Unmatched. What's Next? Is a Preliminary Year of Residency or Research Fellowship Better for Reapplicants to Plastic Surgery?

Background: Plastic and reconstructive surgery is one of the most competitive residency programs, and given the increased number of applicants for a relatively fixed number of positions, successfully matching is a challenge. Match rates have declined since 2018, with a match rate of ~55% in 2022. Two common options before reapplying are a preliminary year of residency (preliminary year) or a research fellowship. This study investigated which option is more beneficial for reapplicants seeking a successful match. Methods: This retrospective study included all applicants to an integrated plastic and reconstructive surgery residency from 2015 to 2023. Two cohorts based on reapplication strategy (research fellowship or preliminary year) were created. Demographic, applicant, and match data were collected. Pearson chi-squared, Fisher exact, and Wilcoxon rank sum testing were performed. Results: In total, 125 reapplicants were included. Seventy-one (56.8%) reapplicants pursued a preliminary year, and 29 (23.2%) completed a research fellowship. Research fellowship reapplicants had a greater mean number of first author publications (8.8 versus 3.2, P < 0.001), non-first author publications (11.3 versus 5.9, P = 0.021), poster presentations (9.7 versus 6.0, P = 0.028), and oral presentations (11.8 versus 6.4, P < 0.001). Research fellowship reapplicants were more likely to match into plastic and reconstructive surgery (PRS) than preliminary year reapplicants, with 72.4% (n = 21) of research fellowship reapplicants matching into PRS compared with 39.4% (n = 28) of preliminary year reapplicants (P = 0.003). Conclusions: Research fellowship reapplicants demonstrated greater research productivity and were almost twice as likely to match into PRS compared with preliminary reapplicants.

Diversity Drives Representation: An Internal Audit of Gender Representation in Citation Practices of a Single Surgical Laboratory.

Background: Large-scale retrospective studies have identified implicit gender bias in citation behaviors across multiple medical fields. There are minimal resources to directly assess one's own citation behavior before publication at a laboratory level. In this study, we performed an internal audit of our own citation practices and behavior, looking at the representation of authors by gender in our own bibliographies. Methods: Bibliographies were collated from our laboratory's publications between 2015 and 2022 with a single senior author, who was excluded from participating in this study. Bibliographies were run through a simulation originally constructed and used by authors from the University of Pennsylvania that categorized authors of each article by gender: man or woman, according to external database records. Results: Of the 1697 citations, the first and last authorship sequences displayed to be 60.8% male/male, 10.1% male/female, 16.3% female/male and 12.8% female/female. Men-led articles within our laboratory cited 67.4% male/male articles in their bibliographies compared with women-led articles citing 53.9%. All laboratory bibliographies consisted of 77.1% male senior authors compared with 22.9% female senior authors. Conclusions: Our data confirm that a gender bias in citation practices exists at the laboratory level. Promisingly, these data also indicate that diversity within an individual laboratory group leads to diversity in representation; therefore, diversifying a team of researchers is prone to improve the overall work and success of the laboratory. We encourage laboratory groups to challenge their own biases by replicating their own results and discovering how these biases might be impacting their publications.

Can Electrical Stimulation Prevent Recurrence of Keloid Scars? A Scoping Review.

Objective: Keloids represent a symptomatic, aberrant healing process that is difficult to treat with high recurrence rates spanning from 55% to 100% if treated via excision without adjuvant therapy. Electrical stimulation (ES) has demonstrated findings that suggest it could reduce the recurrence rate of keloids after resection. Therefore, the aim of this study is to conduct a scoping review to investigate ES as an adjuvant therapy for decreasing keloid recurrence after excision. Approach: A scoping review was performed using PubMed and Web of Science databases. The search strategy encompassed terms linking keloids and various aspects of electrical stimulation. Results: Our search yielded 2,229 articles, of which 115 articles were analyzed as full text and 1 article met inclusion criteria. Despite this, ES has demonstrated other evidence that suggests its utility. ES has been shown to counter keloidic features by reducing mast cell counts, shifting wound composition from M2 to M1 macrophages, promoting angiogenesis, and controlling fibroblast orientation and location. An alternating current will orient fibroblasts perpendicular to the current without unintended migration. Innovation: Our study indicates that, based on a compilation of clinical and preclinical in vitro data, the optimal scenario for ES in the role of keloid treatment is after excision with a biphasic pulsed application and square waveform. Conclusions: ES could serve as a multifaceted, adjuvant treatment after keloid excision, steering the healing process away from keloid-associated characteristics. Its cost-effectiveness means it could be adopted globally, providing a strategy to mitigate the burden of keloids irrespective of other available treatments or economic conditions.

Livestreaming Microsurgery Education: An Avenue to Expand Global Plastic Surgery.

Microsurgery is a complex subspecialty requiring fine manual dexterity and a thorough understanding of microsurgical techniques, requiring years of training to reach proficiency. On a global scale, trainees may not have access to a longitudinal microsurgery curriculum and instead attend brief courses to learn microsurgical techniques, limiting their ability to practice the nuances of microsurgery. There remains a gap in global microsurgical education for trainees to have consistent educational exposure. This article presents a novel and easy to use software-based microsurgical system for virtual microsurgical teaching. In doing so, this system provides a free-of-cost and highly accessible avenue to deliver consistent microsurgical education worldwide.

