Preclinical Assessments of a Novel Peel and Place Extended-Wear Negative-Pressure Wound Therapy Dressing for up to 35 Days in a Porcine Model.

Objective: While the use of negative pressure wound therapy (NPWT) with reticulated open cell foam (ROCF) is well established, the characteristics of ROCF do not allow for extended-wear use. There is the potential for dressing tissue ingrowth if left in place for greater than the recommended 2-3 days. An easy to use, novel peel and place dressing has been designed for extended wear with the wound management advantages of ROCF while alleviating the challenges of tissue ingrowth. Approach: Paraspinal, full-thickness or deep muscle excisional wounds were created in 11 and 2 swine, respectively, dressings applied with continuous negative pressure at -125 mmHg, and dressings changed weekly. Full-thickness excisional wounds were treated for 13 days and deep muscle wounds for 35 days. Wound dimensions were assessed. Granulation tissue thickness and re-epithelialization were measured via digital morphometry. Tissue quality, fibrinous material prevalence, and dressing removal peel force were analyzed. Results: The peel and place dressing substantially reduces dressing tissue ingrowth, is easy to remove with markedly low dressing peel force and promotes more granulation tissue at day 13 than ROCF with an interface layer. The extended-wear peel and place dressing, when applied to deep muscle wounds with weekly dressing changes, was applied for a total of 35 days. Successful wound closure was evident without any negative impact on wound healing. Innovation: This study assessed the wound management capabilities of an extended-wear peel and place NPWT dressing used until wound closure. Conclusion: The peel and place dressing is a suitable extended-wear NPWT dressing.

Preclinical assessment of novel longer-duration wear negative pressure wound therapy dressing in a porcine model.

While reticulated open cell foam (ROCF) is a well-established dressing for negative pressure wound therapy (NPWT), there is the known potential for granulation tissue ingrowth if left in place for longer than 72 h. This may cause wound bed disruption, bleeding, and pain upon dressing removal. In addition, any retained foam fragments may elicit an adverse tissue reaction. A novel, easy to use dressing designed to utilise the advantages of ROCF while addressing its challenges has recently been created. This 7 day study investigated the utility of a novel NPWT dressing under longer-duration wear circumstances while assessing the prevalence of tissue ingrowth and ease of dressing removal in full-thickness excisional wounds utilising a porcine model. Histopathology and morphometry evaluations indicated thicker granulation tissue with, depending on the parameters assessed, either comparable or better tissue quality for wounds treated with the novel dressing. Greater re-epithelialization levels were also evident compared with ROCF. Three-dimensional imaging analysis indicated faster wound fill with a corresponding decrease in wound area with the novel dressing. Furthermore, tissue ingrowth was limited to only ROCF-treated wounds, which was not unexpected in this longer-duration wear study. The force required to remove the novel dressing was considerably lower compared with ROCF, correlating to the tissue ingrowth results. Results of this study illustrate that the novel dressing provided more favourable wound healing results compared with traditional ROCF. In addition, reduction in the risk of tissue ingrowth and low dressing peel force may allow it to be used as a longer-wear dressing.

Comparison of tissue damage, cleansing and cross-contamination potential during wound cleansing via two methods: lavage and negative pressure wound therapy with instillation.

The use of lavage was compared to negative pressure wound therapy (NPWT) with instillation (NPWTi) to assess extent of soft tissue damage, debris removal and environmental cross-contamination susceptibility in three distinct models. Scanning electron microscopy in an ex vivo model showed increased visible tissue trauma from lavage treatment at low and high pressures versus NPWTi, with the degree of trauma relative to the pressure of the irrigant. These results were corroborated in granulating full-thickness excisional swine wounds coated with dextran solution to simulate wound debris. Both low-pressure lavage and NPWTi demonstrated effective cleansing in this model, reducing debris by >90%. However, using three-dimensional photography to evaluate tissue damage by measuring immediate tissue swelling (changes in wound volume and depth) showed significantly greater (P < 0.05) swelling in low-pressure lavage-treated wounds compared with NPWTi-treated wounds. Lastly, bench top wound models were inoculated with fluorescent bacterial particles to assess environmental cross-contamination potential and collected at measured distances after treatment with low-pressure lavage and NPWTi. No evidence of cross-contamination was found with NPWTi, whereas one-half of the particles became 'aerosolised' during low-pressure lavage (P < 0.05). Collectively, these studies demonstrate the effective wound cleansing capabilities of NPWTi without the tissue damage and environmental contamination associated with lavage.

