Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes

Abstract

BackgroundImpaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes.Purpose of reviewAlthough many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.Recent findingsAlthough complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.SummaryThe adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.

Efficient healing of diabetic wounds by MSC-EV-7A composite hydrogel via suppression of inflammation and enhancement of angiogenesis

“…It is well-known that diabetic wounds exhibit a significantly delayed and refractory wound healing process, possibly due to the presence of chronic inflammation. 39,40 In contrast, the combination treatment group showed almost complete wound closure, confirming the importance of the enhanced anti-inflammation activity resulting from the incorporation of MSC-EVs and 7A in the hydrogel. This can be an important mechanism for the promotion of diabetic wound healing by such a combination therapy.…”

Investigating Inflammatory Markers in Wound Healing: Understanding Implications and Identifying Artifacts

“…It stimulates the production of collagen, fibronectin, and other matrix components essential for tissue repair, providing structural support and playing a significant role in the wound remodeling stage . Additionally, TGF-β activates myofibroblasts, leading to wound contraction, an essential step in the wound healing process . However, the dysregulation of TGF-β signaling can lead to the development of chronic wounds and impaired wound healing.…”

“…Inflammation starts the healing process in the early stages of wound healing. Immune cells (such as neutrophils and macrophages M1 phenotype) and pro-inflammatory cytokines are essential for clearing the wound area and attracting immune cells (such as macrophages M2 phenotype and T lymphocytes), and growth factors for tissue repair processes like angiogenesis, collagen synthesis, and re-epithelialization. − Efficient wound healing requires prompt inflammatory resolution. As wound healing progresses into the proliferative and remodeling phases, anti-inflammatory mediators aid in lowering the inflammatory response (Figure A,B).…”

“…52 Additionally, TGF-β activates myofibroblasts, leading to wound contraction, an essential step in the wound healing process. 53 However, the dysregulation of TGF-β signaling can lead to the development of chronic wounds and impaired wound healing. In chronic wounds, deficiencies or imbalances in TGF-β signaling may result in delayed healing and impaired tissue repair.…”

Investigating the Potential Impact of Air Pollution on Alzheimer’s Disease and the Utility of Multidimensional Imaging for Early Detection

“…It is also evidenced that, owing to the differences in men’s and women’s neural structures, women may be more at risk than men for decreased cognition linked to increased exposure to PM10 and PM2.5 . Generally, PM2.5 is associated with amyloid-β (Aβ) and α-synuclein aggregation , due to neuroinflammatory signals and oxidative stress including iNos and TNF- α, which ultimately disrupts lipid peroxidase and GFAP levels leading to the destruction of hippocampal cells (Figure ). Oxidative stress also leads to peripheral systemic inflammation-related neuronal injury via olfactory neurons, including oxidative stress-associated neurotoxicity and metabolic dysfunction …”