About

David Michael Stepien is an Assistant Professor of Surgery at Duke University, specializing in Plastic, Maxillofacial, and Oral Surgery. He is part of the Integrated Plastic and Reconstructive Surgery Residency Program. His role involves providing expert surgical care and advancing research in his field, contributing to the educational mission of Duke Surgery.

Research topics

• Biology
• Cell biology
• Internal medicine
• Medicine
• Cancer research
• Chemistry
• Immunology
• Pathology
• Anatomy
• Genetics

Selected publications

• Plastic surgery on Instagram: where do we stand on racial diversity and inclusion?

  Journal of Social Media Research · 2025-03-02

  articleOpen access

  Plastic surgeons use Instagram to expand their practices to accommodate growing interest in plastic surgery. Thus, it is important to assess whether the depiction of plastic surgery on Instagram is inclusive. This study aimed to analyze the racial representation of posts by United States (US) board-certified plastic surgeons and its impact on engagement with the content. Instagram accounts of US board-certified plastic surgeons active from February 1, 2023 – April 12, 2023, were randomly chosen. For procedural posts, the engagement and race of both the patient depicted and the surgeon were collected. ANCOVA was performed to explore whether patient race influenced engagement. Additionally, patient-surgeon racial concordance was investigated. 2,157 posts from 120 accounts were analyzed. White patients were overrepresented compared to the reported demographics of plastic surgery patients. Asian and Hispanic patients were underrepresented. Posts featuring Black patients in our sample had significantly more views, likes, and comments than White patients in the Southeast when controlling for other covariates. However, race was not a significant predictor of engagement per follower. Hispanic plastic surgeons were underrepresented compared to the demographics of practicing plastic surgeons. 88 of 120 accounts had > 50% patient-surgeon racial concordance. 23 had 100% concordance, all featuring White patients/surgeons. The depiction of plastic surgery on Instagram of patients and surgeons can become more racially inclusive. This will likely bring more engagement to this content, resulting in the growth of plastic surgery as a field and increased perceived accessibility to plastic surgery.

  PublisherOA PDFDOI

• High Definition Magnetic Resonance Imaging of Nasal Tip Ligaments Illustrates Rationale for Ligamentous Preservation

  Plastic & Reconstructive Surgery · 2025-11-17

  article

  BACKGROUND: Although preservation rhinoplasty was described many years ago, it has recently been brought to the forefront of our field. Skin and soft tissue envelope (SSTE) preservation is of particular interest as it prevents the previously-accepted disassembly and reconstruction of the nasal tip. This ligamentous anatomy has only been described through gross dissection, which is limited. MRI of the nasal tip would give a more holistic understanding of this ligamentous anatomy. OBJECTIVES: To provide a more complete anatomic description of the nasal tip ligaments through high-definition MRI. Additionally, to apply this knowledge through our technique of tip ligament preservation and suspension. METHODS: Nasal specimens were harvested from cadavers and processed through a fixation and contrast protocol. Imaging of specimens was completed in a high-definition (55 µm) small-animal MRI scanner. Image analysis with focus on identification of insertion, origin, and course of nasal tip ligaments was completed by all authors independently. The group's tip ligament preservation technique was described. RESULTS: The cartilaginous (septum and lower lateral cartilages) and ligamentous (interdomal, intercrural, and Pitanguy's) structures of the nasal tip were identified. The insertion, origin, and course of the above ligaments was analyzed and further-described. Segmentation of nasal tip structures was completed to create a three-dimensional model for further study. CONCLUSION: This is the first study to utilize high-definition MRI to define the nasal tip support ligaments. A three-dimensional model was created to better understand structural relationships. Through anatomic analysis and technique description, surgeons will now be better-equipped to abide by SSTE preservation techniques of the nasal tip.

  PublisherDOI

• What are Board-Certified Plastic Surgeons Posting on Instagram?

  Aesthetic Plastic Surgery · 2024-06-21 · 4 citations

  article
  PublisherDOI

• Art and Safety of Gluteal Augmentation

  Clinics in Plastic Surgery · 2023-08-02 · 1 citations

  review1st author
  PublisherDOI

• Umbilicoplasty in Abdominoplasty: Modifications for Improved Aesthetic Results

  Aesthetic Surgery Journal Open Forum · 2021-06-19 · 13 citations

  articleOpen access

  Umbilicoplasty is a key component of any abdominoplasty as the umbilicus has been described as the central aesthetic subunit to the abdomen. Here, we describe our preferred technique for umbilicoplasty which involves a half-moon design with periumbilical defatting which in our hands produces consistent, aesthetically pleasing results.

