It Takes Two to Tangle: Microneedle Patches Co-delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms.

Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL-1 W379 and 250 ng mL-1 anti-BPB2a decreases the bacterial count from ≈3.31 × 107 CFU mL-1 to 1.28 × 102 CFU mL-1 within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.

Outcomes of Negative Pressure Wound Therapy on Immediate Breast Reconstruction after Mastectomy.

Immediate expander/implant-based breast reconstruction after mastectomy has become more sought after by patients. Although many patients choose this technique due to good aesthetic outcomes, lack of donor site morbidity, and shorter procedure times, it is not without complications. The most reported complications include seroma, infection, hematoma, mastectomy flap necrosis, wound dehiscence, and implant exposure, with an overall complication rate as high as 45%. Closed incision negative pressure therapy (ciNPT) has shown value in wound healing and reducing complications; however, the current literature is inconclusive. We aimed to examine if ciNPT improves outcomes for patients receiving this implant-based reconstruction. Methods: This is a retrospective single-institution study evaluating the ciNPT device, 3M Prevena Restor BellaForm, on breast reconstruction patients. The study was performed between July 1, 2019 and October 30, 2020, with 125 patients (232 breasts). Seventy-seven patients (142 breasts) did not receive the ciNPT dressing, and 48 patients (90 breasts) received the ciNPT dressing. Primary outcomes were categorized by major or minor complications. Age, BMI, and final drain removal were summarized using medians and quartiles, and were compared with nonparametric Mann-Whitney test. Categorical variables were compared using chi-square or Fisher exact test. Results: There was a statistically significant reduction in major complications in the ciNPT group versus the standard dressing group (P = 0.0247). Drain removal time was higher in the ciNPT group. Conclusion: Our study shows that ciNPT may help reduce major complication rates in implant-based breast reconstruction patients.

Triggered release of antimicrobial peptide from microneedle patches for treatment of wound biofilms.

Biofilms pose a great challenge for wound management. Herein, this study describes a near-infrared (NIR) light-responsive microneedle patch for on-demand release of antimicrobial peptide for treatment of wound biofilms. IR780 iodide as a photothermal conversion agent and molecularly engineered peptide W379 as an antimicrobial agent are loaded in dissolvable poly(vinylpyrrolidone) (PVP) microneedle patches followed by coating with a phase change material 1-tetradecanol (TD). After placing in an aqueous solution or biofilm containing wounds ex vivo and in vivo, upon exposure to NIR light, the incorporated IR780 induces light-to-heat conversion, causing the melting of TD. This leads to the dissolution of PVP microneedles, enabling the release of loaded W379 peptide from the microneedles into surrounding regions (e.g., solution, biofilm, wound bed). Compared with traditional microneedle patches, NIR light responsive microneedle patches can program the release of antimicrobial peptide and show high antibacterial efficacy in vitro. Meanwhile, this work indicates that NIR light responsive TD-coated, W379-loaded PVP microneedle patches show excellent antibiofilm activities ex vivo and in vivo. Additionally, this microneedle system could be a promising platform for delivering other antimicrobial agents.

Cross-Suturing is Effective for Teaching Suturing Skills: A Randomized, Controlled Trial.

INTRODUCTION: Basic suturing is a skill expected from graduating medical students. A proposed concept to increase suturing competency is to integrate art by mixing cross-stitching with suturing. We hypothesize that students trained with "cross-suturing" would improve suturing performance. METHODS: We performed a randomized controlled trial of preclinical medical students using an art-based cross-stitching method intervention compared with conventional suturing. Both groups were provided with an introductory suturing video. Assessment of simple interrupted suturing were conducted preintervention and postintervention, and at 2-wk follow-up with a video review by blinded expert raters using the American College of Surgeons basic suturing and knot tying performance rating tool. Students completed a self-assessment of proficiency, confidence, and anxiety. Statistical analysis was performed using unpaired t-tests. RESULTS: A total of 16 preclinical medical students participated. Self-assessment and objective suturing performance were comparable in the preintervention measurements. The intervention group showed significant improvement compared to the control group with median (interquartile range) self-assessment scores 9 (8.5-9) compared with 6.5 (6-7.5) (P < 0.01) and objective performance scores of 25.25 (22.75-27) compared with 16.5 (14.5-18.5) (P < 0.01). The intervention group showed retained skills at the 2-wk follow up with no differences in self-assessment or objective suturing scores immediately postintervention compared with two-wk follow-up with self-assessment scores of 9 (8.5-9) versus 9 (8-9) at 2 wk (P = 0.16) and objective performance score of 25.25 (22.75-27) versus 24.75 (23.5-26.5) at 2 wk (P = 0.29). CONCLUSIONS: The cross-suturing intervention improved suturing skills in this cohort. This low-cost approach to medical student surgical education should be explored on a larger scale.

Codelivery of 1α,25-Dihydroxyvitamin D3 and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.

