Comprehensive Reconstructive Care for Patients of All Gender Identities After Cancer of the Breast.

ABSTRACT: Breast cancer can affect anyone; therefore, it affects people of all gender identities. Reconstructive options after breast cancer must then address the needs of all people. Our institution is unique in its provision of both high-level comprehensive breast and gender affirmation care. In our practice, patients have expressed gender diverse identities during their breast cancer reconstructive journey. In these cases, goals have deviated from traditional breast restoration, gravitating toward gender-affirming mastectomy, or results often seen with "top surgery." We present a framework for the administration of breast cancer care and discussions of reconstruction from a lens of gender inclusivity. Breast cancer is a diagnosis that has been gendered, resulting in the erasure and exclusion of reconstructive needs for people affected by breast cancer that are not cisgender women. This is illustrated through the case of a nonbinary individual seen in breast cancer clinic for multifocal ductal carcinoma in situ. Our standard review of options of "going flat," implant-based reconstruction, and autologous reconstruction led to initial confusion given their early exploration of gender identity co-occurring with a new diagnosis of breast cancer. These scenarios can be challenging when viewed solely from the perspective of a breast reconstructive surgeon or a gender-affirming surgeon alone. Both perspectives are often needed. Our gender-affirming and breast reconstructive teams have discussed methods to identify patients who require more robust discussion of gender identity and reconstructive options in the setting of breast cancer, such as chest masculinization. By adding gender-affirming surgeons to the list of providers available to counsel breast cancer patients, we may be able to better provide early education on all reconstructive options and appropriately address the needs of transgender and gender diverse people affected by breast cancer.

Evaluation of a Plastic and Reconstructive Surgery Resident Non-surgical Cosmetic Clinic Experience.

INTRODUCTION: An important component of plastic surgery residency training is independent cosmetic patient management. A resident cosmetic clinic was created at Oregon Health & Science University in 2007 to expand this experience. The cosmetic clinic has traditionally been most successful in offering nonsurgical facial rejuvenation with neuromodulators and soft tissue fillers. This study focuses on the demographics of the patient population and the treatments provided over a 5-year period and compares this experience to those of the same program's attending cosmetic clinics. METHODS: A retrospective chart review of all patients seen at Oregon Health & Science University's Plastic and Reconstructive Surgery Resident Cosmetic Clinic between January 1, 2017, and December 31, 2021 was performed. Patient demographics, type of injectable received (neuromodulator versus soft tissue filler), location of injection, and additional cosmetic procedures were evaluated. RESULTS: Two hundred patients met the study criteria, which included 114 seen in the resident clinic (RC), 31 seen in attending clinic (AC), and 55 patients seen in both. A primary analysis compared the two groups seen in the resident and attending only clinics. The average age of patients seen in the RC was younger, 45 versus 51.5 (P ≤ 0.05). There was a trend toward more patients in the RC being involved in healthcare as compared to those patients seen in the AC, but this difference was not found to be statistically significant. The median number of neuromodulator visits in the RC was 2 (1, 4) versus 1 (1, 2) in the AC (P ≤ 0.05) The most common location for neuromodulator injections in both clinics was the corrugators. CONCLUSIONS: Patients in the resident cosmetic clinic were younger females, most receiving neuromodulator injections. No statistically significant differences were identified in patient population, injections received, and location of injections between the two clinics, indicating a similar trainee skill set and patient care plan between the two clinics.

Evaluating the Importance of Sub-Internships on the 2022 Integrated Plastic Surgery Match During Continued COVID-19 Regulations.

OBJECTIVE: Following the 2021 integrated plastic surgery match, we found a significant increase in home match rates and decrease in match rate for students without a home plastic surgery program with the elimination of visiting sub-internships and the initiation of virtual interviewing. With the return of visiting sub-internships in the 2022 match cycle, we hypothesize that these rates will approach values more consistent with historical controls. DESIGN: Program match data was obtained from posts to residency program Instagram pages and posts associated with the hashtag #PRSMatch2022. Data on visiting sub-internship matches was obtained from a publicly available Google Sheet with applicant contributors. The Chi square test was used to assess for differences. SETTING: Medical schools and plastic surgery programs were categorized into west, midwest, south, and northeast regions. PARTICIPANTS: Matched applicants to integrated plastic surgery residency programs. RESULTS: In total, 192 of 194 (99%) of applicants matched to integrated plastic surgery residency positions were identified. The match rate for applicants without an affiliated plastic surgery program (31.3%) increased from 2021 (p = 0.03) and returned to a level consistent with historical controls (p = 0.38). Similarly, the home program match rate (15.1%) and match rate for applicants from Top 40 medical schools (34.2%) decreased from 2021, returning to pre-pandemic levels (p = 0.63, p = 0.12). Finally, regional match preferences remained generally consistent with historical controls, apart from a higher proportion of northeast applicants matching to programs in the northeast (72.5%, p = 0.04), and a lower proportion of west applicants matching to programs in the west (26.3%, p = 0.002). CONCLUSIONS: The 2022 integrated plastic surgery match cycle saw a reversal of many of the changes to match rates seen in the 2021 cycle. These changes may be due to the reintroduction of visiting sub-internships following updates in COVID-19 policies.