  PublisherOA PDFDOI

• 4: Peripheral Nerves Engage in Reciprocal Neuro- and Angiogenic Crosstalk With SMCs in Extremity Trauma

  Plastic & Reconstructive Surgery Global Open · 2021-07-01 · 1 citations

  articleOpen access

  Purpose: Existing literature describes the interdependence between neurotrophic and vascular signals in the central nervous system. We hypothesize a similar crosstalk important to extremity healing involving the peripheral nervous system and angiogenic cells. Nerves are difficult to capture via axons found in the periphery alone. Thus, we have interrogated from publicly available single-nuclei transcriptomic data of peripheral nerve soma (dorsal root ganglia), injured by physical transection or chemically induced pain. We present a combined analysis of extremity polytrauma (burn/tenotomy HO model) and peripheral nerve (post-injury/pain DRG model) to determine if there is expression of vascular signals by nerves and reciprocal neurotrophic signals by cells local to the injury site. Methods: A 30% dorsal burn and Achilles transection was performed in C57/BL6J mice. The tendon site tissues were harvested from baseline (t0) and day 7, 42 after induction. Samples were prepared for library generation on a 10x Genomics Chromium Controller, sequenced on a Illumina HiSeq 4000, and analyzed with Cell Ranger Software for pre-processing and alignment to the mm10 genome. DRG analyses and clusters were abstracted from NIH-GEO (GSE154659). Downstream analyses including unsupervised clustering downstream analyses were performed with Seurat. Results: We first examined candidate neurotrophins and vascular signals in nerve (DRG), finding robust upregulation of Bdnf and Vegfa . In HO, the site of injury contains many cells that may potentially respond to these signals. Indeed, in sequencing data from the pre-HO anlagen, endothelium and smooth muscle cell populations express upregulation for receptors to the nerve-derived Vegfa via Flt1 /VEGFR1. This population in addition to being sensitive to the VEGFA ligand, also demonstrates upregulation of Ngf, signifying a potential vasculo-neuro axis where a vascular signal induces endothelium/SMCs to produce neurotrophic signals. Completing the circuit, the original DRG cells and by logical extension, regenerating peripheral nerves, are highly enriched for the neurotrophin receptors: Ntrk1/ TrkA (responsive to the SMC derived NGF), Ntrk2/ TrkB (responsive to the nerve-autonomous BDNF), and Ntrk3/ TrkC (partial combined NGF/BDNF response). This potentially signifies a feedforward loop where peripheral nerve induces angiogenesis which in return, promotes nascent nerve ingrowth in a cyclical process. Indeed, in targeted knockout of a local VEGFA source ( Vegfa Prrx1 mice), the injury site demonstrates parallel reduction in vascular density (77%) and reduction in nerve fiber frequency (62%) within the HO site. Conclusions: These findings represent the first work characterizing the coordination between neurogenic and angiogenic transcription programs following extremity trauma. We demonstrate through NextGen sequencing, evidence of neuroangiogenic crosstalk following musculoskeletal/neural injury. This VEGFA/NGF axis involves vascular signaling as a potential source for additional proliferation of NGF expressing pericyte/SMCs. The presented data describe the potential nerve-driven regulation contributing to the formation of HO at the extremity that with antagonism or inhibition may lead to better treatments for aberrant extremity wound healing.

  PublisherDOI

• NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma

  Nature Communications · 2021 · 86 citations

  • Cell biology
  • Biology
  • Medicine

  Pain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation.

