In recent decades, there have been tremendous improvements in burn care that have allowed patients to survive severe burn injuries that were once fatal. However, a major limitation of burn care currently is the development of hypertrophic scars in approximately 70% of patients. This significantly decreases the quality of life for patients due to the physical and psychosocial symptoms associated with scarring. Current approaches to manage scarring include surgical techniques and non-surgical methods such as laser therapy, steroid injections, and compression therapy. These treatments are limited in their effectiveness and regularly fail to manage symptoms. As a result, the development of novel treatments that aim to improve outcomes and quality of life is imperative. Drug delivery that targets the molecular cascades of wound healing to attenuate or prevent hypertrophic scarring is a promising approach that has therapeutic potential. In this review, we discuss current treatments for scar management after burn injury, and how drug delivery targeting molecular signaling can lead to new therapeutic strategies.

Background: Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. Methods: To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. Results: At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin's effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. Conclusion: In summary, metformin's various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia.

A boy aged 21 months who was being investigated for developmental delay and failure to thrive was found to have punctate epiphyseal calcification. He had no evidence of rhizomelic shortening of the limbs or cataracts. Investigation revealed defective plasmalogen synthesis due to isolated deficiency of dihydroxyacetonephosphate acyltransferase (DHAP-AT). The parents were consanguineous and a sister was similarly affected, suggesting autosomal recessive inheritance. Hitherto, recessively inherited isolated DHAP-AT deficiency has only been described in patients with a phenotype similar to that of rhizomelic chondrodysplasia punctata. This report indicates that the same biochemical disorder can be associated with a less severe phenotype.

BackgroundSevere burn results in a systemic response that leads to significant muscle wasting. It is believed that this rapid loss in muscle mass occurs due to increased protein degradation combined with reduced protein synthesis. Alterations in the microenvironment of muscle progenitor cells may partially account for this pathology. The aim of this study was to ascertain the response of muscle progenitor cells following thermal injury in mice and to enlighten the cellular cascades that contribute to the muscle wasting.MethodsC57BL/6 mice received a 20% total body surface area (TBSA) thermal injury. Gastrocnemius muscle was harvested at days 2, 7, and 14 following injury for protein and histological analysis.ResultsWe observed a decrease in myofiber cross-sectional area at 2 days post-burn. This muscle atrophy was compensated for by an increase in myofiber cross-sectional area at 7 and 14 days post-burn. Myeloperoxidase (MPO)-positive cells (neutrophils) increased significantly at 2 days. Moreover, through Western blot analysis of two key mediators of the proteolytic pathway, we show there is an increase in Murf1 and NF-κB 2 days post-burn. MPO-positive cells were also positive for NF-κB, suggesting that neutrophils attain NF-κB activity in the muscle. Unlike inflammatory and proteolytic pathways, the number of Pax7-positive muscle progenitor cells decreased significantly 2 days post-burn. This was followed by a recovery in the number of Pax7-positive cells at 7 and 14 days, suggesting proliferation of muscle progenitors that accompanied regrowth.ConclusionOur data show a biphasic response in the muscles of mice exposed to burn injury, with phenotypic characteristics of muscle atrophy at 2 days while compensation was observed later with a change in Pax7-positive muscle progenitor cells. Targeting muscle progenitors may be of therapeutic benefit in muscle wasting observed after burn injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0686-z) contains supplementary material, which is available to authorized users.