Wound healing is vital for patients with complex wounds
including
burns. While the gold standard of skin transplantation ensures a surgical
treatment to heal wounds, it has its limitations, for example, insufficient
donor sites for patients with large burn wounds and creation of wounds
and pain when harvesting the donor skin. Therefore, tissue-engineered
skin is of paramount importance. The aim of this study is to investigate
and characterize an elastomeric acellular scaffold that would demonstrate
the ability to promote skin regeneration. A hybrid gelatin-based electrospun
scaffold is fabricated via the use of biodegradable polycarbonate
polyurethane (PU). It is hypothesized that the addition of PU would
enable a tailored degradation rate and an enhanced mechanical strength
of electrospun gelatin. Introducing 20% PU to gelatin scaffolds (Gel80–PU20)
results in a significant increase in the degradation resistance, yield
strength, and elongation of these scaffolds without altering the cell
viability. In vivo studies using a mouse excisional wound biopsy grafted
with the scaffolds reveals that the Gel80–PU20 scaffold enables
greater cell infiltration than clinically established matrices, for
example, Integra (dermal regeneration matrix, DRM), a benchmark scaffold.
Immunostaining shows fewer macrophages and myofibroblastic cells on
the Gel80–PU20 scaffold when compared with the DRM. The findings
show that electrospun Gel80–PU20 scaffolds hold potential for
generating tissue substitutes and overcoming some limitations of conventional
wound care matrices.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.