Enhancing the Study of Negative Pressure Wound Therapy in a Porcine Model
Ashley L. Pistorio, MD, MS1, Christopher A. Neal, PhD1, Heather E. Shinogle-Decker, BA2, Jennifer G. Nelson-Brantley, BS1, Molly Steed, PharmD2, Richard Korentager, MD1, David S. Zamierowski, MD1, Adam J. Mellott, PhD1.
1University of Kansas Medical Center, Kansas City, KS, USA, 2University of Kansas, Lawrence, KS, USA.
PURPOSE: Negative pressure wound therapy (NPWT) has been used as an effective surgical adjunct technique for accelerating the closure of acute and chronic wounds for nearly two decades. NPWT is used in battlefield trauma and routinely in the operating room to close a variety of full thickness and partial thickness wounds. Considerable efforts have been invested into elucidating the cellular and molecular mechanisms behind the efficacy of NPWT; however, these mechanisms are still not fully understood due to challenges in directly observing NPWT histologically, in real-time. The ability to observe how the polyurethane foam dressing interfaces with the wound bed and surrounding tissue over time, would provide significant insights into some mechanisms of NPWT in wound healing and wound closure.
METHODS: In the work presented, a series of full thickness wounds were made in a porcine model, and the character of the wound bed was assessed over nine days when exposed to NPWT and without NPWT. A specialized multiplex format was used to execute multiple analyses on each wound in parallel to maximize the data collected for each sample while reducing the number of animals needed and minimizing the discomfort of each animal.
RESULTS: Analysis of tissue layers at post-wound day 9 showed an increase in keratin thickness in the wounds treated with NPWT, while keratin thickness decreased in wounds without NPWT. Epidermal thickness was increased in NPWT treated wounds and even more increased in non-NPWT treated wounds. Dermal thickness increased in non-NPWT treated wounds compared against native tissue and NPWT treated wounds. Bacterial infiltration was shown in the keratin layer with gram positive and negative species, but gram negative bacteria were also found to be embedded within GranuFoam at the wound interface as well as infiltrating the epidermis and dermis wounds treated with NPWT. Non-NPWT treated wounds displayed gram negative bacteria within the borders of the GranuFoam and throughout the epidermis, dermis, and subcutaneous layer. There was decreased transcript expression of type 1 collagen, type 4 collagen, matrix metalloproteinase 7 and smooth muscle actin in NPWT treated wounds compared to non-NPWT treated wounds.
CONCLUSION: Our findings are the first to histologically capture the in-growth of the granulation tissue as well as infiltration of dermal fibroblasts into the polyurethane foam dressing while wound sites are under negative pressure. Furthermore, our findings raise new questions regarding the direct and indirect effects of NPWT stimulation of cell proliferation and extracellular matrix remodeling, which may have implications for enhancing repair of other critical defects in soft tissues using deformable biomaterials that alter the surrounding tissue.
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