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Background:. Although long-term benefits of reduction mammaplasty have been proven, the appropriate age for adolescent reduction mammaplasty has been highly debated due to possible need for revision surgery. Practitioners often delay offering breast reduction to adolescents below age 18 based on presumed insurance denial. We reviewed trends in insurance denial at a single children’s hospital to analyze whether age and/or insurance carriers have a significant impact on coverage of breast reduction. Methods:. A retrospective chart review from 2012 to 2022 of cisgender female patients with macromastia aged 12–20 years at the time of diagnosis was analyzed for differences in breast reduction insurance coverage based on age and body mass index at the time of diagnosis, referral to plastic surgery, and surgery. Results:. A total of 121 cisgender women were included. There were no significant differences in the mean ages of patients who underwent breast reduction versus those who did not (16.46 years versus 16.96 years, respectively; P = 0.089), or in the mean body mass index for patients who did versus those who did not receive breast reduction (28.58 kg/m² versus 29.05kg/m², P = 0.382). Furthermore, there were no significant differences in the proportion of patients undergoing breast reduction by age (P = 0.200) or by insurance class (P = 0.403). Conclusion:. Although insurance varies with carrier, the present findings suggest that surgeons need not delay in facilitating preauthorization for breast reduction in symptomatic patients presenting anytime during their teenage years.

Background:. Although career choices are often shaped by training and mentors, it is not clear how training backgrounds have influenced whether plastic surgeons pursue leadership positions. Analysis of these training pathways can serve as a key component of career planning for future leaders. Methods:. The American Board of Plastic Surgery’s annual Newsletter to Diplomates was used to collate surgeons receiving board certification between 2002 and 2013. Online public profiles were used to collect training background data about each surgeon, including fellowship training, board certification year, MBA degree, otolaryngology or maxillofacial surgery training before commencing plastic surgery training, and leadership positions in surgery. A logistic multinomial regression was used to test the effect of training backgrounds on different types of leadership positions. Results:. In total, 2190 plastic surgeons were included in the analysis. Factors increasing the probability of holding any type of position included fellowships in microsurgery, craniofacial, and hand; an international fellowship; multiple fellowships; a fellowship not otherwise specified; and MBA degree. Training background factors affected probabilities differently for each of the studied positions including chair/chief, vice chair/vice chief, program director, plastic surgery medical director, other institutional positions, and national society positions. Conclusions:. Training backgrounds of plastic surgeons in leadership positions are multifaceted, involving a mix of intrinsic and extrinsic factors such as additional educational pursuits, subspecialty training, duration of practice, and practice setting. This analysis can help direct current trainees who aspire to future leadership in plastic surgery.

Objective: This study aims to investigate potential differences in surgical subspecialty match rates between medical schools with and without elective rotations in the respective surgical subspecialties. Design: Data on duration of surgical rotations were retrieved from each school's public website. Fisher exact tests were performed to identify any statistically significant differences in surgical specialty match rates by allopathic versus osteopathic and elective clinical exposure. A linear regression was performed to determine the correlation between number of surgical electives offered and proportion of students matching in any surgical subspecialty. Results: The number of surgical electives offered by allopathic medical schools positively correlated with the proportion of students matching in any surgical specialty (R2 = 0.038, p = 0.018). Elective rotations in surgical subspecialties were associated with higher match rates in ophthalmology (OR 1.864, 95 % CI 1.196, 3.059, p

