Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing

Abstract

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and peripheral vascular disease due to long-term continuous exposure to high glucose. Delayed wound healing in diabetes is one of the major complications of diabetes. Slow wound healing in diabetic patients is associated with high glucose toxicity. When the condition deteriorates, the patient needs to be amputated, which seriously affects the quality of life and even endangers the life of the patient. In general, the delayed healing of diabetes wound is due to the lack of chemokines, abnormal inflammatory response, lack of angiogenesis and epithelial formation, and fibroblast dysfunction. The incidence of several chronic debilitating conditions is increasing in patients with diabetes, such as chronic renal insufficiency, heart failure, and hepatic insufficiency. Fibrosis is an inappropriate deposition of extracellular matrix (ECM) proteins. It is common in diabetic patients causing organ dysfunction. The fibrotic mechanism of diabetic fibroblasts may involve direct activation of permanent fibroblasts. It may also involve the degeneration of fibers after hyperglycemia stimulates immune cells, vascular cells, or organ-specific parenchymal cells. Numerous studies confirm that fibroblasts play an essential role in treating diabetes and its complications. The primary function of fibroblasts in wound healing is to construct and reshape the ECM. Nowadays, with the widespread use of single-cell RNA sequencing (scRNA-seq), an increasing number of studies have found that fibroblasts have become the critical immune sentinel cells, which can detect not only the activation and regulation of immune response but also the molecular pattern related to the injury. By exploring the heterogeneity and functional changes of fibroblasts in diabetes, the manuscript discusses that fibroblasts may be used as immunomodulatory factors in refractory diabetic wound healing, providing new ideas for the treatment of refractory diabetic wound healing.

Local Application of Krill Oil Accelerates the Healing of Artificially Created Wounds in Diabetic Mice

“…Under the diabetic condition, the inflammation period is prolonged and sustained, delaying wound healing [ 23 ]. Compared with inflammation, fibrosis and neoangiogenesis occur at a relatively later stage [ 25 , 26 ], and are inhibited upon DM [ 26 ]. In the present study, DM was found to induce a prominent inflammatory state in D7 and to inhibit fibrosis and neoangiogenesis in D16 ( Figure 3 , Figure 5 , and Figure 7 ), confirming the temporal specificity of different pathophysiological processes in diabetic wound healing.…”

Recent Advances in Living Algae Seeding Wound Dressing: Focusing on Diabetic Chronic Wound Healing

“…Additionally, hyperglycemia inhibits cell migration and proliferation, resulting in vascular damage, hypoxia, abnormal accumulation of extracellular matrix (ECM), delayed re-epithelialization, and excessive scar formation (Figure 2). [3,26,27]…”

“…These ulcers not only cause significant physical and psychological pain to patients but also impose a DOI: 10.1002/adfm.202308387 substantial burden on the economy and society as a whole. [1][2][3] Under typical conditions, the process of wound closure is an intricate and meticulously orchestrated physiological phenomenon comprising four interrelated and sequential stages: hemostasis, inflammation, proliferation (re-epithelialization), and remodeling (scar maturation). These stages overlap and work in harmony to ensure proper healing of the wound.…”

Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing

“…Perpetuated inflammatory states induced by increased mast cell degranulation[ 33 ], excessive extracellular traps produced by neutrophils[ 34 ], dysregulated and persistent M1 (pro-inflammatory) macrophage polarization[ 35 ], pro-inflammatory factors (IL-1β, TNF-α, and IL-6) overexpression, and anti-inflammatory factors (IL-10 and TGF-β) deficiency finally hinder wound healing[ 7 ]. The proliferative phase of diabetic wound healing is characterized by disturbed physiological functions of keratinocytes[ 36 ], fibroblasts[ 37 ], and endothelial cells[ 38 ], then the impaired re-epithelialization, granulation tissue formation, matrix deposition, and angiogenesis affect wound healing. Various factors also affect the function and activity of these cells during this phase, including decreased chemokines with pro-angiogenesis produced by macrophages, hemoglobin glycation, vascular stenosis, increased oxygen consumption affecting oxygen-dependent cellular behaviors, and impaired nerve fiber regeneration[ 7 , 31 , 39 , 40 ].…”