Low-protein diet accelerates wound healing in mice post-acute injury.

BACKGROUND: Wound healing processes are influenced by macronutrient intake (protein, carbohydrate and fat). The most favourable diet for cutaneous wound healing is not known, although high-protein diets are currently favoured clinically. This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework, a nutrient modelling method, capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake. METHODS: Two adjacent and identical full-thickness skin excisions (1 cm2) were surgically created on the dorsal area of male C57BL/6 mice. Mice were then allocated to one of 12 high-energy diets that varied in protein, carbohydrate and fat content. In select diets, wound healing processes, cytokine expression, energy expenditure, body composition, muscle and fat reserves were assessed. RESULTS: Using the Geometric Framework, we show that a low-protein intake, coupled with a balanced intake of carbohydrate and fat is optimal for wound healing. Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production. These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure, related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots. CONCLUSIONS: The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.

Skin wound repair: Results of a pre-clinical study to evaluate electropsun collagen-elastin-PCL scaffolds as dermal substitutes.

The gold standard treatment for severe burn injuries is autologous skin grafting and the use of commercial dermal substitutes. However, resulting skin tissue following treatment usually displays abnormal morphology and functionality including scarring, skin contracture due to the poor elasticity and strength of existing dermal substitutes. In this study, we have developed a triple-polymer scaffold made of collagen-elastin-polycaprolactone (CEP) composite, aiming to enhance the mechanical properties of the scaffold while retaining its biological properties in promoting cell attachment, proliferation and tissue regeneration. The inclusion of elastin was revealed to decrease the stiffness of the scaffold, while also decreasing hysteresis and increasing elasticity. In mice, electrospun collagen-elastin-PCL scaffolds promoted keratinocyte and fibroblast proliferation, tissue integration and accelerated early-stage angiogenesis. Only a mild inflammatory response was observed in the first 2 weeks post-subcutaneous implantation. Our data indicates that the electrospun collagen-elastin-PCL scaffolds could potentially serve as a skin substitute to promote skin cell growth and tissue regeneration after severe burn injury.

Tropoelastin incorporation into a dermal regeneration template promotes wound angiogenesis.

Severe burn injury results in substantial skin loss and cannot be treated by autografts. The Integra Dermal Regeneration Template (IDRT) is the leading synthetic skin substitute because it allows for wound bed regeneration and wound healing. However, all substitutes suffer from slow blood vessel ingrowth and would benefit considerably from enhanced vascularization to nurture tissue repair. It is shown here that by incorporating the human elastic protein tropoelastin into a dermal regeneration template (TDRT) we can promote angiogenesis in wound healing. In small and large animal models comprising mice and pigs, the hybrid TDRT biomaterial and IDRT show similar contraction to autografts and decrease wound contraction compared to open wounds. In mice, TDRT accelerates early stage angiogenesis by 2 weeks, as evidenced by increased angiogenesis fluorescent radiant efficiency in live animal imaging and the expression of endothelial cell adhesion marker CD146. In the pig, a full thickness wound repair model confirms increased numbers of blood vessels in the regenerating areas of the dermis closest to the hypodermis and immediately below the epidermis at 2 weeks post-surgery. It is concluded that including tropoelastin in a dermal regeneration template has the potential to promote wound repair through enhanced vascularization.

An electrospun scaffold loaded with anti-androgen receptor compound for accelerating wound healing.

Current dermal regenerative scafolds provide wound coverage, and structural support and guidance for tissue repair, but usually lack enough bio-signals needed for speeding up skin cell growth, migration, wound closure, and skin regeneration. In this study, an androgen receptor (AR) inhibitor called ASC-J9 is used to demonstrate the concept and feasibility of fabricating drug-loaded scafolds via electrospinning. Inhibition of androgen is known to promote skin wound healing. The novel ASC-J9 - loaded porous scafold was fabricated for skin wound repair using electrospun fibers of collagen and polycaprolactone (PCL) blend. Our preliminary results indicated that ASC-J9 - loaded scafolds facilitated more efficient attachment and ingrowth of dermal fbroblasts, compared to the control collagen-PCL scafold. A signifcant increase of cell proliferation was observed with the drug-loaded scafold over a 28-day period. The drug-loaded scafold also accelerated keratinocyte migration and wound closure in a contraction-inhibited mouse wound model over 21 days. The data indicated a sustained release of ASC-J9 from the scafold and its potential to accelerate wound healing by promoting cell proliferation and migration over an extended period of time. More importantly, our results proved the concept and feasibility of fabricating drug-releasing or bioactive dermal scaffolds for more efective wound healing.