Background:. Evaluation of practice patterns by American Board of Plastic Surgery (ABPS) diplomates allows for a greater understanding as to how the field is progressing. Understanding evolving procedural trends can give insight into plastic surgeons’ subspecialty focus and influence resident training to prepare them for future practice. Methods:. American Society of Plastic Surgeons member only projections for aesthetic and reconstructive procedures were reviewed from 1999 to 2018 in 5-year increments to identify shifts in frequency between the beginning (1999–2003) and end (2014–2018) of the timeframe. Tracer utilization for all four ABPS modules were also examined between 2014 and 2018. Descriptive statistics were performed to identify significant changes (P < 0.05) in subspecialty focus and procedure trends. Results:. Annual procedure incidence between 2014 and 2018 was compared with that between 1999 and 2003. The annual number of procedures more than doubled from 3,244,084 to 6,628,082. Among reconstructive procedures, there was a statistically significant increase in the number of breast reconstruction, breast implant removal, and maxillofacial surgery procedures, and a statistically significant decrease in the number of procedures focused on reconstruction of birth defects, burn injuries, and hand anomalies. In aesthetic surgery, significant increases were seen in the number of augmentation mammoplasty, abdominoplasty, and mastopexy procedures, with significant decreases in the number of blepharoplasty and rhinoplasty procedures. Conclusions:. Understanding the changing practice patterns of ABPS diplomates is essential to define the direction that our specialty is taking over time, and to guide program directors in plastic surgery on areas of focus for appropriate training of plastic surgeons.

Background:. Current understanding of medical debt among various income ranges and insurance carriers is limited. We analyzed median household incomes, insurance carriers, and medical debt of plastic surgery patients at a major metropolitan children’s hospital. Methods:. A retrospective chart review for zip codes, insurance carriers, and account balances was conducted for 2018–2021. All patients were seen by members of the Division of Pediatric Plastic Surgery at Ann and Robert H. Lurie Children’s Hospital of Chicago. Blue Cross was reported separately among other commercial insurance carriers by the hospital’s business analytics department. Median household income by zip code was obtained. IBM SPSS Statistics was used to perform chi-squared tests to study the distribution of unpaid account balances by income ranges and insurance carriers. Results:. Of the 6877 patients, 630 had unpaid account balances. Significant differences in unpaid account balances existed among twelve insurance classes (P < 0.001). There were significant differences among unpaid account balances when further examined by median household income ranges for Blue Cross (P < 0.001) and other commercial insurance carriers (P < 0.001). Conclusions:. Although patients with insurance policies requiring higher out-of-pocket costs (ie, Blue Cross and other commercial insurance carriers) are generally characterized by higher household incomes, these patients were found to have higher unpaid account balances than patients with public insurance policies. This suggests that income alone is not predictive of unpaid medical debt and provides greater appreciation of lower income families who may make a more consistent effort in repaying their medical debt.

Background:. Medical students interested in plastic surgery may become discouraged by barriers to career development during residency training. This study surveyed plastic surgery program directors (PDs) and chiefs/chairs to highlight the pathway followed by academic leaders in these positions. Methods:. A self-administered anonymous survey was sent to a list of 189 PDs and chiefs/chairs identified via plastic surgery residency programs’ websites. Chi-squared tests assessed answer distributions. Results:. Of the 189 recipients (25.9%), 49 completed the survey. Respondents’ medical school graduation range was 1973–2009. Seventeen respondents entered a plastic surgery residency directly after medical school, and 32 began in another specialty. Comparison between these two groups showed no significant differences in preference rank of their program (P = 0.671). A total of 18 respondents conducted an academic enrichment year, but timing of this year differed significantly based on the initial specialty match (P = 0.012). There was no significant perceived difficulty in gaining recognition by gender (P = 0.107) or race (P = 0.125). Six respondents did not match into the specialty of first choice; five did not complete their initial residency programs; three did not match into plastic surgery at first attempt. Conclusions:. Information on residency training pathways and barriers to career development of current academic leaders will improve transparency as to potential stumbling blocks that current PDs and chief/chairs of plastic surgery residency programs have faced during their initial training. This will help current trainees anticipate these stumbling blocks and place these in perspective based on the experience of senior plastic surgeons.

