Kopach Olga, Pavlov Anton M, Sindeeva Olga A, Sukhorukov Gleb B, Rusakov Dmitri A
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
Pharmaceutics. 2020 Dec 25;13(1):25. doi: 10.3390/pharmaceutics13010025.
Neurological disorders and traumas often involve loss of specific neuronal connections, which would require intervention with high spatial precision. We have previously demonstrated the biocompatibility and therapeutic potential of the layer-by-layer (LbL)-fabricated microcapsules aimed at the localized delivery of specific channel blockers to peripheral nerves. Here, we explore the potential of LbL-microcapsules to enable site-specific, directional action of neurotrophins to stimulate neuronal morphogenesis and synaptic circuit formation. We find that nanoengineered biodegradable microcapsules loaded with nerve growth factor (NGF) can guide the morphological development of hippocampal neurons in vitro. The presence of NGF-loaded microcapsules or their clusters increases the neurite outgrowth rate while boosting neurite branching. Microcapsule clusters appear to guide the trajectory of developing individual axons leading to the formation of functional synapses. Our observations highlight the potential of NGF-loaded, biodegradable LbL-microcapsules to help guide axonal development and possibly circuit regeneration in neuropathology.
神经疾病和创伤常常涉及特定神经元连接的丧失，这就需要进行具有高空间精度的干预。我们之前已经证明了层层组装（LbL）制备的微胶囊的生物相容性和治疗潜力，其旨在将特定的通道阻滞剂局部递送至外周神经。在此，我们探索LbL微胶囊实现神经营养因子的位点特异性、定向作用以刺激神经元形态发生和突触回路形成的潜力。我们发现，装载有神经生长因子（NGF）的纳米工程可生物降解微胶囊能够在体外引导海马神经元的形态发育。装载有NGF的微胶囊或其簇的存在提高了神经突生长速率，同时增加了神经突分支。微胶囊簇似乎能够引导发育中的单个轴突的轨迹，从而导致功能性突触的形成。我们的观察结果突出了装载有NGF的、可生物降解的LbL微胶囊在神经病理学中帮助引导轴突发育以及可能的回路再生的潜力。
