Harley-Troxell Meaghan E, Pedersen Alisha P, Newby Steven D, Christoph Eli, Stephenson Stacy, Masi Thomas J, Crouch Dustin L, Anderson David E, Dhar Madhu
Tissue Engineering and Regenerative Medicine Laboratory, Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, 37996, USA.
Plastic and Reconstructive Surgery, University of Tennessee Medical Center, Knoxville, TN, 37920, USA.
Int J Nanomedicine. 2025 Mar 13;20:3201-3217. doi: 10.2147/IJN.S501241. eCollection 2025.
Peripheral nerve injuries (PNIs) impact the quality of life of millions of people. The current gold standard of treatment, the autograft, fails to restore nerve function and is often associated with untoward effects. The alternative interventions available remain unable to ensure full functional recovery. For this study we developed a 3D printed nerve guidance conduit (NGC) composed of poly (lactic-co-glycolic acid) (PLGA) and 0.25% graphene oxide (GO), that can be seeded with human adipose-derived mesenchymal stem cells (MSCs), to develop a more effective treatment for PNI.
We evaluated material degradation, surface topography, and MSC attachment in vitro. For the in vivo analyses, a 10-mm long sciatic nerve defect model was created, and rats were randomly divided into 4 treatment groups: autograft, PLGA, PLGA/GO, and PLGA/GO with 1×10 MSCs. For a 6-month period: biomechanics were evaluated using a pressure mat walkway to determine functional repair; systemic toxicity was evaluated using transmission electron microscopy of kidney and lung tissue; immunohistochemistry evaluated local adverse effects, myelin sheath and axonal repair; and gross muscle analyses of the lateral gastrocnemius, medial gastrocnemius, and soleus evaluated muscle reinnervation.
In vitro results showed expected degradation rates, and the addition of GO exhibited cytocompatibility and favorable cell attachment. In vivo results showed biocompatibility with no translocation of the graphene nanoparticles. Histology showed evidence of axonal and myelin sheath repair. Biomechanics and gross muscle analyses had contradicting evidence of functional repair with the addition of GO. No differences were seen with the addition of MSCs.
Our novel PLGA/GO NGC, both with and without MSCs, showed results comparable to or greater than the current gold standard, as well as ease of use surgically. With further studies to validate functional recovery, this specific combination of PLGA and GO may provide an effective biomimetic therapy to repair PNIs.
周围神经损伤（PNIs）影响着数百万人的生活质量。当前的治疗金标准——自体移植，无法恢复神经功能，且常常伴有不良影响。现有的替代干预措施仍无法确保完全的功能恢复。在本研究中，我们开发了一种由聚乳酸 - 乙醇酸共聚物（PLGA）和0.25%氧化石墨烯（GO）组成的3D打印神经引导导管（NGC），该导管可接种人脂肪来源间充质干细胞（MSCs），以开发一种更有效的PNI治疗方法。
我们在体外评估了材料降解、表面形貌和MSCs附着情况。对于体内分析，创建了一个10毫米长的坐骨神经缺损模型，并将大鼠随机分为4个治疗组：自体移植组、PLGA组、PLGA/GO组和接种1×10 MSCs的PLGA/GO组。在6个月的时间里：使用压力垫走道评估生物力学以确定功能修复情况；使用肾脏和肺组织的透射电子显微镜评估全身毒性；免疫组织化学评估局部不良反应、髓鞘和轴突修复情况；对腓肠肌外侧头、腓肠肌内侧头和比目鱼肌进行大体肌肉分析以评估肌肉再支配情况。
体外结果显示了预期的降解速率，添加GO表现出细胞相容性和良好的细胞附着性。体内结果显示生物相容性良好，氧化石墨烯纳米颗粒无移位。组织学显示有轴突和髓鞘修复的证据。生物力学和大体肌肉分析对于添加GO后的功能修复有相互矛盾的证据。添加MSCs未见差异。
我们新型的PLGA/GO NGC，无论有无MSCs，其结果均与当前金标准相当或更好，且手术使用方便。随着进一步研究以验证功能恢复情况，PLGA和GO的这种特定组合可能提供一种有效的仿生疗法来修复PNIs。