Summary:. Surgical treatment of velopharyngeal insufficiency (VPI) after primary palatoplasty poses a difficult challenge in cleft care management. Traditional treatment options have shown improved speech outcomes but oftentimes lead to airway obstruction by constriction of the posterior pharynx. The buccinator myomucosal flap is an alternative flap used for VPI correction that re-establishes palatal length and velar sling anatomy by recruiting tissue from the buccal mucosa and buccinator muscle. We present innovative modifications to the original buccinator myomucosal flap by performing the procedure in one stage without a mucosal bridge, incorporating full-thickness buccinator muscle during flap elevation, and placement of bilateral buccal fat flaps. These refinements facilitate wound healing by providing a tension-free closure with both a well-vascularized myomucosal flap and interposed buccal fat flap to prevent scar contracture. Furthermore, no additional surgery is necessary for pedicle division.

Introduction:. Institutional partnerships between plastic surgery residency programs in the United States and providers in low- and middle-income countries can serve as bilateral and longitudinal capacity-building relationships. In the United States, obtaining approval for international rotations by a home institution and national review committee is highly encouraged but not required before resident international engagement. Acquiring approval at the institutional level is the first step to allow trainees to participate in international rotations on elective time rather than on vacation time. National approval through the American Council of Graduate Medical Education and American Board of Plastic Surgery allows cases to count toward the resident’s yearly case log. Methods:. All 101 integrated and independent plastic surgery program directors/coordinators were asked to participate. The survey identified the requirements and details of existing international rotations. Results:. In total, 57 programs responded (56% response rate) to the survey. An estimated 54% of all programs offered international rotations to their residents, and 94% of these programs obtained institutional approval. Additionally, 69% of these programs have received national approval. Conclusions:. Institutional requirements for programs to provide international rotations vary significantly across institutions, which results in disparate experiences for residents and poses potential risks to international partners. This study will help promote transparency regarding international rotation requirements and better equip faculty to enhance international rotations that cater to the needs of the institution, residents, and most importantly, the host countries.

Background:. Patients with cleft lip often undergo a primary rhinoplasty at the time of lip repair, and further surgical correction with secondary cleft rhinoplasty (SCR) is often warranted for improved form and function. The purpose of this study was to better elucidate current practice patterns and trends for how SCR is performed in the United States. Methods:. We administered a survey to team surgeons affiliated with cleft lip and palate care teams approved by the American Cleft Palate Craniofacial Association (ACPA). Results:. We received responses from 40 ACPA-approved teams for a response rate of 20.7%, with 59 total ACPA team surgeons completing the survey. 88.1% of surgeons perform intermediate cleft rhinoplasties. Among those who perform an intermediate cleft rhinoplasty, the mean age at which they would first consider the procedure is 5.83±2.66 years. The mean age for consideration of definitive cleft rhinoplasty was 15.86 ± 1.73 years. In both unilateral and bilateral cleft lips, a closed approach was more common in intermediate rhinoplasty, while an open approach was more common in definitive rhinoplasty (P < 0.001). The use of autologous grafts was more common in definitive rhinoplasty (P < 0.001), with 65% of respondents utilizing autologous grafts in greater than three-quarters of their procedures. Conclusions:. When comparing intermediate with definitive cleft rhinoplasty, we found significant increase in the use of open techniques, autologous cartilage use for augmentation of the nasal tip, dorsal nasal support, and columellar sup- port. The considerable variability among surgeons highlights the lack of consensus regarding SCR.

Background:. The American Board of Plastic Surgery has been collecting practice data on operative repair of flexor tendon lacerations since 2006, as part of its Continuous Certification program. Methods:. Data on operative repair of flexor tendon lacerations from 2006 to 2014 were reviewed and compared with those from 2015 to 2020. National practice trends observed in these data were evaluated and reviewed alongside published literature and evidence-based medicine. Results:. In total, 780 patients with flexor tendon laceration injuries were included. Mean patient age was 38 years; mean time between tendon injury and first evaluation was 4 days, and the mean time from injury to operative repair was 12 days. Four-strand sutures remain the most common technique of tendon repair (57%). In the recent cohort, there were significant decreases in tourniquet use (94% versus 89%), general anesthesia (88% versus 74%), and monofilament sutures (44% versus 35%), with a significant increase reported in preserving the A1 pulley (20% versus 29%). Postoperative movement was described as “almost full range of motion” or “good” in 70% of cases, and 74% of patients were satisfied with their results. Postoperative adverse events were reported in 26% of cases, with the most common complications being tendon adhesions (14%) and rupture (3%). Conclusions:. Review of The American Board of Plastic Surgery tracer data for operative repair of flexor tendon lacerations establishes a framework by which surgeons can evaluate how their current practice aligns with that of their peers, and whether their practice patterns remain current relative to recommendations from evidence-based medicine.