Surgical site infections represent a significant clinical problem. Herein, we report a nanofiber dressing for topical codelivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and VID400, a CYP24A1 inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide (CAMP) gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)2D3 and VID400 were generated by electrospinning. Both 1,25(OH)2D3 and VID400 were coencapsulated into nanofibers with loading efficiencies higher than 90% and exhibited a prolonged release from nanofiber membranes longer than 28 days. Incubation with 1,25(OH)2D3/VID400-coencapsulated poly(ϵ-caprolactone) nanofiber membranes greatly induced the hCAP18/LL-37 gene expression in monocytes, neutrophils, and keratinocytes in vitro. Moreover, the administration of 1,25(OH)2D3/VID400-coencapsulated nanofiber membranes dramatically promoted the hCAP18/LL-37 expression in dermal wounds created in both human CAMP transgenic mice and human skin tissues. The 1,25(OH)2D3- and VID400-coencapsulated nanofiber dressings enhanced innate immunity via the more effective induction of antimicrobial peptide than the free drug alone or 1,25(OH)2D3-loaded nanofibers. Together, 1,25(OH)2D3/VID400-embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.

Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms.

Biofilms pose a major challenge to control wound-associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO3 , Ga(NO3 )3 , and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents-incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin-resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.

Dissolvable Microneedles Coupled with Nanofiber Dressings Eradicate Biofilms via Effectively Delivering a Database-Designed Antimicrobial Peptide.

Biofilms in chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Herein, we report a Janus-type antimicrobial dressing for eradication of biofilms in chronic wounds. The dressing consists of electrospun nanofiber membranes coupled with dissolvable microneedle arrays to enable effective delivery of a database-designed antimicrobial peptide to both inside and outside biofilms. This antimicrobial dressing exhibited high efficacy against a broad spectrum of resistant pathogens in vitro. Importantly, such a dressing was able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms in both an ex vivo human skin wound infection model and a type II diabetic mouse wound infection model after daily treatment without applying surgical debridement. Most importantly, the dressing can also completely remove the Pseudomonas aeruginosa and MRSA, dual-species biofilm in an ex vivo human skin infection model. In addition, our computational simulations also suggested that microneedles were more effective in the delivery of peptides to the biofilms than free drugs. Our results indicate that the Janus-type antimicrobial dressings may provide an effective treatment and management of chronic wound polymicrobial infections.

Mesenchymal stem cell-laden, personalized 3D scaffolds with controlled structure and fiber alignment promote diabetic wound healing.

The management of diabetic wounds remains a major therapeutic challenge in clinics. Herein, we report a personalized treatment using 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with bone marrow mesenchymal stem cells (BMSCs). The 3D scaffolds have customizable sizes, depths, and shapes, enabling them to fit a variety of type 2 diabetic wounds. In addition, the 3D scaffolds are shape-recoverable in atmosphere and water following compression. The BMSCs-laden 3D scaffolds are capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition. Further, such scaffolds inhibit the formation of M1-type macrophages and the expression of pro-inflammatory cytokines IL-6 and TNF-α and promote the formation of M2-type macrophages and the expression of anti-inflammatory cytokines IL-4 and IL-10. Taken together, BMSCs-laden, 3D nanofiber scaffolds with controlled structure and alignment hold great promise for the treatment of diabetic wounds. STATEMENT OF SIGNIFICANCE: In this study, we developed 3D radially and vertically aligned nanofiber scaffolds to transplant bone marrow mesenchymal stem cells (BMSCs). We personalized 3D scaffolds that could completely match the size, depth, and shape of diabetic wounds. Moreover, both the radially and vertically aligned nanofiber scaffolds could completely recover their shape and maintain structural integrity after repeated loads with compressive stresses. Furthermore, the BMSCs-laden 3D scaffolds are able to promote granulation tissue formation, angiogenesis, and collagen deposition, and switch the immune responses to the pro-regenerative direction. These 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with BMSCs offer a robust, customizable platform potentially for a significant improvement of managing diabetic wounds.

The absorbable dermal staple device: a faster, more cost-effective method for incisional closure.

BACKGROUND: Closure with dermal sutures is time consuming, may increase the risks of inflammation and infection secondary to foreign body reaction, exposes the surgeon to possible needlestick injuries, and has variable cosmetic outcomes depending on each surgeon's technique. The absorbable INSORB dermal stapler is hypothesized to be faster and more cost effective than sutures for dermal layer closures and provides a safer and more consistent result. METHODS: This is a prospective, randomized, controlled study. Patients undergoing bilateral breast reconstruction with tissue expanders had one incision randomized to dermal closure with absorbable dermal staples. The contralateral side was closed with dermal sutures. During the expansion period, wounds were assessed by a blinded plastic surgeon using the 13-point Vancouver Scar Scale. At the time of implant exchange, both scars were excised and examined for histologic signs of inflammation. RESULTS: Eleven patients (22 incisions) were enrolled in the study. The dermal stapler was four times faster than standard suture closure, reducing closure time by 10.5 minutes (p