Advances and challenges in developing smart, multifunctional microneedles for biomedical applications

Abstract

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 singlemolecule sensing or delivery. Subsequently, we expand our insight into advanced MN systems with multiple competencies, such as body fluid extraction, biosensing,

Transdermal Drug Delivery System: Current Status and Clinical Application of Microneedles

“…Simultaneously, there is a research on multifunctional integrated intelligence, which is also a future development trend of microneedles in the medical field. Multifunctional intelligent integration refers to integrating intelligent technology with microneedle technology to achieve more functions and automation control in medical applications. These intelligent technologies can include sensors, microprocessors, wireless communication, and more, often involving multiple disciplines. − By integrating these technologies from various disciplines, it is possible to achieve automated operation, real-time monitoring, and remote control of microneedles, thereby improving the efficiency and accuracy of microneedle applications and expanding their medical applications. , However, the current research on the multifunctional integrated intelligence of microneedles is still in its early stages and generally focuses on combining sensor monitoring and drug delivery. Therefore, it can only achieve relatively simple environmental stimulus responses and basic indicator detection, and it cannot effectively respond to complex clinical environmental factors, thus having certain limitations.…”

“…99−101 By integrating these technologies from various disciplines, it is possible to achieve automated operation, realtime monitoring, and remote control of microneedles, thereby improving the efficiency and accuracy of microneedle applications and expanding their medical applications. 36,102 However, the current research on the multifunctional integrated intelligence of microneedles is still in its early stages and generally focuses on combining sensor monitoring and drug delivery. Therefore, it can only achieve relatively simple environmental stimulus responses and basic indicator detection, and it cannot effectively respond to complex clinical environmental factors, thus having certain limitations.…”

“…Microneedle drug delivery systems are the one of the advanced TDDS and currently a major research focus . The microneedle is classified into five categories based on the mode of transdermal administration, which is the most traditional classification: solid microneedle, coated microneedle, hollow microneedle, dissolvable microneedle, and hydrogel microneedle − (Figure A, Table ). They have been used extensively in various clinical research areas in recent years. − In the Supporting Information document (Supporting Information: Transdermal administration classification of microneedles), we have provided a detailed introduction to these traditional types of microneedles.…”

Functional Microneedle Patch for Wound Healing and Biological Diagnosis and Treatment

“…[81] Intelligent biomaterials can be relied upon to achieve the release of drugs in a stimulusresponsive manner when exposed to some external stimuli, such as pH and temperature. [82] Stimulus-responsive hydrogels are a good strategy for achieving controlled drug release and have great potentials in the treatment of chronic wound. Chi et al [83] developed a multifunctional wound healing patch with vascular endothelial growth factor (VEGF), which combined an intelligent temperature-sensitive hydrogel with a MN array (Figure 6B).…”

“…[ 81 ] Intelligent biomaterials can be relied upon to achieve the release of drugs in a stimulus‐responsive manner when exposed to some external stimuli, such as pH and temperature. [ 82 ] Stimulus‐responsive hydrogels are a good strategy for achieving controlled drug release and have great potentials in the treatment of chronic wound. Chi et al.…”