Background:. Applicant preferences for required research and global surgery experiences during plastic surgery training have not been previously studied. Methods:. An anonymous survey was sent to integrated plastic surgery applicants from consecutive residency application cycles (2018–2020). Research and global health experiences before residency were elicited, along with the interest to continue these activities. Data were analyzed using frequency distributions and chi-square test of independence. Results:. Seventy-eight former plastic surgery applicants responded to the survey (15.7% response rate). Most participants (65%) viewed time for research as important when evaluating residency programs. Fewer respondents (10%) ranked programs with a required research year higher, whereas 47% ranked those programs lower and 43% did not factor it into their decision-making. Less than one-third of respondents (28%) reported prior global health experience, yet 44% viewed international opportunities as an important factor when ranking programs, and the majority (72%) stated plans to participate in global surgery during residency. Past experience on a global health trip predicted a strong preference for longer rotations (P = 0.003) and willingness to use vacation time to participate during residency (P < 0.001). Conclusions:. Research was an important consideration in residency selection, but a few preferred a residency program with a dedicated research year. Although applicants had limited experience with global surgery, the majority intended to get involved during residency. Understanding factors that influence applicants’ interests in residency programs may better equip programs with information to create enriching experiences and attract the most qualified applicants.

Background:. Plastic and reconstructive surgery (PRS) residency training can be completed through multiple pathways. Current residents’ experiences regarding these different routes have not been previously described. The objective of the present study was to describe the educational pathways taken by current PRS residents in the United States. We hypothesized that there would be a small cohort of current PRS residents who were initially unsuccessful in matching into an integrated residency. Methods:. An online survey was sent to PRS residents across all training years from October 2020 to January 2021. The survey collected information about residents’ match history, experience after not matching, and narrative comments on their route to residency. Public match data from the past 20 years (2001–2021) were also summarized with descriptive statistics. Results:. One hundred seventy-four residents responded (response rate 15%; 174/1158). Of these, 133 applied to integrated programs as senior medical students, and 15 (11%) did not match after applying as a senior medical student. Unmatched applicants took multiple different routes to PRS, including participating in the Supplemental Offer and Acceptance Program, reapplying, transferring after some general surgery training, and completing an independent PRS residency. Three-fourths (76%) of independent program residents did not originally apply to the integrated match. Conclusions:. An initial unsuccessful match result does not portend that one will not be able to train for a career in PRS. Our findings illustrate the potential routes to successful completion of PRS residency training, both for unmatched applicants and residents who develop later interest in PRS.

Background:. The American Board of Plastic Surgery has been collecting practice data on metacarpal fracture operative repair since 2006 as part of its Continuous Certification process. These data allow plastic surgeons to compare their surgical experience to national trends. Additionally, these data present the opportunity to analyze those trends in relation to evidence-based medicine. Methods:. Data on metacarpal fracture operative repair from May 2006 to December 2014 were reviewed and compared with those from January 2015 to March 2020. National practice trends observed in these data were evaluated and reviewed alongside published literature and evidence-based medicine. Results:. In total, 1160 metacarpal fracture repair cases were included. Outpatient (as opposed to inpatient) operative repairs have been trending upward, from 50% to 61% (P < 0.001). Most repairs were performed under general anesthesia (68%), and there was a decrease in the use of regional anesthesia between our two cohorts (14%–9%; P = 0.01). An open reduction with internal fixation was the most popular technique (51%), and a decrease in the use of closed reduction with splinting was observed (16%–10%; P = 0.001). Stiffness was the most commonly reported adverse event. Topics addressed in evidence-based medicine articles but not tracer data included interosseous wiring, which has shown success in spiral shaft fracture treatment with minimal complications, and nonoperative management. Conclusion:. As evidence-based recommendations continue to change with additional research inquiry, tracer data can provide an excellent overview of the current practice of metacarpal fracture repair and how effectively physicians adapt to remain aligned with best practices.

