Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Centre for the Study of Pain, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada.
Biomaterials. 2022 Oct;289:121764. doi: 10.1016/j.biomaterials.2022.121764. Epub 2022 Aug 26.
Peripheral nerve innervation is essential for regulating tissue repair and regeneration. MAA-based biomaterials have been previously shown to promote angiogenesis. Here we show a new role for MAA-based biomaterials in promoting terminal axon nerve growth. Our results demonstrate that MAA-based biomaterials promote peripheral nerve growth in an Igf-1 and Shh dependent manner. The resulting nerves increased the sensitivity of treated mice paws to nociception. iDISCO clearing showed that MAA increased the presence of peripheral nerve structures in whole explants. MAA was also able to increase the expression of key neuronal markers and growth factors in a peripheral neuropathy model, the diabetic db/db mouse, suggesting that MAA-based biomaterials may be relevant to treatment of peripheral neuropathy. Moreover, in a peripheral neuropathy model, MAA was able to up-regulate the expression of growth factors for an extended duration suggesting MAA may prevent degeneration through an effect on factors that promote survival. As all tissues are innervated, MAA-based biomaterials could have broad applications in the promoting regeneration and preventing degeneration of peripheral nerves.
周围神经支配对于调节组织修复和再生至关重要。基于 MAA 的生物材料先前已被证明可促进血管生成。在这里，我们展示了基于 MAA 的生物材料在促进终末轴突神经生长方面的新作用。我们的研究结果表明，基于 MAA 的生物材料以 Igf-1 和 Shh 依赖的方式促进周围神经生长。由此产生的神经增加了接受治疗的小鼠爪子对伤害性感受的敏感性。iDISCO 清除显示 MAA 增加了整个外植体中周围神经结构的存在。MAA 还能够在周围神经病变模型（糖尿病 db/db 小鼠）中增加关键神经元标记物和生长因子的表达，这表明基于 MAA 的生物材料可能与治疗周围神经病变有关。此外，在周围神经病变模型中，MAA 能够延长生长因子的表达上调时间，这表明 MAA 可能通过影响促进存活的因子来防止退化。由于所有组织都有神经支配，因此基于 MAA 的生物材料可能具有广泛的应用前景，可促进周围神经的再生和防止其退化。