Effect of COVID-19 Restrictions on 2021 Integrated Plastic Surgery Match Outcomes.

OBJECTIVE: Due to the Coronavirus Disease 2019 Pandemic (COVID-19), guidelines regarding both elimination of visiting subinternships and substitution of virtual interviews for the 2021 match were adopted. We hypothesize that these changes will result in an increase in home institution match rates compared to previous years. DESIGN: Program match data was obtained using information posted to residency program Instagram pages and the hashtag #PRSMatch2021. Chi square was used to assess differences between groups. SETTING: Medical school regions were categorized as West, Midwest, South, and Northeast and compared to match program region. PARTICIPANTS: Matched candidates to integrated plastic surgery residencies RESULTS: A total of 181/187 (96.8%) integrated plastic surgery matched candidates were identified. Compared to historical controls, there was a statistically significant increase in the home match rate (24.3%, p = 0.004) and statistically significant decrease in match rate for students without a home plastic surgery program (21.0%, p = 0.004). Similar to prior years, applicants were more likely to match in their own region for all regions (p < 0.001); however, there was a statistical increase in students staying in the South region for residency compared to previous years (p = 0.007). CONCLUSIONS: The 2021 match cycle resulted in an increase in home program match rates, while decreasing match rates among students without a home plastic surgery program. COVID-19 polices may have resulted in disadvantages to students from diverse institutional backgrounds. Influences of virtual subinternships and virtual interviews should be further evaluated.

Lymphatic and Mixed Malformations.

Lymphatic and mixed malformations are rare and variable in presentation. They arise due to errors in vascular and lymphatic formation during early embryonic development. This leads to persistent infiltration of lymph fluid into soft tissues and causes a locally invasive mass with pathologic sequelae. Departing from historically descriptive terminology, such as "cystic hygroma," lymphatic malformations are now categorized as macrocystic, microcystic, or mixed lesions, based on size. Advances in imaging modalities, such as ultrasonography and magnetic resonance imaging, have made accurate characterization of these lesions possible and ultimately allow for early diagnosis and implementation of appropriate treatment based on the morphology of the lymphatic malformation. Management of lymphatic malformations can be quite challenging, and a multidisciplinary approach is most effective for optimum aesthetic and functional outcomes. New discoveries in the molecular biology of lymphatic malformations have provided treatment targets and established a role for pharmacotherapy. Sclerotherapy, laser, and radiofrequency ablation have all proven to be effective as minimally invasive treatment options for lymphatic malformations. Surgical intervention has a role in the treatment of focal lesions recalcitrant to these less invasive techniques. Operative planning is dictated by clinical goals, size, anatomic location, characteristics, and extent of infiltration.

Pyoderma gangrenosum underrepresentation in non-dermatological literature.

BACKGROUND: Pyoderma gangrenosum (PG) is a chronic, ulcerative neutrophilic dermatosis. PG presents a diagnostic challenge, largely due to the many mimicking diseases, the lack of confirmatory laboratory or biological markers, and the absence of widely accepted diagnostic criteria. In particular, PG is often mistaken for necrotizing soft tissue infections (NSTI). METHODS: We reviewed four major textbooks each in general surgery, plastic surgery, trauma surgery, vascular surgery, emergency medicine, and dermatology. We also performed a search of review articles addressing NSTI and necrotizing fasciitis (NF). RESULTS: Ten out of the 20 non-dermatology textbooks did not list PG anywhere, and only two listed a differential diagnosis for PG. None of the non-dermatology textbooks indicated PG in the NSTI differential diagnosis, while three of the dermatology textbooks included PG in the NSTI differential diagnosis. PG was listed in all of the dermatology textbooks. Only one of the NSTI and NF articles mentioned PG in the differential diagnosis. CONCLUSIONS: There is an underrepresentation in major textbooks of surgery and emergency medicine and in NSTI and NF review articles when it comes to diagnosing PG. This might be leading to trainees and advanced providers in these fields being uninstructed on PG, and likely contributes to PG misdiagnosis and mismanagement. We recommend PG be included in the differential diagnosis of chronic ulcers and NSTI in non-dermatology textbooks. We also suggest adding identification and diagnosis of inflammatory mimickers of NSTI (e.g. PG) in teaching modules in surgical and emergency specialties to address this knowledge gap.