Science supporting negative pressure wound therapy with instillation.

A new method (V.A.C.ULTA Therapy System, KCI USA, Inc., San Antonio, TX) combines the benefits of negative pressure wound therapy (NPWT; V.A.C. Therapy, KCI USA, Inc.) with regulated, periodic instillation of user-selected topical wound solutions (V.A.C. VeraFlo Therapy, KCI USA, Inc.). In simulated wound model studies comparing solution distribution using NPWT with and without a soak phase, the instillation soak phase allowed for uniform solution distribution across the wound bed, whereas continuous (no soak) irrigation resulted in uneven coverage. Additional in vitro work illustrated that bacterial particle aerosolisation during wound cleansing was significantly decreased using NPWT with instillation (NPWTi) versus commercially available low-pressure wound cleansers (P < 0·05). In porcine studies, NPWT with saline instillation induced 43% more granulation tissue versus NPWT (P < 0·05) and was as effective at wound cleansing as pulsed lavage. These studies have demonstrated that NPWTi may be an effective wound management therapy that provides both wound cleansing and NPWT benefits.

The effects of normal saline instillation in conjunction with negative pressure wound therapy on wound healing in a porcine model.

UNLABELLED: Acute and chronic wounds impact the lives of millions of patients. Since its introduction, negative pressure wound therapy using reticulated open cell foam (NPWT/ROCF) has significantly improved the healing outcome for many of these wounds. METHODS: The effects of intermittent instillation of normal saline in conjunction with NPWT were investigated to determine if instillation therapy provides additional benefits in wound healing. Conventional NPWT/ROCF as delivered by V.A.C.® Therapy was compared to V.A.C. Instill® Therapy with normal saline in the treatment of porcine full-thickness excisional wounds. Wounds were treated with NPWT/ROCF or NPWT/ROCF with instillation therapy at approximately 4 cycles of normal saline instillation per day and dwell times of either 5 or 60 minutes for the instilled saline on the wound bed. RESULTS: Instillation therapy with normal saline at either dwell time elicited a faster rate of wound filling with granulation tissue that contained an increase in total collagen content compared to continuous NPWT/ROCF alone. Analyses of wound contraction and the hydration state of the treated tissue exhibited no apparent differences between the experimental instillation therapy groups and the control NPWT/ROCF group. CONCLUSION: Collectively, these data suggest that instillation therapy with normal saline may lead to wound fill with higher quality granulation tissue composed of increased collagen following wounding of cutaneous tissue compared to the use of NPWT/ROCF alone.  .

Mutagenesis is elevated in male germ cells obtained from DNA polymerase-beta heterozygous mice.

Gametes carry the DNA that will direct the development of the next generation. By compromising genetic integrity, DNA damage and mutagenesis threaten the ability of gametes to fulfill their biological function. DNA repair pathways function in germ cells and serve to ameliorate much DNA damage and prevent mutagenesis. High base excision repair (BER) activity is documented for spermatogenic cells. DNA polymerase-beta (POLB) is required for the short-patch BER pathway. Because mice homozygous null for the Polb gene die soon after birth, mice heterozygous for Polb were used to examine the extent to which POLB contributes to maintaining spermatogenic genomic integrity in vivo. POLB protein levels were reduced only in mixed spermatogenic cells. In vitro short-patch BER activity assays revealed that spermatogenic cell nuclear extracts obtained from Polb heterozygous mice had one third the BER activity of age-matched control mice. Polb heterozygosity had no effect on the BER activities of somatic tissues tested. The Polb heterozygous mouse line was crossed with the lacI transgenic Big Blue mouse line to assess mutant frequency. The spontaneous mutant frequency for mixed spermatogenic cells prepared from Polb heterozygous mice was 2-fold greater than that of wild-type controls, but no significant effect was found among the somatic tissues tested. These results demonstrate that normal POLB abundance is necessary for normal BER activity, which is critical in maintaining a low germline mutant frequency. Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency.