Department of Mechanical Engineering, The University of Utah, 1495 E 100 S, Salt Lake City, UT, 84112, USA.
Department of Surgery, Division of Plastic Surgery, The University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT, 84132, USA.
Biomed Microdevices. 2024 Aug 5;26(3):34. doi: 10.1007/s10544-024-00717-y.
Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.
临界尺寸周围神经损伤构成了重大的临床挑战，导致功能丧失和残疾。目前的再生策略，包括自体移植物、合成神经导管和生物治疗，都面临着一些挑战，例如供应有限、供体部位发病率、恢复效果不佳、潜在的免疫反应以及持续的稳定性和生物活性。周围神经再生的一个障碍是免疫反应，它会导致炎症和瘢痕形成，从而阻碍再生过程。满足免疫和再生的需求对于成功的神经恢复至关重要。在这里，我们介绍了一种新型可生物降解的他克莫司洗脱神经引导导管，由聚（L-丙交酯-共-己内酯）的混合物制成，以促进周围神经再生，并报告了在大鼠坐骨神经 15 毫米临界尺寸间隙中测试这种导管的情况。导管的扩散孔使局部释放具有神经再生特性的强效免疫抑制剂他克莫司直接进入损伤部位。进行了一系列体外实验来评估导管维持可促进神经突生长的受控他克莫司释放曲线的能力。随后在大鼠坐骨神经损伤模型中的体内评估表明，与使用安慰剂导管的对照组相比，神经再生有了显著的增强，表现为轴突生长和功能恢复的改善。这些发现表明，将可生物降解的导管与他克莫司的局部、持续释放相结合具有协同作用，这表明了一种有前途的治疗周围神经损伤的方法。在考虑将其应用于人体之前，需要进一步优化设计和进行长期疗效研究和临床试验。
