An ECM-Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions
An ECM-Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions
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用于治疗脑损伤的模拟 ECM、可注射、粘弹性水凝胶
DOI：
10.1002/adhm.202201594
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发表时间：
2022-12-04
影响因子：
10
通讯作者：
Xu, Feng
中科院分区：
文献类型：
--
作者：
Hu, Yan;Jia, Yuanbo;Xu, Feng
脑损伤可由创伤性脑损伤、感染和开颅术引起。尽管可注射水凝胶显示出促进病变愈合和周围组织健康的前景，但使细胞向内生长和恢复神经组织仍然具有挑战性。据推测，这些挑战部分来自于水凝胶和脑实质之间的组成、刚度和粘弹性的不匹配，并且通过开发和评估自愈合水凝胶来测试该假设，该自愈合水凝胶不仅模拟了组成，而且模拟了天然脑实质的刚度和粘弹性。该水凝胶通过苯基硼酸接枝的透明质酸（HA-PBA）和多巴胺接枝的明胶（Gel-Dopa）之间的动态硼酸酯键交联。这种HA-PBA/Gel-Dopa水凝胶可以以剪切稀化的方式注射到病变腔中，具有快速止血、高组织粘附和有效的自我愈合。在脑损伤的体内小鼠模型中，发现多功能可注射水凝胶支持神经细胞浸润，减少星形胶质细胞增生和神经胶质瘢痕，并闭合损伤。结果表明，细胞外基质模仿粘弹性在脑损伤愈合中的作用，并激励在更大的动物中进行更多的实验，因为该技术在人类中的潜在应用。
Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self-healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma. The hydrogel is crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion, and efficient self-healing. In an in vivo mouse model of brain lesions, the multi-functional injectable hydrogel is found to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for extracellular matrix-mimicking viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses toward potential application in humans.