Diabetic wounds present a significant challenge in clinical treatment and are characterized by chronic inflammation, oxidative stress, impaired angiogenesis, peripheral neuropathy, and a heightened risk of infection during the healing process. By creating small channels in the surface of the skin, microneedle technology offers a minimally invasive and efficient approach for drug delivery and treatment. This article begins by outlining the biological foundation of normal skin wound healing and the unique pathophysiological mechanisms of diabetic wounds. It then delves into the various types, materials, and preparation processes of microneedles. The focus is on the application of multifunctional microneedles in diabetic wound treatment, highlighting their antibacterial, anti-inflammatory, immunomodulatory, antioxidant, angiogenic and neural repair properties. These multifunctional microneedles demonstrate synergistic therapeutic effects by directly influencing the wound microenvironment, ultimately accelerating the healing of diabetic wounds. The advancement of microneedle technology not only holds promise for enhancing the treatment outcomes of diabetic wounds but also offers new strategies for addressing other chronic wounds.

Chronic diabetic wounds affect the quality of life of patients, resulting in significant social and economic burdens on both individuals and the health care system. Although treatment methods for chronic diabetic wounds have been explored, there remains a lack of effective treatment strategies; therefore, alternative strategies must be explored. Recently, the abnormal expression of non-coding RNA in diabetic wounds has received widespread attention since it is an important factor in the development of diabetic wounds. This article reviews the regulatory role of three common non-coding RNAs (microRNA [miRNA], long non-coding RNA [lncRNA], and circular RNA [circRNA]) in diabetic wounds and discusses the diagnosis, treatment potential, and challenges of non-coding RNA in diabetic wounds. This article provides insights into new strategies for diabetic wound diagnosis and treatment at the genetic and molecular levels.

The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.

Background: Secondary lymphedema is a chronic, disabling disease affecting more than 50% of patients with cancer and lacking effective pharmacologic treatment even for early to middle disease stages. Metformin reportedly exerts anti-inflammatory and antifibrotic effects and is safe, with minimal side effects. The authors investigated the role of metformin in lymphedema mouse models and examined underlying molecular mechanisms. Methods: Male C57BL/6 mice (6 to 8 weeks old; n = 15/group) received metformin (300 mg/kg/day) by gavage on day 3 after lymphedema surgery; saline and sham groups were administered the same volume of saline. Hindlimb circumference and tail volume were monitored every 2 days. On day 28, samples were collected for histologic assessment, Western blotting, and reverse transcription quantitative polymerase chain reaction analysis of inflammation, fibrosis, and AMP-activated protein kinase (AMPK) expression. AMPK activity was assayed in patients with secondary lymphedema (International Society of Lymphology stage II) and controls following strict inclusion criteria. Results: Compared with the saline group, the metformin group exhibited hindlimb circumference and tail volume reduced by 469.70% and 305.18%, respectively, on day 28. Dermal thickness was reduced by 38.27% and 72.57% in the hindlimbs and tail, respectively. Metformin decreased CD4+ T-cell infiltration by 19.73%, and decreased expression levels of interleukin-4, interleukin-13, interleukin-17, and transforming growth factor–β1. In addition, it lowered collagen I deposition by 33.18%. Compared with the saline group, the number of lymphatic vessels increased by 229.96% in the metformin group. Both the saline group mice and patients with lymphedema showed reduced AMPK activity; metformin increased p-AMPK expression by 106.12%. Conclusion: Metformin alleviated inflammation and fibrosis and increased lymphangiogenesis in lymphedema mouse models by activating AMPK signaling. Clinical Relevance Statement: Metformin provides preliminary evidence as a potential therapeutic option for lymphedema.