  PublisherOA PDFDOI

• The TrkA Antagonist AR786 Prevents Heterotopic Ossification

  The FASEB Journal · 2021-05-01

  article

  Soft tissue trauma can result in the pathologic formation of cartilage and bone outside of the skeleton, termed heterotopic ossification (HO). Therapeutic options for treatment of HO are lacking. We recently recognized the role of sensory nerve fibers in trauma‐induced HO through nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) signaling whereby the deletion of NGF‐TrkA signaling impairs axonal invasion and blunts osteochondral differentiation after HO induction in a mouse model. Given this observation, we hypothesized that utilization of a small molecule antagonist for TrkA in clinical development, AR786, would demonstrate therapeutic benefit in the prevention of HO. Association of NGF and innervation with human HO of the posterior longitudinal ligament (HOPLL) was analyzed by microarray and immunohistochemistry . In a mouse model, trauma‐induced HO was generated by the combination of cutaneous burn and Achilles tenotomy in 10 week old C57BL/6J mice, which causes HO over a well characterized 9 week time period. NGF expression was examined by single cell sequencing, immunohistochemistry, and western blot. Dorsal root ganglion (DRG) from the innervating lumbar tracts were examined for pTrkA expression by immunohistochemistry. The phenotypic consequences of TrkA inhibition by AR786 on HO formation was next assessed (Vehicle, n=5 and AR786, n=5). Nerve innervation within the injury site was visualized using immunohistochemistry stained with Beta III Tubulin (TUBB3) and confocal microscopy. Abnormal chondrogenesis was assessed by cartilage histomorphometry, and immunohistochemical detection (SOX9 and COL2). Data were presented as Means ± SD. Results showed that NGF and associated downstream NGF signaling were increased among HOPLL patient cells. NGF immunoreactivity was present in perivascular cells adjacent to HO, fibroblastic cells, and bone‐associated cells. Increased nerve fibers were present surrounding HO and axonal sprouting was confirmed by neural antigen S100 and neurofilament SM31 in human HO tissue sections. During HO progression in mice, NGF, proNGF, and pTrkA were upregulated following HO induction. Nerve frequency was significantly reduced with AR786 treated animals compared to vehicle control in uninjured ( p <0.001, Vehicle; 548.2 ± 118.0 vs. AR786; 104.2 ± 47.9, µm 3 ) and 3‐weeks post‐injury ( p <0.001, Vehicle; 3255.6 ± 1405.1 vs. AR786; 462.8 ± 201.1, µm 3 ). Consequently, reduced axonal ingrowth significantly delays in ectopic cartilage formation ( p <0.01, Vehicle; 0.33 ± 0.07 vs. AR786; 0.07 ± 0.06, mm 2 ). In conclusion, NGF‐TrkA signaling mediates crucial functions in human and rodent HO, and inhibition of TrkA‐expressing neural inputs by AR786 abrogates HO progression. These findings suggest that NGF‐TrkA signaling inhibition can be a potential therapeutic use in HO patients as negative regulator of HO disease progression.

  PublisherDOI

• A-120 Practice Effects on Repeat Neuropsychological Assessment of Adults with Chronic Severe TBI

  Archives of Clinical Neuropsychology · 2020-08-28

  articleOpen access1st authorCorresponding

  Abstract Objective This study examined whether practice effects caused by repeated exposure to test materials during serial assessment significantly impacts the performance of adults with chronic severe traumatic brain injury (sTBI), given the severe memory impairment typical of this population. This study sought to describe the pattern of practice effects on repeat neuropsychological testing for this population. It was hypothesized that practice effects would be diminished for individuals with chronic sTBI. Method This study utilized longitudinal archival data collected as part of an annual neuropsychological assessment battery administered to 43 individuals receiving post-acute rehabilitation services at a structured multisite day treatment program. Each participant was tested at two time points which differed by an average of 13 months. The battery consisted of the Texas Functional Living Scale (TFLS), Trail Making Test (TMT), Brief Mood Survey, Neuropsychological Assessment Battery (NAB) Screening Module (NAB-SN), and Judgment subtest from the NAB Executive Functions Module (NAB Judgment). Results Practice effects were determined based on reliable improvement (p < .05) in scores across test administrations. A Reliable Change Index (RCI) was calculated for each test based on the method proposed by Jacobson and Truax (1991). Results revealed reliable improvements in performance for the NAB-SN Attention domain (RCI = 3.69), NAB Judgment subtest (RCI = 10.14), and TFLS Total Score (RCI = 4.38). Conclusion This study indicates that adults with chronic sTBI demonstrate significant practice effects primarily on measures associated with functional living skills. These findings suggest that repeat testing in this population may be less susceptible to the influence of practice effects.

