Skin treatment with non-thermal plasma modulates the immune system through miR-223-3p and its target genes.

Non-thermal plasma, a partially ionized gas, holds significant potential for clinical applications, including wound-healing support, oral therapies, and anti-tumour treatments. While its applications showed promising outcomes, the underlying molecular mechanisms remain incompletely understood. We thus apply non-thermal plasma to mouse auricular skin and conducted non-coding RNA sequencing, as well as single-cell blood sequencing. In a time-series analysis (five timepoints spanning 2 hours), we compare the expression of microRNAs in the plasma-treated left ears to the unexposed right ears of the same mice as well as to the ears of unexposed control mice. Our findings indicate specific effects in the treated ears for a set of five miRNAs: mmu-miR-144-5p, mmu-miR-144-3p, mmu-miR-142a-5p, mmu-miR-223-3p, and mmu-miR-451a. Interestingly, mmu-miR-223-3p also exhibits an increase over time in the right non-treated ear of the exposed mice, suggesting systemic effects. Notably, this miRNA, along with mmu-miR-142a-5p and mmu-miR-144-3p, regulates genes and pathways associated with wound healing and tissue regeneration (namely ErbB, FoxO, Hippo, and PI3K-Akt signalling). This co-regulation is particularly remarkable considering the significant seed dissimilarities among the miRNAs. Finally, single-cell sequencing of PBMCs reveals the downregulation of 12 from 15 target genes in B-cells, Cd4+ and Cd8+ T-cells. Collectively, our data provide evidence for a systemic effect of non-thermal plasma.

Aesthetic Implications of Bilateral Profunda Artery Perforator Flaps on Thigh and Buttock Proportions.

BACKGROUND: The profunda artery perforator (PAP) flap has emerged as an excellent secondary option for autologous breast reconstruction. Despite the increased acceptance, potential secondary benefits concerning aesthetic proportions of proximal thigh and buttock at the donor site have never been systematically investigated. METHODS: A retrospective review of 151 patients who underwent breast reconstruction with horizontally designed PAP flaps (292 flaps) from 2012 to 2020 was performed. Patient characteristics, complications, and numbers of revision surgeries were collected. In bilateral reconstructions, pre- and postoperative standardized patient photographs were analyzed to identify postoperative changes in proximal thigh and buttock contour. The patients' own perception of postoperative aesthetic changes was determined by an electronic survey. RESULTS: The patients had a mean age of 51 and a mean body mass index of 26.3 kg/m2. The most common complications were minor and major wound complications affecting 35.1% of patients, followed by cellulitis (12.6%), seroma (7.9%), and hematoma (4.0%). A total of 38 patients (25.2%) underwent revision of the donor site. After reconstruction, patients were found to have aesthetically improved proximal thigh and buttock proportions, indicated by a wider thigh gap (thigh gap-hip ratio: 0.05 ± 0.04 vs. 0.13 ± 0.05, p < 0.0001) and reduction in lateral thigh-to-buttock ratio (0.85 ± 0.05 vs. 0.76 ± 0.05, p < 0.0001). Among the 85 patients who responded to the survey (56.3% response rate), 70.6% felt that PAP surgery had aesthetically either improved their thigh contour (54.12%) or not changed it (16.47%), whereas only 29.4% reported that the surgery negatively impacted their thigh contour. CONCLUSION: PAP flap breast reconstruction leads to improved aesthetic proportions of the proximal thigh and buttock. This approach is ideal for patients with ptotic tissue of the inferior buttocks and medial thigh, a poorly defined infragluteal fold, and inadequate anterior-posterior buttock projection.

Breast Reconstruction With Simultaneous Bilateral Lumbar Artery Perforator Flaps Improves Waistline Definition and Buttock Projection.

