Deininger Stefanie, Knoll Andreas, Grübel Nadja, Pala Andrej, König Ralph, Wirtz Christian Rainer, Pedro Maria Teresa
Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg, Germany.
Front Cell Dev Biol. 2025 Sep 11;13:1603678. doi: 10.3389/fcell.2025.1603678. eCollection 2025.
Peripheral nerve injuries remain challenging due to the limited regenerative capacity over long distances and the complexity of repair mechanisms. While autologous nerve grafts are the clinical gold standard, their use is restricted by donor-site morbidity and tissue availability. Tissue-engineered materials such as nerve guidance conduits (NGCs), hydrogels, and bioactive scaffolds offer alternative solutions by providing structural support and delivering trophic, immunomodulatory, or electrical cues. This mini-review categorizes these materials by their functional properties, including drug delivery, cell integration, and electroactivity, and critically assesses their preclinical performance and translational limitations. Natural materials such as collagen and chitosan exhibit good biocompatibility but limited mechanical stability and variability. Synthetic polymers and electroactive materials allow for customization and controlled stimulation but often provoke immune responses or degrade into harmful byproducts. Advanced drug-delivery systems using hydrogels and microspheres enable targeted factor release, yet reproducibility and kinetics remain critical barriers. Cell-integrated constructs, including Schwann cell-like cells and engineered neural tissue, offer high regenerative potential but face challenges in scalability, regulatory classification, and manufacturing. Importantly, many preclinical studies do not benchmark against autografts or address neuroma formation, fibrosis, and delayed regeneration-key issues in human lesions. A summary of preclinical constructs and translational barriers is provided to highlight recurring obstacles such as immune incompatibility, insufficient vascular integration, and regulatory hurdles. Future research must refine model systems, align regulatory strategies, and enhance construct functionality to enable effective clinical translation.
由于长距离再生能力有限以及修复机制的复杂性,周围神经损伤仍然具有挑战性。虽然自体神经移植是临床金标准,但其应用受到供体部位发病率和组织可用性的限制。组织工程材料,如神经引导导管(NGC)、水凝胶和生物活性支架,通过提供结构支持并传递营养、免疫调节或电信号,提供了替代解决方案。本综述根据其功能特性对这些材料进行分类,包括药物递送、细胞整合和电活性,并严格评估其临床前性能和转化局限性。胶原蛋白和壳聚糖等天然材料具有良好的生物相容性,但机械稳定性和可变性有限。合成聚合物和电活性材料允许定制和可控刺激,但往往会引发免疫反应或降解为有害副产物。使用水凝胶和微球的先进药物递送系统能够实现靶向因子释放,但可重复性和动力学仍然是关键障碍。细胞整合构建体,包括雪旺氏细胞样细胞和工程化神经组织,具有很高的再生潜力,但在可扩展性、监管分类和制造方面面临挑战。重要的是,许多临床前研究没有与自体移植进行对比,也没有解决神经瘤形成、纤维化和再生延迟等人类损伤中的关键问题。提供了临床前构建体和转化障碍的总结,以突出反复出现的障碍,如免疫不相容、血管整合不足和监管障碍。未来的研究必须改进模型系统、调整监管策略并增强构建体功能,以实现有效的临床转化。