Differences in Chest Measurements between the Cis-female and Trans-female Chest Exposed to Estrogen and Its Implications for Breast Augmentation.

BACKGROUND: Gender confirming primary breast augmentation is becoming more common. The purpose of this study was to compare the demographic and anatomical differences in cis-female and trans-female populations. METHODS: This was a retrospective analysis of trans-female patients and cis-female patients undergoing primary breast augmentation at a single institution. Analysis included patient demographics and preoperative chest measurements including sternal notch to nipple distance (SSN), breast width (BW), nipple to inframammary fold distance (N-IMF), and nipple to midline distance (N-M). Continuous variables were compared using independent t tests, and discrete variables were compared using Pearson's χ2 tests. RESULTS: Eighty-two trans-female and 188 cis-female patients undergoing primary breast augmentation were included. Trans-female patients were older (40.37 versus 34.07), more likely to have psychological comorbidities (50% versus 12.23%), and had a higher body mass index, 27.46 kg/m2 versus 22.88 kg/m2 (P = 1.91E-07), than cis-female patients. Cis-female patients most commonly had an ectomorph body habitus (52% versus 26%), whereas trans-female patients most commonly had an endomorph body habitus (40% versus 7%). Pseudoptosis or ptosis was more commonly seen in cis-female patients (P = 0.0056). There were significant differences in preoperative breast measurements including sternal notch to nipple distance, BW, and N-M between groups, but not in N-IMF. The ratio of BW/N-IMF was statistically significant (P = 2.65E-07 on right), indicating that the similarity in N-IMF distance did not adjust for the difference in BW. CONCLUSIONS: The trans-female and cis-female populations seeking primary breast augmentation have significant demographic and anatomical differences. This has implications for surgical decision-making and planning to optimize outcomes for trans-female patients.

PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.

BACKGROUND: Cell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing. METHODS: Mesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics. RESULTS: PHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p < 0.05). Human umbilical vein endothelial cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p < 0.05). Wounds treated with PHD-2 knockdown mesenchymal stromal cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p < 0.05). Histologic studies revealed increased blood vessel density and increased cellularity in the wounds treated with PHD-2 knockdown mesenchymal stromal cells (p < 0.05). CONCLUSIONS: Silencing PHD-2 in mesenchymal stromal cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family transcription factors and up-regulation of multiple downstream angiogenic factors.

Age at the Time of Surgery and Maintenance of Head Size in Nonsyndromic Sagittal Craniosynostosis.

BACKGROUND: Repair of nonsyndromic sagittal craniosynostosis should durably improve intracranial volume and cranial index. The optimal timing of surgery is not known. The authors previously reported reoperation in patients aged younger than 6 months at primary repair. METHODS: Patients undergoing primary reconstruction for sagittal craniosynostosis before age 1 year between 2005 and 2013 at Oregon Health & Science University underwent retrospective computed tomographic determination of cranial index and intracranial volume preoperatively and 2 years postoperatively and head circumference measurements until age 6 years. RESULTS: Fifty-six patients undergoing operation before their first birthday were studied in two groups: those younger than 6 months [34 (61 percent)] and those aged 6 months or older at the time of operation. Head circumference percentile increased immediately after surgery but decreased at 1 and 2 years after surgery, significantly more so in patients younger than 6 months (p < 0.015 at 1 year; p < 0.011 at 2-year follow-up). Mean 2-year postoperative cranial index was significantly increased in both groups (p < 0.001), which did not differ preoperatively (younger than 6 months, 76.5; 6 months or older, 78.0) or 2 years postoperatively (younger than 6 months, 88.4; 6 months or older, 87.1; p = not significant). Intracranial volume increased in all patients from before surgery to 2 years postoperatively and was higher in the patients aged 6 months or older (p < 0.001). CONCLUSION: Cranial reconstruction for nonsyndromic sagittal craniosynostosis improved cranial index equally in all patients but increased head circumference and intracranial volume significantly more in patients who underwent surgical reconstruction at age 6 months or older. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Local Wound Care for Primary Cleft Lip Repair: Treatment and Outcomes With use of Topical Hydrogen Peroxide.