BACKGROUND: The lumbar artery perforator (LAP) flap is a valuable secondary option for autologous breast reconstruction when abdominal donor sites are not available. OBJECTIVES: The aim of this study was to determine how the LAP donor site affects waistline and gluteal proportions, and whether LAP flaps may produce potential secondary benefits concerning donor site aesthetics. METHODS: A retrospective review of 50 patients who underwent bilateral breast reconstruction with LAP flaps (100 flaps) between 2018 and 2022 was performed. Patient characteristics and postoperative complications were recorded. Pre- and postoperative standardized frontal and lateral patient photographs were analyzed to identify postoperative changes in waist-to-hip ratio (WHR) to assess waistline definition and buttock projection. The patients' individual perception of postoperative aesthetic changes to their waistline and buttocks was determined by an electronic survey. RESULTS: The patients had a mean age of 51 years (range, 24-63 years) and a mean BMI of 26.9 kg/m2 (range, 19.3-37.4 kg/m2). Postoperative donor site complications included seroma (n = 10), wound dehiscence (n = 5), hematoma (n = 4), and wound infection (n = 2). Flap loss rate was 2%. After reconstruction, patients were found to have a more defined waistline, indicated by a significantly decreased WHR on frontal images (mean [standard error of the mean], 0.85 [0.05] vs 0.80 [0.05], P < .005) and a more projected buttocks indicated by a significant reduction in WHR on lateral images (0.92 [0.07] vs 0.87 [0.07], P < .0001). Among the patients who responded to the survey, 73% indicated that their waistline had aesthetically improved, 6.7% felt it had not changed, and 20% felt that it had worsened. An aesthetic improvement of the buttocks was reported by 53%, 40% felt their buttocks had not changed, and 6.7% felt their buttocks appearance had worsened. CONCLUSIONS: Bilateral LAP flap breast reconstruction leads to improved waistline definition and buttock projection, bringing patients closer to ideal aesthetic proportions. This reconstructive approach is ideal for patients who are not candidates for abdominal free flaps, but who demonstrate excess flank tissue and seek a more defined waistline and projected buttocks.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.

Robotics in Plastic Surgery: It's Here.

SUMMARY: Although robotic surgery has been routinely established in other surgical disciplines, robotic technologies have been less readily adopted in plastic surgery. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, most reconstructive procedures, including microsurgery, have continued to necessitate an open approach. Recent advances in robotics and artificial intelligence, however, are gaining momentum and have shown significant promise to improve patient care in plastic surgery. These next-generation surgical robots have the potential to enable surgeons to perform complex procedures with greater precision, flexibility, and control than previously possible with conventional techniques. Successful integration of robotic technologies into clinical practice in plastic surgery requires achieving key milestones, including implementing appropriate surgical education and garnering patient trust.

Acetylsalicylic Acid Is Not Associated With Improved Clinical Outcomes After Microsurgical Breast Reconstruction.

INTRODUCTION: Microvascular thrombosis with resultant flap loss remains a devastating complication in autologous breast reconstruction. While acetylsalicylic acid (ASA) for prevention of microvascular thrombosis is commonly administered postoperatively, clinical evidence supporting this practice remains insufficient. Here, we investigate the association of postoperative ASA administration with differences in clinical outcomes following microsurgical breast reconstruction. METHODS: A prospectively maintained database was queried to identify patients who had undergone microsurgical breast reconstruction. Patients were categorized based on whether they had received postoperative ASA for 30 d (Group 1) or had not received ASA (Group 2). Patient demographics, reconstructive outcomes, complications, and transfusion requirements were retrieved. RESULTS: One hundred thirty six patients with a mean age of 49.5 y and a mean body mass index of 28.5 kg/m2 who had undergone a total of 216 microsurgical breast reconstructions were included. No significant differences were noted with regard to patient demographics with the exceptions of increased rates of neoadjuvant chemotherapy and delayed reconstruction in Group 1. There were no significant differences in the rates of postoperative complications including breast hematoma, mastectomy skin flap necrosis, partial flap necrosis, seroma, and deep venous thrombosis between patients who did or did not receive ASA postoperatively. Similarly, no difference was noted regarding postoperative blood transfusion rates (Group 1: 9.9% versus Group 2: 9.1%; P = 0.78). Finally, patients in Group 1 had significantly longer hospital stays (Q1 = 4, median = 4.5, Q3 = 5). CONCLUSIONS: Postoperative ASA administration is not associated with improved postoperative clinical outcomes. The use of ASA routinely after autologous breast reconstruction does not appear to be a necessity in practice.

