The human brain has unique features that are difficult to study in animal models, including the mechanisms underlying neurodevelopmental and psychiatric disorders. Despite recent advances in human primary brain tissue culture systems, the use of these models to elucidate cellular disease mechanisms remains limited. A major reason for this is the lack of tools available to precisely manipulate a specific area of the tissue in a reproducible manner. Here we report an easy-to-use tool for site-specific manipulation of human brain tissue in culture. We show that line-shaped cryogel scaffolds synthesized with precise microscale dimensions allow the targeted delivery of a reagent to a specific region of human brain tissue in culture. 3-sulfopropyl acrylate (SPA) was incorporated into the cryogel network to yield a negative surface charge for the reversible binding of molecular cargo. The fluorescent dyes BODIPY and DiI were used as model cargos to show that placement of dye loaded scaffolds onto brain tissue in culture resulted in controlled delivery without a burst release, and labelling of specific regions without tissue damage. We further show that cryogels can deliver tetrodotoxin to tissue, inhibiting neuronal function in a reversible manner. The robust nature and precise dimensions of the cryogel resulted in a user-friendly and reproducible tool to manipulate primary human tissue cultures. These easy-to-use cryogels offer an innovate approach for more complex manipulations of ex-vivo tissue.

人脑具有在动物模型中难以研究的独特特征，包括神经发育和精神疾病的潜在机制。尽管在人类主要脑组织培养系统方面有最新进展，但是使用这些模型阐明细胞疾病的机制仍然受到限制。造成这种情况的主要原因是缺乏可用的工具以可再现的方式精确地操纵组织的特定区域。在这里，我们报告了一种易于使用的工具，用于在培养中对人脑组织进行特定位置的处理。我们显示，以精确的微尺度尺寸合成的线形冷冻凝胶支架可将试剂定向递送至培养中的人脑组织的特定区域。将丙烯酸3-磺基丙酯（SPA）掺入冷冻凝胶网络中，以产生用于分子货物可逆结合的负表面电荷。荧光染料BODIPY和DiI将其用作模型货物，以表明将负载染料的支架放置在培养的脑组织上可实现受控递送而不会突然释放，并标记特定区域而不会损坏组织。我们进一步表明，冷冻凝胶可以将河豚毒素递送至组织，以可逆的方式抑制神经元功能。冷冻凝胶的坚固特性和精确尺寸导致了一种用户友好且可重现的工具，可以操纵原始人类组织培养物。这些易于使用的冷冻凝胶为活体外组织的更复杂操作提供了创新的方法。