Berlanga-Acosta, J.; Garcia-Ojalvo, A.; Guillen-Nieto, G.; Ayala-Avila, M. Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections. Int. J. Mol. Sci.2023, 24, 10170.
Berlanga-Acosta, J.; Garcia-Ojalvo, A.; Guillen-Nieto, G.; Ayala-Avila, M. Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections. Int. J. Mol. Sci. 2023, 24, 10170.
Berlanga-Acosta, J.; Garcia-Ojalvo, A.; Guillen-Nieto, G.; Ayala-Avila, M. Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections. Int. J. Mol. Sci.2023, 24, 10170.
Berlanga-Acosta, J.; Garcia-Ojalvo, A.; Guillen-Nieto, G.; Ayala-Avila, M. Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections. Int. J. Mol. Sci. 2023, 24, 10170.
Abstract
An impaired healing response underlies diabetic foot wounds chronicity, frequently translating in amputation, disability, and early mortality. In addition, diabetics frequently suffer of the underappreciated episode of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high; so that the ulcer is considered in “remission” and not healed for the time it remains epithelialized. Recurrence may result from the conspiracy of behavioral and biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, the role of endogenous biological signalers that prime the residual scar tissue to recurrence has remained elusive. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts, and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblasts-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers, induce the onset of “at-risk phenotypes” as premature skin cells aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cells demise. Unfortunately, post epithelialization recurrence rates data are missing in clinical studies of accepted ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.
Medicine and Pharmacology, Endocrinology and Metabolism
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