Background:. Evidence regarding whether medical school research portends resident research is limited. This information will provide program directors with data that may be useful for selecting applicants with a commitment to continued academic productivity. Methods:. A questionnaire distributed via the American Society of Plastic Surgeons Resident Council to residents in 44 plastic surgery training programs in May 2020 assessed participation in dedicated research years during medical school, the number of publications completed before residency, and the total number of publications by each resident at the time of the survey. One-way ANOVA and post hoc analysis determined significant associations between publication count and number of research years. Results:. Of the 256 included respondents, 203 did not complete a research year during medical school, 44 completed 1 research year, and nine completed 2 research years. Mean publications before residency were higher for participants who took 1 or 2 research years (9.88 and 27.60, respectively) compared with those who did not (4.83, P < 0.001). A comparison of total publications during residency similarly revealed increased productivity by individuals who took 1 or more research years; however, there was no difference between the number of publications completed during residency for individuals who took 1 versus 2 years (P = 0.23). Conclusions:. Residents with research experience during medical school continue to produce an increased number of publications during residency compared with those without, suggesting dedicated research years taken during medical school serve as a predictor of academic productivity in plastic surgery residents.

Tissue expansion is an integral procedure of the vast majority of breast reconstruction and has a significant impact on the final clinical outcomes. Therefore, technological advances leading to a fewer number of unfavorable outcomes and a decrease in complication rates are imperative. In this study, using a porcine model, we investigated an effect of acellular dermal matrix (ADM) used as a tissue expander cover on the dermal changes induced by mechanical forces during tissue expansion. After 14 days of expansion, skin samples were collected from one animal, while the second animal underwent radiation, and tissue was collected 8 weeks later. Tissue expanded without the use of ADM and unexpanded skin served as the controls. Collected skin biopsies were used for histological and immunohistochemical evaluation, and for gene expression analysis. We revealed that the biological cover incorporation into host tissue is facilitated by macrophages without inducing a broad inflammatory response. The utilization of ADM mitigated disruption in the dermal structure, excessive collagen deposition, and capsule formation in non-irradiated expanded skin. The protective effect was not fully maintained in irradiated skin. These results demonstrate that tissue expansion might be improved by using the tissue expander cover.

Summary:. The COVID-19 pandemic limited the ability of medical students to participate in plastic surgery sub-internships and to attend residency interviews in person during the 2020–2021 match cycle. A podcast and accompanying online directory were created to introduce integrated plastic surgery residency programs to medical students from the perspective of current residents. Since July 2020, a total of 49 plastic surgery residents representing 42 programs have participated in the podcast. Topics of discussion included program logistics, faculty leadership, and aspects of resident lifestyle of interest to medical students and future residency candidates. The podcast has had a total of 5072 downloads (mean 121 downloads per episode). The majority of listeners (90%) were in the United States. Twenty-five plastic surgery applicants who participated in the 2020–2021 National Resident Matching Program match cycle responded to a feedback survey. Listeners reported that the podcast was useful for preparing for interviews, making rank lists, and learning about programs that they otherwise would not have considered. Most listeners (90%) ranked the podcast as one of their top three resources for learning about plastic surgery programs during the application and interview process. Future directions include completion of episodes for all integrated plastic surgery programs and expansion to other surgical subspecialties and plastic surgery fellowships.

Purpose: Since 2008, The American Board of Plastic Surgery (ABPS) has collected clinical practice data on Dupuytren’s contracture repair as part of their Continuous Certification (CC) process. Submitted twice every ten years by each plastic surgeon, this collection can help describe clinical trends in Dupuyren’s contracture repair as they relate to Evidence-Based Medicine (EBM) articles published in this timeframe. Methods: Cumulative tracer data for Dupuytren’s contracture repair from February, 2008 through December, 2014 were reviewed and compared to data from January, 2015 through March, 2020 with the goal of identifying national practice trends. These trends were then evaluated alongside EBM reviews published in 2010, 2014 and 2017. Results: As of March 2020, 230 cases of Dupuytren’s contracture were included in the tracer. The median age at time of surgery was 65 years (range, 38-91 years), and the average age of disease onset was 47 years. The most common surgical technique was limited fasciectomy, comprising 62% of cases. There were no postoperative adverse events reported in 77% of cases. The most common complications were loss of finger flexion (3%) and skin loss (2%). Topics addressed in EBM articles but not tracer data included adjuvant treatments and non-operative techniques such as tamoxifen administration. The use of minimally invasive procedures such as percutaneous cordotomy (0% vs. 13%) and collagenase injections (0% vs. 9%, p = .001) showed significant increases between the two time periods. More invasive procedures such as radical fasciectomy decreased in popularity (34% vs. 16%, p = .002). Use of Z-plasty also decreased between 2015 and 2020 (67% vs. 45%, p < .001). General anesthesia was the most commonly used form of anesthesia, being employed in 54% of tracer cases. There was an increase in the use of Bier block regional anesthesia (1% vs. 9%, p = 0.029) as well as in the use of epinephrine for hemostasis (0 vs. 8%, p = 0.006). Significant changes were also noted in post-operative management, including a decrease in the employment of formal postoperative hand therapy. This is consistent with evidence showing that it has no significant clinical benefit. Conclusion: The tracer data collected on Dupuytren’s contracture repair over a twelve-year period allow us to describe national trends in presentation and surgical techniques, and can help plastic surgeons evaluate their surgical practice in the context of these trends and EBM.

Purpose: Tissue expansion (TE) is based on the skin’s exceptional ability to regenerate under mechanical stress and is widely used to repair skin defects. However, knowledge about molecular mechanisms involved in maintaining skin integrity and homeostasis is limited. The present study aims 1) to elucidate the role of myofibroblasts in the mechanism of adaptation to mechanical stress exerted by an inflated tissue expander, and 2) to describe morphological changes in collagen structure that could lead to the re-establishment of dermal tension. Methods: TE was performed on a porcine model. Each expander was placed subcutaneously over the ribs and two weeks later inflated with 30 cc of saline to induce subtle tension. After 1 day (acute stretch) and 7 days (sub-acute stretch) of expansion, the full-thickness skin biopsies were collected from the apex of the expander and control unexpanded skin (contralateral sites). Skin samples were fixed in formalin and embedded in paraffin for histological evaluation (Russell-Movat Pentachrome staining) or fixed in 4% PFA and embedded in OCT for immunohistochemistry staining (IF) of α-smooth muscle actin (α-SMA), a marker of myofibroblast. Area of fluorescent signal from α-SMA was calculated using ImageJ while collagen morphology was evaluated optically after staining. Results: We compared the presence of α-SMA fluorescence between control biopsies and expanded biopsies after 1-day and 7-days of stretch. The immunofluorescence staining revealed 2.32 times more α-SMA fluorescent staining in skin expanded for 1 day (p = 0.0065) and 2.19 times more α-SMA fluorescence in skin expanded for 7 days (p = 0.0047). The increase in number of α-SMA positive cells were mostly observed in the outermost 400µm of papillary dermis. Histological staining showed minimal collagen morphological changes in both the papillary and reticular dermis after 1-day of expansion. However, shortening of fibril length, increased density, and increased disorder were observed in the papillary dermis collagen after 7-days of subtle expansion.

