多巴胺能轴突在透明质酸水凝胶包被内的延伸,以恢复黑质纹状体通路

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL Advanced Healthcare Materials Pub Date : 2024-11-04 DOI:10.1002/adhm.202402997
Wisberty J Gordián-Vélez, Kevin D Browne, Jonathan H Galarraga, Dimple Chouhan, John E Duda, Rodrigo A España, H Isaac Chen, Jason A Burdick, D Kacy Cullen
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引用次数: 0

摘要

帕金森病的特点是,构成黑质通路的多巴胺能神经元及其长轴突变性后,纹状体中的多巴胺不足,从而导致运动障碍。为了解决这个问题,我们开发了一种组织工程化黑质通路(TE-NSP),其特点是管状水凝胶以胶原蛋白/层粘连蛋白为核心,包裹聚集的多巴胺能神经元及其轴突束。这种工程微组织可以植入以替代神经元和轴突,忠实于失去的通路,因此可以根据宿主电路的反馈提供多巴胺。TE-NSP 传统上是用琼脂糖制造的,而这里使用的透明质酸(HA)水凝胶具有更强的生物活性,同时扩大了对物理和生化特性的控制。利用大鼠腹侧中脑神经元发现,相对于琼脂糖,透明质酸水凝胶(HA)改善了 TE-NSP 的神经元生长,但在电诱发多巴胺释放方面没有差异。移植时,与琼脂糖相比,HA 水凝胶减少了宿主神经元的平均损失和植入物周围的炎症,TE-NSP 神经元和轴突束存活至少 2 周,在结构上模拟了丢失的通路。这项研究代表了 HA 水凝胶在神经再生医学中的创新应用,并使未来的研究能够扩大 TE-NSP 的控制和功能。
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Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.

Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry. While TE-NSPs have traditionally been fabricated with agarose, here a hyaluronic acid (HA) hydrogel is utilized to have a more bioactive encasement while expanding control over physical and biochemical properties. Using rat ventral midbrain neurons, it is found that TE-NSPs exhibited improved neurite growth with HA relative to agarose, with no differences in electrically-evoked dopamine release. When transplanted, HA hydrogels reduced average host neuron loss and inflammation around the implant compared to agarose, and TE-NSP neurons and axonal tracts survived for at least 2 weeks to structurally emulate the lost pathway. This study represents an innovative use of HA hydrogels for neuroregenerative medicine and enables future studies expanding the control and functionality of TE-NSPs.

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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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