Zolfagharzadeh Vahid, Ai Jafar, Soltani Hadi, Hassanzadeh Sajad, Khanmohammadi Mehdi
Chemical Engineering Department, Engineering Faculty, Ahar Branch, Islamic Azad University, Ahar, Iran.
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Biol Macromol. 2023 Jan 15;225:687-700. doi: 10.1016/j.ijbiomac.2022.11.133. Epub 2022 Nov 17.
We developed insulin loaded biomimetic microsphere by laccase-mediated crosslinking using a microfluidic device in the water-in-oil emulsion system as an injectable vehicle for the repair of sciatic tissue. Aqueous polymeric solution of phenol-substituted hyaluronic acid (HAPh) and collagen (ColPh) containing insulin and laccase flowed from the inner channel into oil flow within an outer channel which leads formation of hydrogel microsphere. The physical properties of prepared specimens including swelling rate, mechanical resistance and the prolonged release rate of microspheres proved applicability of fabricated vehicles for tissue engineering and drug delivery systems. The growth profile and behavior of cells in microspheres indicated cytocompatibility of the method and prepared vehicles for microtissue development. Histopathological examination revealed a significant increase in axonal regeneration, and remyelination process in injured sciatic nerve following treatment with HAPh/ColPh microspheres containing insulin compared to control groups. Also, the functional characteristic of sciatic tissue showed that the presence of biomimetic microsphere and insulin simultaneously had improved sciatic tissue functions including functional sciatic index (SFI) values, reaction to hot plate and muscle weight of rats. In summary, the results proved that composite biomimetic microspheres containing insulin effectively improved nerve regeneration in the rat model.
我们在油包水乳液体系中使用微流控装置，通过漆酶介导的交联反应制备了负载胰岛素的仿生微球，作为修复坐骨神经组织的可注射载体。含有胰岛素和漆酶的酚取代透明质酸（HAPh）和胶原蛋白（ColPh）的聚合物水溶液从内通道流入外通道内的油流中，从而形成水凝胶微球。所制备样品的物理性质，包括微球的溶胀率、机械抗性和缓释率，证明了所制备的载体在组织工程和药物递送系统中的适用性。微球中细胞的生长情况和行为表明了该方法以及所制备的用于微组织发育的载体的细胞相容性。组织病理学检查显示，与对照组相比，用含胰岛素的HAPh/ColPh微球治疗后，受损坐骨神经的轴突再生和髓鞘再生过程显著增加。此外，坐骨神经组织的功能特性表明，仿生微球和胰岛素同时存在可改善坐骨神经组织的功能，包括大鼠的功能坐骨指数（SFI）值、对热板的反应和肌肉重量。总之，结果证明含胰岛素的复合仿生微球能有效促进大鼠模型中的神经再生。