Purpose: Acellular dermal matrix (ADM) is used to create an inferolateral sling nearly three-quarters of the time in breast reconstruction and has proven a valuable alternative to total submuscular coverage of the implant. Previous work has demonstrated decreased inflammation and fibrosis of the pocket lining the ADM sling; however there has been minimal investigation into the role of ADM in skin growth and regeneration. The present study evaluates morphologic and molecular changes mediated by use of ADM in tissue expansion. Methods: Two tissue expanders, one wrapped in ADM, were placed subcutaneously on the back of Yucatan minipigs. All expanders were inflated with two weekly fills of 60cc of normal saline and skin biopsies were harvested after two weeks of expansion from each condition: control, tissue expansion (TE), and tissue expansion with ADM (TE+ADM). Three biopsies per condition were embedded in paraffin or OCT medium and stained with Russell Movat Pentachrome and Immunofluorescence of CD31, respectively. Collagen in the papillary dermis of pentachrome-stained images were analyzed using an ImageJ plug-in, Fibril Tool, that applies circular statistics to estimate average fibril orientation as the direction angle from -90 to 90 with respect to the x-axis. One-way ANOVA evaluated seventy-two measurements per condition and post-hoc analysis with Tukey’s HSD test identified significant comparisons between the groups. Number of fluorescent cells expressing CD31 (a marker of endothelial cells) were counted on 12 photographs per condition. P-values ≤ .05 were considered significant. Total deformation was calculated using a computational model and isogeometric analysis. Results: The mean fibril orientation of TE and TE+ADM underwent -85% change (P < .001) and -15% change (P = .65), respectively, compared to control. Three times more CD31+ cells were observed in TE+ADM compared to control (P < .001), but no significant changes were detected in TE alone. Histogram of total deformation revealed more even distribution of forces in TE+ADM compared to TE and control. Conclusions: The use of ADM in a porcine tissue expansion model appears to mitigate disarray of the collagen network in adjacent tissue, thereby creating a more extensive, yet even, distribution of stretched skin. This observation, combined with the finding of increased angiogenesis, suggests it is the incorporation of ADM that confers these protective benefits. Future studies will evaluate whether the protective effects of ADM can serve to improve TE in compromised tissue beds, as seen in patients undergoing TE concurrent with perioperative radiation therapy.

Purpose: Tissue expansion (TE) is commonly utilized to promote skin growth prior to reconstructing a defect or deformity. In spite of its ubiquitous use, the role of molecular modulators during TE, such as microRNAs (miRNAs), has not previously been studied. MiRNAs are small endogenous molecules that regulate many biological processes, including cell proliferation, differentiation, and inflammatory response. Here, we investigate genome-wide changes in miRNA expression in skin during TE. Methods: Changes in miRNA expression were evaluated in a porcine TE model. Full-thickness skin biopsies were collected after 1 hour, 24 hours, 3 days, and 7 days of expansion, as well as from unexpanded skin (control). RNA extracted from biopsies was analyzed with next-generation sequencing (NGS). Differential expression analysis was performed using R software with the Bioconductor-DESeq2 package. Results were corrected for multiple testing using the Benjamini-Hochberg method. A combination of adjusted p-value < 0.05 and | log2 (fold change) | > 1 were used as the threshold to determine the significance of differentially expressed (DE) miRNAs. Potential target genes for DE miRNAs were identified by in silico analysis using three data bases: miRDB, miRTarBase, and DIANA Tools with Tarbase. Functional enrichment analysis of target genes was performed using the g:GOSt functional profiling tool, and results were visualized using R and Cytoscape software. Results: We identified 52 miRNAs that were differentially upregulated (n = 18) or downregulated (n = 34) during at least one of the tested timepoints during TE. At the four time points (1 hour, 24 hours, 3 days and 7 days), there were 15, 6, 22, and 20 DE miRNAs, respectively. Eight miRNAs (ssc-miR-193a-5p, ssc-miR-21, ssc-miR-9-1, ssc-miR-708-3p, ssc-miR-212, ssc-miR-196a, ssc-miR-15b, ssc-miR-184) were DE at more than one timepoint. The comparative analysis showed 9, 4, 16 and 15 unique miRNAs after 1 hour, 24, hours, 3 days and 7 days of TE, respectively. Gene Ontology and KEGG pathway analyses for predicted target genes demonstrated enrichment in cellular processes related to metabolism, transcription, translation, signal transduction, cell differentiation, migration, and angiogenesis.