  PublisherOA PDFDOI

• Abstract 89: Identifying The Myeloid Subpopulation Responsible For Tissue Fibrosis Across Organ Systems Via Machine Learning Parameterization And Predictive Transcriptomics

  Plastic & Reconstructive Surgery Global Open · 2020-04-01

  articleOpen access1st authorCorresponding

  Purpose: Fibrosis secondary to ischemia and musculoskeletal polytrauma is a clinical problem common in plastic surgery with limited effective therapeutics currently available. Until recently, high throughput analyses of fibrosis have been untenable. We developed an automated parameterization of fibrosis histology via machine learning (ML) methods capable of distinguishing healthy from fibrotic muscle, correlated with transcriptomic profiles of infiltrating macrophages following musculoskeletal polytrauma. Furthermore, we established a transcriptomic analysis pipeline of multiple muscle and organ fibrosis models using single cell RNA sequencing (scRNAseq) to allow identification of a “fibrotic” macrophage. We hypothesize that inflammatory and fibrotic myeloid cell phenotypes are similar across musculoskeletal and visceral organ systems and that proteomic and transcriptional profiles can be used to predict homeostasis, injury and fibrogenesis. Methods: Ischemia/reperfusion of the mouse hindlimb with concomitant cardiotoxin injection into the tibialis anterior (IR/CTX) was induced in mice with genetic (LysmCre;Tgfb1fl/fl) and pharmacologic (TGFB1-Fc ligand trap) Tgfb1 deletion. H&E, Masson Trichrome, and picrosirius red histology was performed at 1 week post injury (n=3-4/group). Automated quantification of picrosirius micrographs were performed with a novel image processing pipeline resulting in a panel of 13 relevant fiber and branchpoint parameters and t-SNE dimensional reduction. Separately, we performed 10X scRNAseq on IR/CTX injured tibialis anterior muscle at homeostasis and 3 days post-injury. For comparison studies, IR/CTX macrophages were isolated and aggregated with additional macrophages from distinct murine data sets for examination of gene expression profiles: wild-type muscle 1-2 days following gluteus muscle crush (data gifted by Regeneron), lung tissue macrophages 14 days after asbestos (GSE127803), and 0, 3, 6 days after LPS (GSE120000) exposure. Results: IR/CTX injury with inhibition of TGF-β1 signaling recapitulated the appearance of uninjured muscle with ML delineating distinct, self-aggregating clusters between WT injury vs. all other groups. While injured and naive muscles were robustly separated, conditional Tgf-β1 deletion and systemic sequestration were observed as intermediate populations. Unsupervised clustering in IR/CTX TA muscles resulted in 11 (uninjured) and 8 (IR CTX) clusters. Examining for overexpression of gene families in TGFβ1 signaling, we observed stark contrast between uninjured and IR/CTX macrophages suggesting an important role in fibrosis. In order to determine phenotypic resemblance of macrophages between muscular polytrauma vs. crush vs. inhalation injury, we visualized the combination of IR/CTX, muscle crush, and lung macrophages, demonstrating overlap. Furthermore, we observed high levels of Tgfb1 expression in Adgre+Csf3r- macrophages of muscle crush and lung injury, suggesting a shared myeloid phenotype associated with spatially distinct niches of fibrosis. Conclusions: ML methods can aid in high-throughput analysis of muscle fibrosis histology. Given transcriptomic similarities between macrophages from IR, muscle crush, and inhalation induced fibrosis, it is possible that these cells may exhibit a conserved mechanism across organ systems and models, elucidating important parallels that could be amenable to ML and identification of important common therapeutic targets.

  PublisherDOI

Frequent coauthors

• Daniel G. Remick

  Boston University

  29 shared

• Alex B. Lentsch

  University of Cincinnati

  17 shared

• Michael D. Goodman

  University of Cincinnati

  17 shared

• Timothy A. Pritts

  University of Cincinnati

  17 shared

• Charles C. Caldwell

  University of Cincinnati Medical Center

  16 shared

• Dennis J. Hanseman

  University of Cincinnati

  16 shared

• Bryce Robinson

  Association Clinique et Thérapeutique Infantile du Val de Marne

  16 shared

• Sung Hyun Yang

  Korea Institute of Radiological and Medical Sciences

  16 shared