OBJECTIVES: This study highlights and validates a peroxide-based wound healing strategy for treatment of surgically closed facial wounds in a pediatric population. The authors identified pediatric patients undergoing primary cleft lip repair as a specific population to evaluate the outcomes of such a protocol. Through analysis of defined outcome measures, a reliable and reproducible protocol for postoperative wound care following primary cleft lip repair with favorable results is described. METHODS: This retrospective study analyzes wound healing outcomes in pediatric patients undergoing primary cleft lip repair from 2006 to 2011 at a tertiary academic center. The wound healing protocol was used in both primary unilateral and bilateral repairs. One hundred fortysix patients between the ages of 0 and 4 years underwent primary cleft lip repair and cleft rhinoplasty by a single, fellowship-trained craniofacial surgeon. Postoperatively, wounds were treated with half-strength hydrogen peroxide and bacitracin, as well as scar massage. Incisional dehiscence, hypertrophic scar formation, discoloration, infection, and reoperation were studied. Outcomes were evaluated in light of parent compliance, demographics, preoperative nasoalveolar molding (PNAM), and diagnosis. RESULTS: The authors identified 146 patients for inclusion in this study. There was no wound or incisional dehiscence. One hundred twenty-four patients demonstrated favorable cosmetic outcome. Only 3 (2%) of patients who developed suboptimal outcomes underwent secondary surgical revision (> 1 year after surgery). Demographic differences were not statistically significant, and PNAM treatment did not influence outcomes. CONCLUSION: These data validate the use of halfstrength hydrogen peroxide and bacitracin as part of a wound healing strategy in pediatric incisional wounds. The use of hydrogen peroxide produced comparable outcomes to previously published studies utilizing other wound healing strategies and, therefore, these study findings support the further use of this regimen for this particular population.

Epidermal or dermal specific knockout of PHD-2 enhances wound healing and minimizes ischemic injury.

INTRODUCTION: Hypoxia-inducible factor (HIF)-1α, part of the heterodimeric transcription factor that mediates the cellular response to hypoxia, is critical for the expression of multiple angiogenic growth factors, cell motility, and the recruitment of endothelial progenitor cells. Inhibition of the oxygen-dependent negative regulator of HIF-1α, prolyl hydroxylase domain-2 (PHD-2), leads to increased HIF-1α and mimics various cellular and physiological responses to hypoxia. The roles of PHD-2 in the epidermis and dermis have not been clearly defined in wound healing. METHODS: Epidermal and dermal specific PHD-2 knockout (KO) mice were developed in a C57BL/6J (wild type) background by crossing homozygous floxed PHD-2 mice with heterozygous K14-Cre mice and heterozygous Col1A2-Cre-ER mice to get homozygous floxed PHD-2/heterozygous K14-Cre and homozygous floxed PHD-2/heterozygous floxed Col1A2-Cre-ER mice, respectively. Ten to twelve-week-old PHD-2 KO and wild type (WT) mice were subjected to wounding and ischemic pedicle flap model. The amount of healing was grossly quantified with ImageJ software. Western blot and qRT-PCR was run on protein and RNA from primary cells cultured in vitro. RESULTS: qRT-PCR demonstrated a significant decrease of PHD-2 in keratinocytes and fibroblasts derived from tissue specific KO mice relative to control mice (*p<0.05). Western blot analysis showed a significant increase in HIF-1α and VEGF protein levels in PHD-2 KO mice relative to control mice (*p<0.05). PHD-2 KO mice showed significantly accelerated wound closure relative to WT (*p<0.05). When ischemia was analyzed at day nine post-surgery in a flap model, the PHD-2 tissue specific knockout mice showed significantly more viable flaps than WT (*p<0.05). CONCLUSIONS: PHD-2 plays a significant role in the rates of wound healing and response to ischemic insult in mice. Further exploration shows PHD-2 KO increases cellular levels of HIF-1α and this increase leads to the transcription of downstream angiogenic factors such as VEGF.

Adult stem cells in small animal wound healing models.

This chapter broadly reviews the use of stem cells as a means to accelerate wound healing, focusing first on the properties of stem cells that make them attractive agents to influence repair, both alone and as vehicles for growth factor delivery. Major stem cell reservoirs are described, including adult, embryonic, and induced pluripotent cell sources, outlining the advantages and limitations of each source as wound healing agents, as well as the possible mechanisms responsible for wound healing acceleration. Finally, the chapter includes a materials and methods section that provides an in-depth description of adult tissue harvest techniques.

Evidence that mast cells are not required for healing of splinted cutaneous excisional wounds in mice.