Social media analysis of pain outcomes following targeted muscle reinnervation.

AIM: Targeted muscle reinnervation (TMR) was developed to improve myoelectric prosthesis control for amputees; however, it has become an area of interest in pain modulation. Evidences indicate that this procedure alleviates chronic pain in amputees. The primary objective of this study was to use social media analysis to understand patients' post-operative pain, satisfaction, and recovery time after TMR. METHODS: Data were collected from one Facebook group via posts and comments referencing TMR. Posts published between January 1, 2020, and March 24, 2023 were analyzed. Data collected included pain prior to surgery, pain in immediate post-op period, and change in pain after surgery. RESULTS: Forty-three individuals commented on their TMR experience. Among them, 31 had favorable surgical outcomes, 7 felt that the surgery worsened their pain or there was no significant change in their pain levels, and 5 commented during the initial post-operative period. Twenty-four patients described their pain in the immediate post-operative period and all patients said that the post-operative pain was worse than chronic pain. Among the 28 authors who commented on overall reduction in chronic pain, 24 reported that TMR reduced their pain, whereas 4 reported no change or worsened pain. CONCLUSIONS: The number of patients (24) who reported improvement in chronic pain aligns with the results in current literature suggesting that TMR is a viable treatment option for pain management. With the current medical management of similar conditions, up to 80% of patients remain unsatisfied with pain management. This analysis supports the evidence that TMR is an effective treatment for patients experiencing post-amputation pain.

Significantly Improved Cold Preservation of Rat Hind Limb Vascularized Composite Allografts Using the New PrC-210 Free Radical Scavenger.

Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation. Limbs were stored in 40 mL of the same perfusate at 4 °C for 48 h. Muscle punch biopsies were taken at set times over the 48 h cold-storage period and analyzed for caspase-3,7 activity, cytochrome C levels, and qualitative histology. A single 15 s perfusion of PrC-210-containing UW Solution conferred a dose-dependent reduction in CI-induced muscle cell death over 48 h. In the presence of PrC-210, muscle cell mitochondrial cytochrome C release was equivalent to 0 h controls, with profound reductions in the caspase-3,7 apoptotic marker that correlated with limb histology. PrC-210 conferred complete prevention of ROS-induced mitochondrial lysis in vitro, as measured by cytochrome C release. We conclude that the addition of 30 mM PrC210 to UW Solution conferred the most consistent reduction in CI limb damage, and it warrants further investigation for clinical application in the VCA setting.

Perforator Dissection Porcine Abdominal Model: A Novel Simulator to Improve Microsurgical Training.

BACKGROUND: Perforator dissection and flap elevation are routinely performed for microsurgical reconstruction; however, there is a steep learning curve to mastering these technical skills. Though live porcine models have been utilized as microsurgical training models, significant drawbacks limit their use. We recently developed a latex-perfused, nonliving, porcine abdomen perforator dissection simulation and described its anatomic similarity to the human deep inferior epigastric artery flap. The purpose was to assess the change in resident confidence in performing key operative steps of flap elevation and perforator dissection and obtain feedback on model realism and utility. METHODS: Seventeen plastic and reconstructive surgery resident physicians (postgraduate years 1-6) at a single institution participated in a perforator dissection session utilizing the simulation model. Each resident completed pre- and postactivity surveys to assess interval change in confidence in operating. The postactivity survey also asked residents to answer questions regarding their perception of the model's anatomic and surgical realism and utility in microsurgical training. RESULTS: Following a practice session using the latex-perfused, nonliving porcine abdomen, resident confidence was significantly increased in performing all key operative steps and the procedure overall (p = 0.001). All residents (n = 17, 100%) believed the model would improve "trainees' ability to perform perforator dissection in the operating room." Perforator, fascial, and pedicle anatomy were reported to be "Very" similar to human anatomy, with a median Likert score (MLS) of 4. Additionally, six out of the eight surgical steps were noted to be "Very" realistic, with only "Flap Design" and "Fascial Closure" found to be "Moderately" realistic with an MLS of 3. CONCLUSION: The latex-infused porcine abdominal model is a novel, realistic simulation for microsurgical trainee perforator dissection practice. This model offers a suitable substitute for perforator dissection practice, as its implementation within a microsurgery training course improves resident comfort and confidence.

Trigeminal or peripheral nerve stimulation improves functional outcomes of nerve recovery in a rodent forelimb gap repair model.

