Hydrogel Microneedles for Chronic Wound Microenvironment Remodeling: From Drug Delivery to Intelligent Responsiveness

Abstract

The considerable strain that chronic wounds, including diabetic foot ulcers and pressure sores, place on healthcare systems worldwide is largely attributable to the intricate pathological microenvironment characteristic of these conditions, and conventional therapeutic approaches frequently fall short of desired outcomes, primarily because they cannot effectively disrupt biofilm barriers or adequately adapt to the dynamically changing pathological states involved. Hydrogel microneedles (HMNs) have by contrast emerged as a minimally invasive platform whose distinctive structural features and material properties enable both precise transdermal drug administration and active modulation of the wound microenvironment, and this dual capability is why HMNs are currently transforming chronic wound care by shifting the paradigm from passive occlusive dressings toward more proactive and targeted regenerative interventions. This review summarizes recent progress in HMN-based strategies for chronic wound healing and offers perspectives on future developments, beginning with an examination of fundamental design principles such as material choices, structural arrangements, and the various approaches developed to optimize performance metrics, then tracing the evolution of HMNs from simple drug carriers to intelligent multifunctional systems with special attention to their roles in breaking the pathological cycle through antibacterial effects, reactive oxygen species (ROS) scavenging, immune response modulation, and promotion of angiogenesis. Advances in stimuli-responsive systems that utilize endogenous signals including pH, enzymes, ROS, and glucose or external inputs like light and magnetic fields for on-demand release are also covered, as are combination platforms that integrate different therapeutic strategies for additive benefits. Clinical translation faces a number of challenges despite the considerable promise HMNs exhibit in theranostic applications, regenerative medicine integration, and customized fabrication, with obstacles remaining regarding scalable production that ensures consistent quality across batches, long-term biosafety verification, and unclear regulatory pathways; overcoming these hurdles will depend on sustained interdisciplinary efforts that address both scientific understanding and engineering practicality, and without such collaborative work the meaningful incorporation of HMNs into routine clinical management of chronic wounds along with the consequent availability of more effective, accurate, and intelligent treatment options could be difficult to achieve.