Blockchain, Information Security, Control, and Integrity: Who Is in Charge?

SUMMARY: Blockchain technology has attracted substantial interest in recent years, most notably for its effect on global economics through the advent of cryptocurrency. Within the health care domain, blockchain technology has been actively explored as a tool for improving personal health data management, medical device security, and clinical trial management. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, integration of blockchain technologies within plastic surgery is in its infancy. Recent advances and mainstream adoption of blockchain are gaining momentum and have shown significant promise for improving patient care and information management. In this article, the authors explain what defines a blockchain and discuss its history and potential applications in plastic surgery. Existing evidence suggests that blockchain can enable patient-centered data management, improve privacy, and provide additional safeguards against human error. Integration of blockchain technology into clinical practice requires further research and development to demonstrate its safety and efficacy for patients and providers.

Macrophage-mediated PDGF Activation Correlates With Regenerative Outcomes Following Musculoskeletal Trauma.

OBJECTIVE: Our objective was to identify macrophage subpopulations and gene signatures associated with regenerative or fibrotic healing across different musculoskeletal injury types. BACKGROUND: Subpopulations of macrophages are hypothesized to fine tune the immune response after damage, promoting either normal regenerative, or aberrant fibrotic healing. METHODS: Mouse single-cell RNA sequencing data before and after injury were assembled from models of musculoskeletal injury, including regenerative and fibrotic mouse volumetric muscle loss (VML), regenerative digit tip amputation, and fibrotic heterotopic ossification. R packages Harmony , MacSpectrum , and Seurat were used for data integration, analysis, and visualizations. RESULTS: There was a substantial overlap between macrophages from the regenerative VML (2 mm injury) and regenerative bone models, as well as a separate overlap between the fibrotic VML (3 mm injury) and fibrotic bone (heterotopic ossification) models. We identified 2 fibrotic-like (FL 1 and FL 2) along with 3 regenerative-like (RL 1, RL 2, and RL 3) subpopulations of macrophages, each of which was transcriptionally distinct. We found that regenerative and fibrotic conditions had similar compositions of proinflammatory and anti-inflammatory macrophages, suggesting that macrophage polarization state did not correlate with healing outcomes. Receptor/ligand analysis of macrophage-to-mesenchymal progenitor cell crosstalk showed enhanced transforming growth factor ß in fibrotic conditions and enhanced platelet-derived growth factor signaling in regenerative conditions. CONCLUSION: Characterization of macrophage subtypes could be used to predict fibrotic responses following injury and provide a therapeutic target to tune the healing microenvironment towards more regenerative conditions.

Multiplexed evaluation of mouse wound tissue using oligonucleotide barcoding with single-cell RNA sequencing.

Despite its rapidly increased availability for the study of complex tissue, single-cell RNA sequencing remains prohibitively expensive for large studies. Here, we present a protocol using oligonucleotide barcoding for the tagging and pooling of multiple samples from healing wounds, which are among the most challenging tissue types for this application. We describe steps to generate skin wounds in mice, followed by tissue harvest and oligonucleotide barcoding. This protocol is also applicable to other species including rats, pigs, and humans. For complete details on the use and execution of this protocol, please refer to Stoeckius et al. (2018),1 Galiano et al. (2004),2 and Mascharak et al. (2022).3.

Outcomes of Biosynthetic and Synthetic Mesh in Ventral Hernia Repair.

