌成纤维细胞的分化和迁移。张力方向垂直的拓扑线索和洛伐他汀协同抑制机械转导和纤维化进展，进一步减少瘢痕形成。总之，我们的研究可能为提供一种有效的瘢痕预防策略，根据患者伤口的局部机械力方向设计个性化敷料，并且添加洛伐他汀可以进一步抑制瘢痕形成。
在体内，细胞和胶原总是平行于张力方向排列。然而，定向的拓扑线索本身会促进肌成纤维细胞的分化，并加剧瘢痕形成。电纺纳米纤维垂直于伤口张力方向的放置最有效地减少了瘢痕形成并促进了体内皮肤再生。其机制与张力方向垂直的纳米纤维在伤口愈合的早期重新调节胶原组织有关。此外，张力方向垂直的拓扑线索和洛伐他汀可以协同抑制机械转导和纤维化进展，进一步减少瘢痕形成。这项研究证明了结合伤口敷料的拓扑线索和药物将是一种有前途的临床瘢痕管理治疗方法。
