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快速成型、强力黏附且负载去铁胺的真菌源壳聚糖水凝胶用于无缝合短间隙周围神经修复

Rapid Forming, Robust Adhesive Fungal-Sourced Chitosan Hydrogels Loaded with Deferoxamine for Sutureless Short-Gap Peripheral Nerve Repair.

作者信息

Dong Qi, Shi Kai, Ai Junjie, Yang Junfeng, Yang Kaidan, Chen Ruina, Wang Yachao, Zhou Yingshan

机构信息

State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan, 430073, P. R. China.

College of Materials Science and Engineering, Wuhan Textile University, Wuhan, 430073, P. R. China.

出版信息

Adv Healthc Mater. 2024 Dec;13(31):e2401412. doi: 10.1002/adhm.202401412. Epub 2024 Sep 13.

DOI:10.1002/adhm.202401412
PMID:39268836
Abstract

Clinically, conventional sutures for repair of short-distance nerve injuries (< 5 mm) may contribute to uncontrolled inflammation and scar formation, thus negatively impacting nerve regeneration. To repair transected peripheral nerves with short distances, a rapid-forming, robust adhesive chitosan hydrogel is prepared by synthesizing maleic and dopamine bi-functionalized fungal-sourced chitosan (DM) and subsequently photopolymerizing DM precursor solution. The hydrogel rapidly polymerized under UV light irradiation (≈2 s) and possessed a strong adhesive strength (273.33 ± 55.07 kPa), facilitating a fast bonding of nerve stump. Especially, its tailored degradation profile over 28 days supported both early gap bridging and subsequent nerve regeneration. Furthermore, deferoxamine (DFO), a pro-angiogenic drug, is loaded into the hydrogel to reach sustainable release, accelerating axonal growth synergistically. A 3 mm long sciatic nerve defects model in rats is used to investigate the efficacy of DM@DFO hydrogel for repairing peripheral nerve defects. After 60 days, the DM@DFO hydrogel significantly outperformed conventional sutures and fibrin glue, improving motor and sensory recovery by reducing inflammation, inhibiting scar formation, and accelerating vascular regeneration within 14 days post-repair. This work highlights the DM@DFO hydrogel as a promising tissue adhesive for effective short-distance peripheral nerve repair.

摘要

临床上,用于修复短距离神经损伤(<5毫米)的传统缝线可能会导致炎症失控和瘢痕形成,从而对神经再生产生负面影响。为了修复短距离横断的周围神经,通过合成马来酸和多巴胺双功能化的真菌源壳聚糖(DM),随后对DM前体溶液进行光聚合,制备了一种快速成型、坚固的粘性壳聚糖水凝胶。该水凝胶在紫外光照射下(约2秒)迅速聚合,具有很强的粘附强度(273.33±55.07千帕),有利于神经残端的快速粘合。特别是,其在28天内定制的降解曲线既支持早期间隙桥接,又支持随后的神经再生。此外,将促血管生成药物去铁胺(DFO)负载到水凝胶中以实现持续释放,协同加速轴突生长。使用大鼠3毫米长的坐骨神经缺损模型来研究DM@DFO水凝胶修复周围神经缺损的效果。60天后,DM@DFO水凝胶明显优于传统缝线和纤维蛋白胶,通过在修复后14天内减轻炎症、抑制瘢痕形成和加速血管再生,改善了运动和感觉恢复。这项工作突出了DM@DFO水凝胶作为一种有前景的组织粘合剂用于有效的短距离周围神经修复。

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