Microneedles (MNs) have been developed as minimally invasive tools for diagnostic and therapeutic applications. However, in recent years, there has been an increasing interest in developing smart multifunctional MN devices to provide automated and closed-loop systems for body fluid extraction, biosensing, and drug delivery in a stimuli-responsive manner. Although this technology is still in its infancy and far from being translated into the clinic, preclinical trials have shown some promise for the broad applications of multifunctional MN devices. The main challenge facing the fabrication of smart MN patches is the integration of multiple modules, such as drug carriers, highly sensitive biosensors, and data analyzers in one miniaturized MN device. Researchers have shown the feasibility of creating smart MNs by integrating stimuli-responsive biomaterials and advanced microscale technologies, such as microsensors and microfluidic systems, to precisely control the transportation of biofluids and drugs throughout the system. These multifunctional MN devices can be envisioned in two distinct strategies. The first type includes individual drug delivery and biosensing MN units with a microfluidic system and a digital analyzer responsible for fluid transportation and communication between these two modules. The second type relies on smart biomaterials that can function as drug deliverers and biosensors by releasing drugs in a stimuli-responsive manner. These smart biomaterials can undergo structural changes when exposed to external stimuli, such as pH and ionic changes, mimicking the biological systems. Studies have demonstrated a high potential of hydrogel-based MN devices for a wide variety of biomedical applications, such as drug and cell delivery, as well as interstitial fluid extraction. Biodegradable hydrogels have also been advantageous for fabricating multifunctional MNs due to their high loading capacity and biocompatibility with the drug of choice. Here, we first review a set of MN devices that can be employed either for biosensing or delivery of multiple target molecules and compare them to the conventional and more simple systems, which are mainly designed for single-molecule sensing or delivery. Subsequently, we expand our insight into advanced MN systems with multiple competencies, such as body fluid extraction, biosensing, and drug delivery at the point of care. The improvement of biomaterials knowledge and biofabrication techniques will allow us to efficiently tune the next generation of smart MNs and provide a realistic platform for more effective personalized therapeutics.

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开发用于生物医学应用的智能多功能微针的进展和挑战

微针 (MN) 已被开发为用于诊断和治疗应用的微创工具。然而，近年来，人们越来越关注开发智能多功能 MN 设备，以便以刺激响应的方式为体液提取、生物传感和药物输送提供自动化和闭环系统。尽管这项技术仍处于起步阶段，远未转化为临床，但临床前试验已显示出多功能 MN 设备广泛应用的一些前景。制造智能 MN 贴片面临的主要挑战是在一个小型化 MN 设备中集成多个模块，例如药物载体、高灵敏度生物传感器和数据分析仪。研究人员已经展示了通过整合刺激响应生物材料和先进的微型技术（如微传感器和微流体系统）来精确控制整个系统中生物流体和药物的运输来创建智能 MN 的可行性。这些多功能 MN 设备可以设想为两种不同的策略。第一种类型包括单独的药物输送和生物传感 MN 单元，具有微流体系统和负责这两个模块之间的流体传输和通信的数字分析仪。第二种依赖于智能生物材料，可以通过以刺激响应的方式释放药物来充当药物输送器和生物传感器。这些智能生物材料在暴露于外部刺激时会发生结构变化，例如 pH 值和离子变化，模仿生物系统。研究表明，基于水凝胶的 MN 装置在各种生物医学应用中具有很高的潜力，例如药物和细胞递送以及间质液提取。可生物降解的水凝胶也有利于制造多功能 MN，因为它们具有高负载能力和与所选药物的生物相容性。在这里，我们首先回顾了一组可用于生物传感或传递多个目标分子的 MN 设备，并将它们与主要用于单分子传感或传递的传统和更简单的系统进行比较。随后，我们将洞察力扩展到具有多种能力的先进 MN 系统，例如体液提取、生物传感和护理点的药物输送。