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Negative Pressure Wound Therapy with Instillation Accelerates the Granulation Response with Gene Expression Variations While Maintaining Comparable Tissue Quality Compared to Continuous and Non-Continuous Negative Pressure Wound Therapy in a Porcine Model
Diwi Allen, MS, Chris Lessing, PhD, Kathleen Derrick, MS, Roberta James, MS, Shannon Ingram, PE.
KCI, San Antonio, TX, USA.
PURPOSE: Negative pressure wound therapy (NPWT*) can be coupled with automated delivery and removal of topical wound treatment solutions and suspensions (NPWTi†) or delivered in either continuous or non-continuous modes. This porcine study compared the granulation response, genomic response, and resulting tissue quality of NPWTi using normal saline with instillation foam dressing‡ to NPWT using standard foam dressing§ in continuous and non-continuous modes. The quality of the resulting granulation tissue was assessed using these key measures: collagen content, angiogenesis, extracellular matrix components, and cellular energetics.
METHODS: Full-thickness dorsal excisional wounds in pigs were treated with continuous NPWT, intermittent NPWT, dynamic (controlled variable) NPWT, and NPWTi with saline. Wound dimensions were determined from 3-D images collected on Days 0, 2, 5, and 7. On Day 7, animals were euthanized and specimens were collected for histopathological review and downstream processing for RNA and total protein. Gene expression was measured by quantitative real-time PCR. Tissue quality was assessed via enzyme-linked immunosorbent assays evaluating the following porcine-specific proteins: collagen type 1, vascular endothelial growth factor (VEGF), fibronectin, vitronectin, and cytochrome C oxidase.
RESULTS: Average granulation thickness of NPWTi with saline wounds was statistically greater (p<0.05) by 44%, 57%, and 40% than continuous, intermittent, and dynamic NPWT wounds, respectively. Per 3-D image analysis, NPWTi wounds revealed greater reduction in wound area and perimeter compared to all NPWT wounds (p<0.05) with a faster wound fill rate than continuous (40%; p<0.05), intermittent (25%; p>0.05), and dynamic (65%; p<0.05) NPWT wounds. Regarding gene expression, NPWTi was similar to that of continuous NPWT with some key differences. Genes for Tenascin C (an extracellular matrix, or ECM, glycoprotein) and urokinase plasminogen activator receptor (a mediator of ECM remodeling) were expressed 1.88 and 1.55 times greater, respectively, in NPWTi wounds than intermittent NPWT. Similarities in gene expression included collagen type I alpha 1 and colony stimulating factor 2 (over-expressed 2 times in both NPWTi and continuous NPWT compared to intermittent and dynamic NPWT). Regarding tissue quality, collagen type 1 content for NPWTi was comparable to NPWT in continuous and non-continuous modes and similar to unwounded tissue (~2000pg/ml per µg total protein). No difference was found between NPWTi and NPWT wounds regarding VEGF content, ~600pg/ml per mg. Vitronectin and fibronectin levels were also similar when comparing NPWTi to NPWT (~8000pg/ml per µg, and ~1225pg/ml per mg, respectively). Analysis of cytochrome C oxidase content also revealed similar levels, at ~12500pg/ml per mg, comparing NPWTi and NPWT wounds.
CONCLUSION: These porcine data suggest that NPWTi with saline may stimulate a faster rate of wound granulation than NPWT in continuous and non-continuous modes. This study also suggests that NPWTi may positively influence the expression of genes associated with wound healing and stimulate wound granulation with comparable vascular and matrix quality as continuous or non-continuous NPWT.
*V.A.C.® Therapy, †V.A.C. VeraFlo™ Therapy, ‡V.A.C. VeraFlo™ Dressing, §V.A.C.® GranuFoam™ Dressing (KCI USA, Inc., San Antonio, TX)
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