Hydrogel microneedles functioning in pathological surroundings: where soft materials overcome hard scars

Pathological scarring is a manifestation of abnormal skin wound healing characterized by fibrosis, resulting from excessive fibroblast activation and abnormal deposition of the extracellular matrix, Currently, the main treatment options, such as corticosteroid injections or ointments, cryotherapy, laser therapy and radiation therapy, face some challenges in their application. For example, long-term corticosteroid injections can lead to side effects of skin atrophy and telangiectasia; topical ointments have limited penetration. Cryotherapy lacks precision and damages the surrounding skin, leading to pigmentation abnormalities. Laser treatment requires multiple sessions with long treatment period and costly fee. Radiation therapy has a very limited scope of application, and even low-dose radiation can still damage surrounding tissues. Hydrogels microneedles (HMNs) represent a novel transdermal drug delivery platform. The microneedle structure enables them to penetrate the stratum corneum, facilitating precise drug delivery, and the materials used to prepare HMNs exhibit excellent biocompatibility and biodegradability, thereby reducing the risk of skin irritation and allergic reactions. Furthermore, stimuli-responsive hydrogels have also demonstrated significant potential and distinct advantages in the field of scar treatment. However, a comprehensive report on HMNs for scar treatment are rarely conducted. This review provides a systematic overview of HMNs technology for pathological scar treatment, summarizing recent research advances in this area. Firstly, the design and fabrication of HMNs is discussed about material preparation methods and numerous smart responsive HMNs are detailedly demonstrated. Secondly, various action mechanisms involved in scar treatment are outlined. Subsequently, the current status of clinical application research in scar treatment are summarized. Finally, the current bottlenecks in HMNs technology regarding drug loading capacity and penetration depth are highlighted, and future directions such as smart responsiveness, personalised therapy and the integration with artificial intelligence (AI) to facilitate the clinical translation of HMNs technology are outlined and envisaged.