Therapeutic Strategies to Reduce Burn Wound Conversion

Abstract

Burn wound conversion refers to the phenomenon whereby superficial burns that appear to retain the ability to spontaneously heal, convert later into deeper wounds in need of excision. While no current treatment can definitively stop burn wound conversion, attempts to slow tissue damage remain unsatisfactory, justifying the need for new therapeutic interventions. To attenuate burn wound conversion, various studies have targeted at least one of the molecular mechanisms underlying burn wound conversion, including ischemia, inflammation, apoptosis, autophagy, generation of reactive oxygen species, hypothermia, and wound rehydration. However, therapeutic strategies that can target various mechanisms involved in burn wound conversion are still lacking. This review highlights the pathophysiology of burn wound conversion and focuses on recent studies that have turned to the novel use of biologics such as mesenchymal stem cells, biomaterials, and immune regulators to mitigate wound conversion. Future research should investigate mechanistic pathways, side effects, safety, and efficacy of these different treatments before translation into clinical studies.

Autophagy is the key to making chronic wounds acute in skin wound healing

“…For example, at the inflammatory stage of thermal burn wound healing, autophagic activity influenced by different levels of cytokines (notably IL1, IL6, IL10, and IL18), TNF and IFNG/IFN-γ (interferon gamma) begins to increase after 24 h but it does not reach normal levels until up to 72 h after the burn injury occurs [ 31 ]. At this stage, autophagy acts as a molecular pro-survival mechanism – as demonstrated by increased levels of biomarkers of autophagic activity, namely MAP1LC3/LC3 (microtubule associated protein 1 light chain 3; specifically membrane-bound LC3-II) and BECN1 (beclin 1) – that protects cells against stress effects, and even cell necrosis, caused by strong pro-inflammatory cytokines and/or triggered by microbial load [ 31 , 32 ].…”

“…To once again look at the effects of autophagy in thermal burn wound healing, keratinocyte growth factor-controlled differentiation at the proliferative and remodeling stages of wound healing triggers LC3 expression and autophagy initiation via the phosphoinositide 3-kinase (PI3K)-AKT (AKT serine/threonine kinase)-MTOR (mechanistic target of rapamycin kinase) signaling pathway, lysosomal enzyme activation and downstream autophagic machinery – as Atg5 -deficient keratinocytes are unable to undergo differentiation [ 31 ]. Additionally, autophagy levels increase during heat-denatured endothelial cell recovery, depending on intracellular reactive oxygen species generation and overall oxidative stress as well as subsequent initiation of autophagy through AMP-activated protein kinase/AMPK and MTOR signaling pathways resulting in enhanced angiogenesis [ 31 , 32 ].…”

A single-center, open-labeled, randomized, 6-month, parallel-group study to assess the safety and efficacy of allogeneic cultured keratinocyte sheet transplantation for deep second-degree burn wounds: rationale and design of phase I/II clinical trial

“…Nowadays, thanks to the advancements in molecular and personalized medicine, the management of burn injuries entered a new era [ 18 ]. To date, many progressions have been conducted to ameliorate burn wounds, which facilitates different stages of wound healing including ischemic phase, inflammatory phase, or wound rehydration [ 19 ]. Regenerative medicine and stem cell-based treatments have had promising advancements in the management of different types of wounds through accelerating the healing process [ 20 ].…”

Tunable Sulfated Alginate-based Hydrogel Platform with enhanced anti-inflammatory and antioxidant capacity for promoting burn wound repair

“…The inflammatory storm that occurs during the initial phase of wound healing can exacerbate tissue damage and disrupt natural healing processes, including timely vascular formation and orderly collagen arrangement [4]. Consequently, deep second-degree burn wounds often necessitate surgical intervention, leading to considerable pain and added burden for the patient [4][5][6]. Given these circumstances, immunomodulatory hydrogels targeting M1 macrophages, ROS, and inflammatory chemokines emerge as potential novel therapeutic modalities for the treatment of deep second-degree burn wounds.…”