Wound healing is a complex biological process involving the interaction of many cell types to replace lost or damaged tissue. Although the biology of wound healing has been extensively investigated, few studies have focused on the role of mast cells. In this study, we investigated the possible role of mast cells in wound healing by analyzing aspects of cutaneous excisional wound healing in three types of genetically mast cell-deficient mice. We found that C57BL/6-Kit(W-sh/W-sh), WBB6F1-Kit(W/W-v), and Cpa3-Cre; Mcl-1(fl/fl) mice re-epithelialized splinted excisional skin wounds at rates very similar to those in the corresponding wild type or control mice. Furthermore, at the time of closure, scars were similar in the genetically mast cell-deficient mice and the corresponding wild type or control mice in both quantity of collagen deposition and maturity of collagen fibers, as evaluated by Masson's Trichrome and Picro-Sirius red staining. These data indicate that mast cells do not play a significant non-redundant role in these features of the healing of splinted full thickness excisional cutaneous wounds in mice.

Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing.

Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds.

Adipose-derived stromal cells overexpressing vascular endothelial growth factor accelerate mouse excisional wound healing.

Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (ß-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a commercially available transfection reagent, were included as controls. ASCs transfected using PBAEs showed enhanced transfection efficiency and 12-15-fold higher VEGF production compared with cells transfected using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated wound healing, with full wound closure observed at 8 days compared to 10-12 days in groups treated with ASCs alone or saline control (*P < 0.05). Histology and polarized microscopy showed increased collagen deposition and more mature collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs than ASCs alone. Our results demonstrate the efficacy of using nonviral-engineered ASCs to accelerate wound healing, which may provide an alternative therapy for treating many diseases in which wound healing is impaired.

Scarless fetal skin wound healing update.

Scar formation, a physiologic process in adult wound healing, can have devastating effects for patients; a multitude of pathologic outcomes, affecting all organ systems, stems from an amplification of this process. In contrast to adult wound repair, the early-gestation fetal skin wound heals without scar formation, a phenomenon that appears to be intrinsic to fetal skin. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to this scarless repair. Despite the great increase in knowledge gained over the past decades, the precise mechanisms regulating scarless fetal healing remain unknown. Herein, we describe the current proposed mechanisms underlying fetal scarless wound healing in an effort to recapitulate the fetal phenotype in the postnatal environment.

Enhancement of human adipose-derived stromal cell angiogenesis through knockdown of a BMP-2 inhibitor.

BACKGROUND: Previous studies have demonstrated the role of noggin, a bone morphogenetic protein-2 inhibitor, in vascular development and angiogenesis. The authors hypothesized that noggin suppression in human adipose-derived stromal cells would enhance vascular endothelial growth factor secretion and angiogenesis in vitro and in vivo to a greater extent than bone morphogenetic protein-2 alone. METHODS: Human adipose-derived stromal cells were isolated from human lipoaspirate (n = 6) noggin was knocked down using lentiviral techniques. Knockdown was confirmed and angiogenesis was assessed by tubule formation and quantitative real-time polymerase chain reaction. Cells were seeded onto scaffolds and implanted into a 4-mm critical size calvarial defect. In vivo angiogenic signaling was assessed by immunofluorescence and immunohistochemistry. RESULTS: Human adipose-derived stromal cells with noggin suppression secreted significantly higher amounts of angiogenic proteins, expressed higher levels of angiogenic genes, and formed more tubules in vitro. In vivo, calvarial defects seeded with noggin shRNA human adipose-derived stromal cells exhibited a significantly higher number of vessels in the defect site than controls by immunohistochemistry (p < 0.05). In addition, bone morphogenetic protein-2-releasing scaffolds significantly enhanced vascular signaling in the defect site. CONCLUSIONS: Human adipose-derived stromal cells demonstrate significant increases in angiogenesis in vitro and in vivo with both noggin suppression and BMP-2 supplementation. By creating a cell with noggin suppressed and by using a scaffold with increased bone morphogenetic protein-2 signaling, a more angiogenic niche can be created.

Antimycotic ciclopirox olamine in the diabetic environment promotes angiogenesis and enhances wound healing.

Diabetic wounds remain a major medical challenge with often disappointing outcomes despite the best available care. An impaired response to tissue hypoxia and insufficient angiogenesis are major factors responsible for poor healing in diabetic wounds. Here we show that the antimycotic drug ciclopirox olamine (CPX) can induce therapeutic angiogenesis in diabetic wounds. Treatment with CPX in vitro led to upregulation of multiple angiogenic genes and increased availability of HIF-1α. Using an excisional wound splinting model in diabetic mice, we showed that serial topical treatment with CPX enhanced wound healing compared to vehicle control treatment, with significantly accelerated wound closure, increased angiogenesis, and increased dermal cellularity. These findings offer a promising new topical pharmacologic therapy for the treatment of diabetic wounds.