Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.
- Article type
- Year
- Co-author
Open Access
Review
Issue
Open Access
Research Article
Issue
Random skin flap application is considerably limited by postoperative complications, particularly distal tissue ischemia and necrosis. Melatonin, a molecule with well-documented antioxidant and cytoprotective properties, has shown promise in protecting ischemic tissues. However, its specific role in regulating ferroptosis during ischemic flap injury, as well as its safety and efficacy in primate models (a key step for clinical translation), remains to be systematically validated. In this study, we aimed to promote angiogenesis within flap tissue through exogenous melatonin administration and to inhibit ferroptosis to mitigate ischemia–reperfusion injury, presenting a novel strategy for enhancing flap survival rates.
A random skin flap was constructed in C57BL/6 J mice. After melatonin treatment for seven days, the influence of melatonin on the levels of oxidative stress, iron accumulation, and mitochondrial morphology within the skin flap tissue was assessed. We used Transwell migration assays, tube formation assays, flow cytometry, and immunofluorescence staining to determine the effects of melatonin in vitro. The ferroptosis inducer erastin was used in combination with melatonin to treat random skin flap mice and tert-butyl hydroperoxide (TBHP)–induced cellular models, and the pathway through which melatonin counteracts iron mutations was explored. Lastly, we conducted experiments using nonhuman primate models and analyzed the protective effects of melatonin on ischemic flaps in macaques, highlighting its potential for clinical translation.
Melatonin ameliorated the survival area of ischemic flaps in mice, enhanced angiogenesis, reduced mitochondrial damage, and also suppressed lipid peroxidation and iron ion accumulation. Melatonin attenuated TBHP-induced cell death, lipid peroxidation, and mitochondrial damage in vitro. Further mechanistic studies revealed that melatonin inhibited ferroptosis, accompanied by nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), and increases the expression of downstream gene (effector) heme oxygenase-1 (HO-1). More importantly, experiments in macaques demonstrated that melatonin could enhance flap viability and angiogenesis, and exhibited a good safety profile.
Melatonin enhanced flap viability in mice and macaques by inhibiting ferroptosis, boosting angiogenesis, and attenuating oxidative stress injury.
Open Access
Review
Issue
Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit (NVU), pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury (SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics.
京公网安备11010802044758号