关键词: PI3K/AKT PLCL/SF/NGF@TA‐PPy‐RGD conductive hydrogel nerve conduit sciatic nerve defects

Mesh : Animals Nerve Regeneration / drug effects Rats Proto-Oncogene Proteins c-akt / metabolism Phosphatidylinositol 3-Kinases / metabolism Signal Transduction / drug effects PC12 Cells Sciatic Nerve / drug effects injuries Oligopeptides / pharmacology chemistry Hydrogels / chemistry Nerve Growth Factor / pharmacology metabolism Rats, Sprague-Dawley Male Cell Proliferation / drug effects Apoptosis / drug effects Tissue Scaffolds / chemistry Tissue Engineering / methods Polymers / chemistry

来  源:   DOI:10.1111/jcmm.18544   PDF(Pubmed)

Abstract:
Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.
摘要:
周围神经缺损是由外伤或其他疾病引起的临床常见病,常导致患者感觉和运动功能的丧失。自体神经移植一直是修复周围神经缺损的金标准,但由于供体组织不足,其临床应用受到限制。近年来,应用组织工程方法合成神经导管治疗周围神经缺损已成为当前的研究热点。这项研究介绍了一种使用组织工程PLCL/SF/NGF@TA-PPy-RGD导管治疗周围神经缺损的新方法。通过将电纺PLCL/SF与负载NGF的导电TA-PPy-RGD凝胶组合来制造导管。凝胶,由RGD修饰的单宁酸(TA)和聚吡咯(PPy)合成,为神经细胞提供生长锚点。体外实验结果表明,该杂交导管能增强PC12细胞的增殖,迁移,并减少氧化应激下的细胞凋亡。此外,导管激活PC12细胞中的PI3K/AKT信号通路。在大鼠坐骨神经缺损模型中,PLCL/SF/NGF@TA-PPy-RGD导管显著改善了运动功能,腓肠肌功能,和髓鞘轴突厚度,相当于自体神经移植。它还促进神经缺损周围的血管生成。这项研究表明,PLCL/SF/NGF@TA-PPy-RGD导管为神经再生提供了有利的环境,为周围神经缺损的治疗提供了新的策略,本研究为周围神经缺损的研究和治疗提供了理论依据和新策略。
公众号