Lotfi Roya, Dolatyar Banafsheh, Zandi Nooshin, Tamjid Elnaz, Pourjavadi Ali, Simchi Abdolreza
Institute for Convergence Science & Technology and Department of Materials Science and Engineering, Sharif University of Technology, Tehran 14588-89694, Iran.
Developmental Biology Lab., School of Biology, College of Science, University of Tehran, Tehran, Iran.
Biomater Adv. 2025 May;170:214197. doi: 10.1016/j.bioadv.2025.214197. Epub 2025 Jan 20.
Electroconductive biomaterials, as advanced nerve guidance conduits (NGCs), have shown great promise to accelerate the rate of peripheral nerve repair and regeneration (PNR) but remain among the greatest challenges in regenerative medicine because of frail recovery. Herein, we introduce injectable nanocomposite nerve conduits based on gelatin methacrylate (GelMa) and MXene nanosheets (MX) for PNR. Microstructural studies determine that the addition of MX increases the mean pore size of GelMa NH from 5.8 ± 1.2 μm to 8.4 ± 1.6 μm for the hydrogel containing 0.25 mg/mL MX, for example, leading to higher swelling and degradation rates. The highest electrical conductivity (∼910 μS/cm) is attained for the GelMa-based nanocomposite composed MX with the concentration of 0.125 mg/mL, for the reason that at higher concentrations, agglomeration of the MXs happens. In vitro investigations, including metabolic activity and live-dead assessments by PC12 cells, reveal the biocompatibility of developed nanocomposite hydrogels (NHs) containing different concentrations of MX nanosheets in the range of 0.025-0.25 mg/mL. Implantation of GelMa-MX conduits in a rat model of peripheral nerve injury (PNI) leads to the impressive recovery of the injured sciatic nerve's sensory, motor, and sensory-motor function. Electrophysiological analysis also indicates a significant increase in compound muscle action potential and nerve conduction velocity with a decrease in terminal latency in animals implanted with GelMa-MX conduits compared to control groups (animals implanted with GelMa and animals without implantation). Moreover, histological analysis exhibits a notable absence of fibrous connective tissue in the regenerated nerve fibers with a substantial increase in more organized myelinated axons. Our results demonstrate that GelMa-MX conduits promote regeneration of the injured sciatic nerve and could be promising for peripheral nerve tissue engineering.
导电生物材料作为先进的神经引导导管（NGC），已显示出极大的潜力来加速周围神经修复和再生（PNR）的速度，但由于恢复效果不佳，仍然是再生医学面临的最大挑战之一。在此，我们介绍基于甲基丙烯酸明胶（GelMa）和MXene纳米片（MX）的可注射纳米复合神经导管用于PNR。微观结构研究表明，例如，对于含有0.25mg/mL MX的水凝胶，添加MX会使GelMa NH的平均孔径从5.8±1.2μm增加到8.4±1.6μm，从而导致更高的溶胀和降解速率。对于浓度为0.125mg/mL的由MX组成的基于GelMa的纳米复合材料，可获得最高电导率（约910μS/cm），原因是在较高浓度下，MX会发生团聚。体外研究，包括PC12细胞的代谢活性和活死评估，揭示了含有浓度范围为0.025 - 0.25mg/mL的不同浓度MX纳米片的已开发纳米复合水凝胶（NH）的生物相容性。将GelMa - MX导管植入周围神经损伤（PNI）大鼠模型中，可使受伤坐骨神经的感觉、运动和感觉运动功能得到显著恢复。电生理分析还表明，与对照组（植入GelMa的动物和未植入的动物）相比，植入GelMa - MX导管的动物的复合肌肉动作电位和神经传导速度显著增加，终末潜伏期缩短。此外，组织学分析显示再生神经纤维中明显没有纤维结缔组织，且更有组织的有髓轴突大量增加。我们的结果表明，GelMa - MX导管促进了受伤坐骨神经的再生，有望用于周围神经组织工程。
