Efficacy of Topical Treatments for Chrysaora chinensis Species: A Human Model in Comparison with an In Vitro Model.

OBJECTIVES: This study sought to create a model for testing topical treatment of jellyfish stings. It sought to determine which treatments 1) stimulate/inhibit nematocyst discharge; 2) decrease pain; and 3) decrease skin inflammation; it also sought to discover whether there is a clinical correlation between stimulated nematocyst discharge observed in vitro to the pain and erythema experienced by humans stung by a particular species of jellyfish, C chinensis. METHODS: Chrysaora chinensis stung 96 human subjects, who were then treated with isopropyl alcohol, hot water, acetic acid, papain meat tenderizer, lidocaine, or sodium bicarbonate. Pain and erythema were measured. In a separate experiment, nematocysts were examined microscopically after exposure to the same topical treatments used in the human experiment. RESULTS: Forearms treated with papain showed decreased mean pain over the first 30 minutes after being stung, relative to placebo, although only by a small amount. The other topical treatments tested did not reach statistical significance. Sodium bicarbonate may reduce erythema after 30 minutes of treatment; sodium bicarbonate and papain may reduce erythema at 60 minutes. The other topical treatments tested did not reach statistical significance. Nematocyst discharge in vitro occurred when tentacles of C chinensis were exposed to acetic acid or isopropyl alcohol. Sodium bicarbonate, papain, heated water, and lidocaine did not induce nematocyst discharge. CONCLUSIONS: Papain-containing meat tenderizer used as a topical treatment for C chinensis stings may decrease pain. Although there is published experimental support for the concept that in vitro nematocyst discharge correlates with in vivo human pain perception, no definitive randomized controlled trial, including ours, has yet provided incontrovertible evidence of this assertion. Despite this study's limitations, it presents a viable basis for future human studies looking at the efficacy of topical treatments for jellyfish stings.

Poly-L-arginine topical lotion tested in a mouse model for frostbite injury.

BACKGROUND: Frostbite injury occurs when exposure to cold results in frozen tissue. We recently reported a novel mouse model for frostbite injury to be used in screening potentially therapeutic drugs and other modalities. OBJECTIVE: We used the mouse skin frostbite model to evaluate the effect of poly-l-arginine contained in lotion (PAL) applied topically to involved skin. METHODS: Sixty mice were studied in a randomized, double-blind method. Standardized 2.9-cm-diameter circles were tattooed on the mouse dorsum. Magnets snap frozen in dry ice (-78.5°C) were used to create a frostbite injury on skin within the circle as a continuous 5-minute freeze. Mice were treated with prefreeze placebo, postthaw placebo, combined prefreeze and postthaw placebo, prefreeze with PAL, postthaw with PAL, or combined prefreeze and postthaw with PAL. Appearance, healing rate, tissue loss, and histology were recorded until the wounds were healed. RESULTS: Application of PAL before inducing frostbite injury resulted in decreased tissue loss as compared with other treatment conditions. CONCLUSIONS: Applying PAL topically to frostbitten mouse skin caused decreased tissue loss. Poly-l-arginine should be studied further to determine whether it is a beneficial therapeutic modality for frostbite injury.

A novel mouse model for frostbite injury.

BACKGROUND: Frostbite injury occurs when exposure to cold results in frozen tissue. To screen drugs and other field therapies that might improve the outcome for a frostbite victim, it would be helpful to have a reliable and cost-effective preclinical in vivo model. OBJECTIVE: We sought to create a novel mouse skin model of induced frostbite injury. This model would allow quantification of the surface area of involved skin, histology of the wound, rate of wound healing, and skin loss in a standardized fashion after the frostbite injury. METHODS: Thirty-six mice were studied. Standardized 2.9-cm diameter circles were tattooed on the mouse dorsum. Magnets frozen in dry ice (-78.5°C) were used to create a frostbite injury on skin within the circle, either as a continuous 5-minute freeze or as 3 repeated freeze (1-minute) and thaw (3-minute) cycles. Appearance, healing rate, skin surface area loss, and histology were recorded until the wounds were healed. RESULTS: The amount of skin surface area loss was approximately 50% for both freeze methods. Although the time to surface skin healing was similar for both freeze methods, the initial healing rate was significantly (P = .001) slower in mice exposed to the freeze-thaw cycles compared with the continuous freeze model. Histopathology reflected inflammatory changes, cell death, and necrosis. CONCLUSIONS: This novel in vivo mouse model for frostbite allows quantification of affected skin surface area, histology, healing rate, and skin loss and has the potential of being utilized to screen future treatment modalities.

Capillary force seeding of hydrogels for adipose-derived stem cell delivery in wounds.

Effective skin regeneration therapies require a successful interface between progenitor cells and biocompatible delivery systems. We previously demonstrated the efficiency of a biomimetic pullulan-collagen hydrogel scaffold for improving bone marrow-derived mesenchymal stem cell survival within ischemic skin wounds by creating a "stem cell niche" that enhances regenerative cytokine secretion. Adipose-derived mesenchymal stem cells (ASCs) represent an even more appealing source of stem cells because of their abundance and accessibility, and in this study we explored the utility of ASCs for hydrogel-based therapies. To optimize hydrogel cell seeding, a rapid, capillary force-based approach was developed and compared with previously established cell seeding methods. ASC viability and functionality following capillary hydrogel seeding were then analyzed in vitro and in vivo. In these experiments, ASCs were seeded more efficiently by capillary force than by traditional methods and remained viable and functional in this niche for up to 14 days. Additionally, hydrogel seeding of ASCs resulted in the enhanced expression of multiple stemness and angiogenesis-related genes, including Oct4, Vegf, Mcp-1, and Sdf-1. Moving in vivo, hydrogel delivery improved ASC survival, and application of both murine and human ASC-seeded hydrogels to splinted murine wounds resulted in accelerated wound closure and increased vascularity when compared with control wounds treated with unseeded hydrogels. In conclusion, capillary seeding of ASCs within a pullulan-collagen hydrogel bioscaffold provides a convenient and simple way to deliver therapeutic cells to wound environments. Moreover, ASC-seeded constructs display a significant potential to accelerate wound healing that can be easily translated to a clinical setting.