Current Diabetes Reviews - Current Issue

Wound healing is a complex process involving various cellular and molecular events aimed at restoring tissue integrity. Growth factors play a pivotal role in orchestrating these events by regulating cell migration, proliferation, differentiation, and extracellular matrix synthesis. Several growth factors have been identified as crucial mediators of wound healing, including PDGF, TGF-β, VEGF, FGF, and EGF. PDGF is released by platelets upon injury and stimulates the migration and proliferation of fibroblasts and smooth muscle cells, promoting the formation of granulation tissue. TGF-β regulates various aspects of wound healing, including inflammation, collagen deposition, and tissue remodeling. VEGF promotes angiogenesis, facilitating the formation of new blood vessels to supply oxygen and nutrients to the healing tissue. FGF stimulates fibroblast proliferation and angiogenesis, contributing to tissue regeneration. EGF promotes the migration and proliferation of epithelial cells, aiding in the re-epithelialization of the wound. These growth factors act in a coordinated manner to promote each phase of wound healing, including hemostasis, inflammation, proliferation, and remodeling. Dysregulation of growth factor expression or signaling can impair the healing process, leading to chronic wounds or excessive scar formation. Understanding the roles of growth factors in wound healing has led to the development of therapeutic strategies aimed at enhancing wound repair.

Diabetic Foot Ulcer (DFU) is a major complication of diabetes that mostly affects the lower extremities, with a high incidence and recurrence rate in approximately 15% of patients with diabetes. The complexity of diabetic wounds poses a substantial challenge for clinical recovery, underscoring the need to investigate novel therapeutic approaches. Medicinal plants have been used to treat ulcers for centuries. Recently, there has been a growing focus on the development of topical preparations derived from medicinal plants that target macrophages as an adjuvant therapy for DFU. Macrophages have been identified as crucial factors in the DFU healing process. This review aims to introduce the latest evidence and insights into the role of medicinal plants in promoting DFU recovery by targeting macrophages. The molecular mechanisms underlying the preventive effects of medicinal plants on DFU primarily involve promoting M2 polarization of macrophages, inhibition of M1 polarization, and regulation of macrophage function. This review highlights the substantial potential of advancing the field of DFU management by medicinal plants and lays the groundwork for novel therapeutic interventions.

Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca²⁺ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen-activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

Wound healing is a complex, tightly regulated biological process essential for restoring the integrity and functionality of damaged skin. Chronic wounds, affecting approximately 6.5 million individuals globally and 1.5% of the Indian population, pose significant healthcare challenges due to their prolonged and intricate healing processes. This review highlights the mechanisms and stages of wound healing—hemostasis, inflammation, proliferation, and maturation—emphasizing the bidirectional influence of internal and external factors on wound progression. Despite advancements in wound management, current therapeutic options, including skin grafts, growth factors, and cell-based therapies, often remain inadequate for diverse wound types. Emerging technologies, such as nanofibers, stem cell therapy, 3D bioprinting, fluorescence imaging, and bacteria-killing laser therapy, offer promising solutions by enhancing therapeutic outcomes and minimizing side effects. This review also explores the roles of nutrition, physical therapy, and traditional medicine in promoting effective wound care. By integrating novel technologies with established therapeutic strategies, this work provides a comprehensive overview of advanced wound healing modalities, their mechanisms, advantages, and limitations. The review concludes with a perspective on future research directions aimed at overcoming current challenges in chronic wound management and optimizing patient outcomes.

Diabetic-related complications, such as delayed and incomplete wound healing, are an increasing concern in the realm of public health. Ferroptosis represents an innovative variant of cellular demise. Ferroptosis is currently thought to be an essential factor in the process of diabetic wound recovery. This article, therefore, examines the novel function and mechanism of ferroptosis in the repair of diabetic wounds. Diabetic hyperglycemia can induce a healing process that disrupts the function and activity of cells, thereby impeding the repair of diabetic wounds. Ferroptosis may be accelerated in diabetic lesions due to protracted low-level inflammation and oxidative stress induced by elevated glucose, according to the available evidence. As a result, the buildup of ferroptosis impedes cellular migration and proliferation, amplifies oxidative stress and the inflammatory response, and ultimately interferes with the wound-healing process. By regulating the expression of factors linked to iron mortality, this substance expedites wound healing and fosters angiogenesis in diabetic rodents. Moreover, new perspectives on the difficulties and outlooks related to ferroptosis in the context of diabetic wound healing are provided, thereby contributing to the progression of understanding in this field.

Diabetic wounds are a class of chronic wounds that exhibit significant healing abnormalities due to dysregulated cytokines, growth factors, and unique cellular expressions, currently affecting an estimated 9.1-26.1 million people per year globally. Matrix metalloproteinases (MMPs), angiogenic factors, and inflammatory mediators remain the key determinants for managing diabetic wounds. Vascular endothelial growth factor (VEGF) is one of the most prominent types of growth factors induced during angiogenesis in general and cell proliferation pathways. Chronic hyperglycemia, neuropathy, and inflammation associated with diabetes disorders affect cellular responses, blood circulation, and immunological systems impair normal wound healing. This reduced effectiveness of current management strategies is reflected in the high number of delayed wounds among diabetic patients due to escalated oxidative stress and impaired signaling pathways, which prevent healing, calling for new therapies. MMPs are essential for tissue remodeling, but excess levels of MMPs predispose tissues to matrix degradation and interruption in cell signaling leading thereby prolonging inflammation seen in diabetic wounds. Efficient wound healing requires a balanced relationship regarding matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). New regenerative solutions, such as stem cells, platelet-rich plasma (PRP), gene therapies, and MMP inhibitors that can re-establish angiogenesis; decrease inflammation; and stimulate growth factor signaling, suggest promising strategies for improved diabetic wound healing. Hyperbaric oxygen therapy allows tissue regeneration and reduces the area of ulceration, bringing other benefits. In the future, therapeutics should focus on multifunctional and responsive strategies that include anti-inflammatory agents, cytokine modulators, and stem cell treatments that exhibit superior efficacy in comparison to conventional therapies when assessed clinically. Novel advanced combination strategies represent a realistic route to targeted therapies that meet clinical needs and have the potential capability for utilizing mechanistic insights, both creative in their implementation of recently developed techniques as well as applied on a broader scale through the evidence-based management across diabetic wounds offering better outcomes and quality of life amongst increasing diabetic commonalities.

Diabetic wounds constitute a significant global health challenge, affecting millions of individuals worldwide and imposing a substantial burden on healthcare systems. This review explores the complex pathophysiology of diabetic wound healing and discusses innovative interventions aimed at addressing this critical clinical problem. The impaired healing process in diabetic wounds is characterized by a multitude of interrelated factors, including cellular dysfunction, altered inflammatory responses, oxidative stress, the formation of advanced glycation end-products, and neurovascular abnormalities. Fibroblasts, keratinocytes, and endothelial cells demonstrate diminished proliferation and migration capabilities, while immune cells exhibit dysregulated responses, which contribute to a persistent inflammatory state. Complications associated with diabetes, such as neuropathy and vascular insufficiency, further exacerbate the wound healing process. Recent advancements in wound care strategies have opened new avenues for enhancing diabetic wound healing. These advancements encompass the development of advanced dressings and biomaterials, growth factor therapies, cell-based interventions, and gene therapy approaches. The integration of diverse treatment modalities, coupled with the management of systemic metabolic abnormalities, offers significant promise for improving outcomes in diabetic wound care. Future research should focus on optimizing combination therapies, developing personalized treatment algorithms, and conducting large-scale clinical trials to establish the most effective and safest interventions for diabetic wound healing.