The introduction of mesh for reinforcement of ventral hernia repair (VHR) led to a significant reduction in hernia recurrence rates. However, it remains controversial whether synthetic or biologic mesh leads to superior outcomes. Recently, hybrid mesh consisting of reinforced biosynthetic ovine rumen (RBOR) has been developed and aims to combine the advantages of biologic and synthetic mesh; however, outcomes after VHR with RBOR have not yet been compared with the standard of care. Methods: We performed a retrospective analysis on 109 patients, who underwent VHR with RBOR (n = 50) or synthetic polypropylene mesh (n = 59). Demographic characteristics, comorbidities, postoperative complications, and recurrence rates were analyzed and compared between the groups. Multivariate logistic regression models were fit to assess associations of mesh type with overall complications and surgical site occurrence (SSO). Results: Patients who underwent VHR with RBOR were older (mean age 63.7 versus 58.8 years, P = 0.02) and had a higher rate of renal disease (28.0 versus 10.2%, P = 0.01) compared with patients with synthetic mesh. Despite an unfavorable risk profile, patients with RBOR had lower rates of SSO (16.0 versus 30.5%, P = 0.12) and similar hernia recurrence rates (4.0 versus 6.78%, P = 0.68) compared with patients with synthetic mesh. The use of synthetic mesh was significantly associated with higher odds for overall complications (3.78, P < 0.05) and SSO (3.87, P < 0.05). Conclusion: Compared with synthetic polypropylene mesh, the use of RBOR for VHR mitigates SSO while maintaining low hernia recurrence rates at 30-month follow-up.

Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.

Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.

Two Independent Capsules Surrounding a Single Textured Implant in Ehlers-Danlos Syndrome.

Textured breast implants are associated with prolonged inflammation leading to increased risk for complications such as the development of anaplastic large cell lymphoma. The underlying molecular mechanisms that drive increased inflammation toward textured implants (compared with smooth implants) remain poorly understood. Here, we present the first known case of a patient with Ehlers-Danlos syndrome (EDS) who developed two independent fibrotic capsules around a single textured silicone implant. The patient was found to have one internal capsule tightly adherent to the implant and a second external capsule that was attached to the surrounding tissue. We observed that the internal implant-adherent capsule was composed of a highly aligned and dense collagen network, completely atypical for EDS and indicative of a high mechanical stress environment. In contrast, the external nonadherent capsule, which primarily interacted with the smooth surface of the internal capsule, displayed disorganized collagen fibers with no discernible alignment, classic for EDS. Remarkably, we found that the internal capsule displayed high activation of monocyte chemoattractant protein-1, a mechanoresponsive inflammatory mediator that was not elevated in the disorganized external capsule. Taken together, these findings demonstrate that the tight adhesion between the textured implant surface and the internal capsule creates a high mechanical stress environment, which is responsible for the increased local inflammation observed in the internal capsule. This unique case demonstrates that mechanical stress is able to override genetic defects locally in collagen organization and directly connects the textured surface of implants to prolonged inflammation.

Combining Breast and Ovarian Operations Increases Complications.

BACKGROUND: Breast cancer resulting from a genetic mutations, such as BRCA1 or BRCA2, is seen in 5 to 10 percent of patients. More widespread genetic testing has increased the number of affected women undergoing prophylactic mastectomy and oophorectomy. Recent studies have yielded mixed results regarding complication rates after combined breast and ovarian operations. The authors compared surgical outcomes of breast operations performed in combination with salpingo-oophorectomies or as separate procedures. METHODS: The authors retrospectively analyzed surgical complications and length of hospital stay in 145 female patients, from which 87 had undergone combined breast surgery and salpingo-oophorectomy, and 58 had undergone these procedures separately. Multivariate logistic regression models were used to calculate odds ratios and 95 percent confidence intervals. RESULTS: Patients undergoing combined breast and ovarian operations experienced higher rates of overall complications (46.5 percent versus 19 percent; p < 0.001), infections (22.2 percent versus 8.6 percent; p < 0.05), and delayed wound healing (13.2 percent versus 0 percent; p < 0.05) related to the breast surgery, when compared with patients undergoing separate procedures. Multivariate logistic regression analysis confirmed a significant association between combined surgery and overall postoperative complications (OR, 5.87; 95 percent CI, 2.03 to 16.91; p = 0.02). Patients undergoing tissue expander-based breast reconstruction combined with ovarian surgery had significantly longer hospital stays compared to patients undergoing separate procedures (3.5 days versus 1.8 days; p < 0.001). CONCLUSIONS: The authors' data indicate that combining breast and ovarian operations is associated with a higher risk of postoperative complications related to the breast procedure and increases the duration of hospital stay in patients with tissue expander-based reconstructions. The authors' study provides valuable information for preoperative counseling of patients considering both breast and ovarian surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Regenerative Macrophage Polarization and Vascularization for Soft-Tissue Engineering.

