RESUMO
Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re-epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.
RESUMO
Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.
Assuntos
Músculo Esquelético/lesões , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Ferimentos e Lesões/terapia , Animais , Camundongos , Fator A de Crescimento do Endotélio VascularRESUMO
In this study, we successfully applied a previously modified version of the QuEChERS approach to quantify pesticide residues in samples of fresh salmon. Analysis was performed using a combination of liquid and gas chromatography-tandem mass spectrometry (LC-MS/MS and GC-MS/MS). The validated QuEChERS method used ethyl acetate for the extraction solvent and involved two freezing steps and a C18 dispersive solid phase extraction for removal of lipids. Of the 228 pesticides initially screened, only 185 passed the method validation criteria (103 on LC-MS/MS and 82 on GC-MS/MS). In a quantitative validation, acceptable performances were achieved with overall recoveries of 70-120% and <20% RSD for 179 analytes (n = 7) over the course of five different extractions at 2 times the limit of quantification. Over 12 months, this method was used in the analysis of 708 salmon samples collected as part of the U.S. Department of Agriculture's Pesticide Data Program. Ruggedness testing conducted throughout the entire study showed this method to be robust and suitable for long-term use.