BACKGROUND: Fractionated fat has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft-tissue defects is limited because of volume loss over time. The authors have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel composite enriched with fractionated fat. METHODS: Fractionated fat was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with nanofiber hydrogel composite (nanofiber hydrogel composite with fractionated fat). Nanofiber hydrogel composite with fractionated fat or nanofiber hydrogel composite alone was placed into isolation chambers together with arteriovenous loops, which were subcutaneously implanted into the groin of rats (n = 8 per group). After 21 days, animals were euthanized and systemically perfused with ink, and tissue was explanted for histologic analysis. Immunofluorescent staining and confocal laser scanning microscopy were used to quantify CD34+ progenitor cell and macrophage subpopulations. RESULTS: Nanofiber hydrogel composite with fractionated fat tissue maintained its shape without shrinking and showed a significantly stronger functional vascularization compared to composite alone after 21 days of implantation (mean vessel count, 833.5 ± 206.1 versus 296.5 ± 114.1; p = 0.04). Tissue heterogeneity and cell count were greater in composite with fractionated fat (mean cell count, 49,707 ± 18,491 versus 9263 ± 3790; p = 0.005), with a significantly higher number of progenitor cells and regenerative CD163+ macrophages compared to composite alone. CONCLUSIONS: Fractionated fat-enriched nanofiber hydrogel composite transforms into highly vascularized soft tissue over 21 days without signs of shrinking and promotes macrophage polarization toward regenerative phenotypes. Enrichment of injectable nanofiber hydrogel composite with fractionated fat represents a promising approach for durable reconstruction of soft-tissue defects. CLINICAL RELEVANCE STATEMENT: The authors' approach for tissue engineering may ultimately lay the groundwork for clinically relevant applications with the goal of generating large volumes of vascularized soft tissue for defect reconstruction without donor site morbidity.

Reinforced Biologic Mesh Reduces Postoperative Complications Compared to Biologic Mesh after Ventral Hernia Repair.

BACKGROUND: The use of biologic mesh to reinforce the abdominal wall in ventral hernia repair has been proposed as a viable alternative to synthetic mesh, particularly for high-risk patients and in contaminated settings. However, a comparison of clinical outcomes between the currently available biologic mesh types has yet to be performed. METHODS: We performed a retrospective analysis of 141 patients who had undergone ventral hernia repair with biologic mesh, including noncross-linked porcine ADM (NC-PADM) (n = 51), cross-linked porcine ADM (C-PADM) (n = 17), reinforced biologic ovine rumen (RBOR) (n = 36), and bovine ADM (BADM) (n = 37) at the Stanford University Medical Center between 2002 and 2020. Postoperative donor site complications and rates of hernia recurrence were compared between patients with different biologic mesh types. RESULTS: Abdominal complications occurred in 47.1% of patients with NC-PADM, 52.9% of patients with C-PADM, 16.7% of patients with RBOR, and 43.2% of patients with BADM (P = 0.015). Relative risk for overall complications was higher in patients who had received NC-PADM (RR = 2.64, P = 0.0182), C-PADM (RR = 3.19, P = 0.0127), and BADM (RR = 2.11, P = 0.0773) compared with those who had received RBOR. Furthermore, relative risk for hernia recurrence was also higher in all other mesh types compared with RBOR. CONCLUSION: Our data indicate that RBOR decreases abdominal complications and recurrence rates after ventral hernia repair compared with NC-PADM, C-PADM, and BADM.

Inhibiting Fibroblast Mechanotransduction Modulates Severity of Idiopathic Pulmonary Fibrosis.

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that affects 63 in every 100,000 Americans. Its etiology remains unknown, although inflammatory pathways appear to be important. Given the dynamic environment of the lung, we examined the significance of mechanotransduction on both inflammatory and fibrotic signaling during IPF. Innovation: Mechanotransduction pathways have not been thoroughly examined in the context of lung disease, and pharmacologic approaches for IPF do not currently target these pathways. The interplay between mechanical strain and inflammation in pulmonary fibrosis remains incompletely understood. Approach: In this study, we used conditional KO mice to block mechanotransduction by knocking out Focal Adhesion Kinase (FAK) expression in fibroblasts, followed by induction of pulmonary fibrosis using bleomycin. We examined both normal human and human IPF fibroblasts and used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western Blot to evaluate the effects of FAK inhibitor (FAK-I) on modulating fibrotic and inflammatory genes. Results: Our data indicate that the deletion of FAK in mice reduces expression of fibrotic and inflammatory genes in lungs. Similarly, mechanical straining in normal human lung fibroblasts activates inflammatory and fibrotic pathways. The FAK inhibition decreases these signals but has a less effect on IPF fibroblasts as compared with normal human fibroblasts. Conclusion: Administering FAK-I at early stages of fibrosis may attenuate the FAK-mediated fibrotic response pathway in IPF, potentially mediating disease progression.

The Plane of Mesh Placement Does Not Impact Abdominal Donor Site Complications in Microsurgical Breast Reconstruction.

BACKGROUND: Reinforcement of the abdominal wall with synthetic mesh in autologous breast reconstruction using abdominal free tissue transfer decreases the risk of bulging and herniation. However, the impact of the plane of mesh placement on donor site complications has not yet been investigated. METHODS: We performed a retrospective analysis of 312 patients who had undergone autologous breast reconstruction with muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps or deep inferior epigastric perforator (DIEP) flaps as well as polypropylene mesh implantation at the donor site. Donor site complications were compared among patients with different flap types and different mesh positions including overlay (n = 90), inlay and overlay (I-O; n = 134), and sublay (n = 88). RESULTS: Abdominal hernias occurred in 2.86% of patients who had undergone MS-TRAM reconstructions and in 2.63% of patients who had undergone DIEP reconstructions. When comparing patients with different mesh positions, donor site complications occurred in 14.4% of patients with overlay mesh, 13.4% of patients with I-O mesh, and 10.2% of patients with sublay mesh (P = 0.68). Abdominal hernias occurred in 4.44% of patients with overlay mesh, 2.24% of patients with I-O mesh, and 2.27% of patients with sublay mesh (P = 0.69). Multivariable logistic regression analysis did not identify a significant association between mesh position and hernia rates as well as wound complications. CONCLUSIONS: Our data indicate that the plane of synthetic mesh placement in relation to the rectus abdominis muscle does not impact the rate of postoperative donor site complications in patients undergoing breast reconstruction with MS-TRAM or DIEP flaps.

Advances in Tissue Expander Technology Enable Early Targeted Intervention in Prepectoral Breast Reconstruction.

Seroma and infection are among the most common complications after staged prepectoral implant-based reconstruction. Advances in tissue expander technology permit seroma aspiration via an integrated drain port, thus, holding promise for improving clinical outcomes. METHODS: A prospectively maintained database of patients who had undergone immediate prepectoral breast reconstruction using the Sientra AlloX2 tissue expander was used to determine the rate of postoperative seroma formation, its volume and microbiological spectrum, as well as postoperative complications. RESULTS: 49 patients (mean age: 49 years, mean body mass index: 24.5 kg/m2) underwent 79 prepectoral breast reconstructions. Seroma was clinically suspected in 26 reconstructions (32.9%) and was easily aspirated in all cases via the integrated drain port. Importantly, periprosthetic fluid was successfully aspirated in 45 reconstructions (57%) without any clinical evidence for seroma, with aspirated cumulative fluid volumes exceeding 10 cm3 in 12 reconstructions. Bacterial cultures from aspirated fluid were positive in six patients (12.2%), of whom two developed clinical signs of infection, at which point targeted antibiotic treatment was initiated. CONCLUSIONS: Our study demonstrates that routine office-based aspiration of periprosthetic fluid via the integrated drain port of the AlloX2 tissue expander not only permits successful aspiration of periprosthetic fluid but also allows aspirated fluid to be sent for culture, thus, providing a lead-time advantage for initiation of targeted antibiotic therapy in cases of postoperative surgical site infection. Furthermore, our observations indicate that positive bacterial cultures in the absence of clinical signs of infection do not mandate antibiotic therapy.

Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing.

Cutaneous wounds are a growing global health burden as a result of an aging population coupled with increasing incidence of diabetes, obesity, and cancer. Cell-based approaches have been used to treat wounds due to their secretory, immunomodulatory, and regenerative effects, and recent studies have highlighted that delivery of stem cells may provide the most benefits. Delivering these cells to wounds with direct injection has been associated with low viability, transient retention, and overall poor efficacy. The use of bioactive scaffolds provides a promising method to improve cell therapy delivery. Specifically, hydrogels provide a physiologic microenvironment for transplanted cells, including mechanical support and protection from native immune cells, and cell-hydrogel interactions may be tailored based on specific tissue properties. In this review, we describe the current and future directions of various cell therapies and usage of hydrogels to deliver these cells for wound healing applications.

Adipose-Derived Stromal Cells Seeded in Pullulan-Collagen Hydrogels Improve Healing in Murine Burns.

Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known proangiogenic and immunomodulatory paracrine effects. Our laboratory has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their proangiogenic capacity in vivo. Concurrently, recent research suggests that prospective isolation of cell subpopulations with desirable transcriptional profiles can be used to further improve cell-based therapies. In this study, we examined whether adipose-derived stem cell (ASC)-seeded hydrogels could improve wound healing following thermal injury using a murine contact burn model. Partial thickness contact burns were created on the dorsum of mice. On days 5 and 10 following injury, burns were debrided and received either ASC hydrogel, ASC injection alone, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis. This experiment was repeated using CD26+/CD55+ FACS-enriched ASCs to further evaluate the regenerative potential of ASCs in wound healing. ASC hydrogel-treated burns demonstrated accelerated time to reepithelialization, greater vascularity, and increased expression of the proangiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the profibrotic gene Timp1 and proinflammatory gene Tnfa was downregulated in ASC hydrogel-treated burns. ASC hydrogel-treated burns exhibited reduced scar area compared to hydrogel-treated and control wounds, with equivalent scar density. CD26+/CD55+ ASC hydrogel treatment resulted in accelerated healing, increased dermal appendage count, and improved scar quality with a more reticular collagen pattern. Here we find that ASC hydrogel therapy is effective for treating burns, with demonstrated proangiogenic, fibromodulatory, and immunomodulatory effects. Enrichment for CD26+/CD55+ ASCs has additive benefits for tissue architecture and collagen remodeling postburn injury. Research is ongoing to further facilitate clinical translation of this promising therapeutic approach. Impact statement Burns remain a significant public health burden. Stem cell therapy has gained attention as a promising approach for treating burns. We have developed a pullulan-collagen biomimetic hydrogel scaffold that can be seeded with adipose-derived stem cells (ASCs). We assessed the delivery and activity of our scaffold in a murine contact burn model. Our results suggest that localized delivery of ASC hydrogel treatment is a promising approach for the treatment of burn wounds, with the potential for rapid clinical translation. We believe our work will have broad implications for both hydrogel therapeutics and regenerative medicine and will be of interest to the general scientific community.