BACKGROUND: The hypothesis of this study was that trigeminal nerve stimulation (TNS) or peripheral nerve stimulation (PNS) could improve functional outcomes of peripheral nerve injury in a rat forelimb model when compared to control rats not receiving electrical stimulation (ES). While PNS is known to improve outcomes after nerve surgery, the role of TNS has not been explored. METHODS: Lewis rats were trained to perform a reach and grasp task before receiving a 2 mm gap repair of the ulnar and median nerves and randomized into four treatment groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with PNS, and (4) nerve injury with TNS. Functional motor (median pull force and percent success in motor task) and sensory metrics (forelimb paw withdrawal thresholds) were collected both pre-injury and throughout rehabilitation. Nerves stained using Gomori's trichrome were assessed quantitatively and qualitatively. RESULTS: The sham ES group did not recover their pre-injury baseline functional outcomes. In contrast, the TNS and PNS groups fully recovered following injury, with no difference in functional outcomes between the pre-injury baseline and the final week of rehabilitation (P > 0.05, all). Histomorphology results demonstrated no quantitative difference, but qualitative differences in architecture were evident. CONCLUSIONS: Electrical stimulation of the trigeminal nerve or the injured nerve improved the functional outcomes of nerve regeneration in rodents. Histomorphology results of nerves from the TNS group support the proposed central mechanisms. This is an important step in translating this therapy as an adjunct, non-invasive treatment for high, mixed nerve injuries in humans.

Latex-Infused Porcine Abdominal Model: A Novel Microsurgery Simulator for Deep Inferior Epigastric Perforator Dissection.

BACKGROUND: Perforator dissection and flap elevation are routinely performed for microsurgical reconstruction; however, there is a steep learning curve to mastering these technical skills. Though live porcine models have been utilized as a microsurgical training model, there are significant drawbacks that limit their use, including cost, limited ability for repetition, and obstacles associated with animal care. Here we describe the creation of a novel perforator dissection model using latex augmented non-living porcine abdominal walls. We provide anatomic measurements that demonstrate valuable similarities and differences to human anatomy to maximize microsurgical trainee practice. METHODS: Six latex-infused porcine abdomens were dissected based on the deep cranial epigastric artery (DCEA). Dissection was centered over the abdominal wall mid-segment between the second and fourth nipple line. Dissection steps included exposure of lateral and medial row perforators, incision of anterior rectus sheath with perforator dissection, and dissection of DCEA pedicle. DCEA pedicle and perforator measurements were compared with deep inferior epigastric artery (DIEA) data in the literature. RESULTS: An average of seven perforators were consistently identified within each flap. Assembly of the model was performed quickly and allowed for two training sessions per specimen. Porcine abdominal walls demonstrate similar DCEA pedicle (2.6 ± 0.21 mm) and perforator (1.0 ± 0.18 mm) size compared with a human's DIEA (2.7 ± 0.27 mm, 1.1 ± 0.85 mm). CONCLUSION: The latex-infused porcine abdominal model is a novel, realistic simulation for perforator dissection practice for microsurgical trainees. Impact on resident comfort and confidence within a microsurgical training course is forthcoming.

A framework for understanding prosthetic embodiment for the plastic surgeon.

Plastic surgeons play a critical role in the management of amputations and are uniquely positioned to improve the lives and functional abilities of patients with limb loss. The embodiment of a prosthesis describes how effectively it replaces a missing limb and is an important aspect of patient care. Despite its importance, the current prosthetics literature lacks a formal definition of embodiment, and descriptions are often vague or incomplete. In this narrative review, we assess the current literature on prosthetic embodiment to explore the main mechanisms of embodiment and how each allows a prosthesis to interface with the human body. In doing so, we provide a comprehensive, holistic framework for understanding this concept.

Evaluation of a Full-Time Microsurgeon Educator on Resident Training, Research Collaboration, and Grant Funding.

BACKGROUND: The value of a fully trained microsurgeon dedicated to a laboratory setting at an academic institution is largely unknown. Microsurgery training lacks a national standard despite its highly complicated nature. Our study aims to evaluate the impact of a single laboratory-dedicated microsurgeon on the microsurgical training of integrated plastic surgery residents and collaborative efforts in research. METHOD: We devised a three-faceted microsurgical training curriculum, including a collaborative multi-institutional microsurgery course, novel high-fidelity simulator models, and a dedicated microsurgeon. We cataloged grant funding achieved through support to other divisions' protocols. Time, in hours, spent on training and the number of anastomoses completed with the microsurgical educator in a laboratory setting over a 4-year period (2017-2021) were evaluated. Resident independence scores were collected from attending microsurgeons to quantify the translation of microsurgical training. RESULTS: Purchasing and maintenance costs of rats in our rodent facility decreased by $16,533.60 as 198 rats were replaced by our models. The residents who participated in our novel microsurgical training program were able to independently perform anastomoses in the OR by their postgraduate year 6. Additionally, the surgical support offered by our laboratory-dedicated microsurgeon led to a total of $24,171,921 in grant funding between 2017 and 2020. CONCLUSION: Hiring an expert microsurgical educator to train residents in a laboratory has proved promising in accelerating microsurgical mastery. Novel training modules, alternatives to animal models, save resources in housing and animal costs. The addition of a research-oriented-microsurgeon has improved collaborative efforts to advance a range of surgical fields.

Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications.

BACKGROUND: Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory centers via projections of the vagus nerve to the solitary tract nucleus. Currently, there is not an established large animal model that facilitates detailed mechanistic studies exploring how VNS impacts the function of the CNS, especially during complex behaviors requiring motor action and decision making. METHODS: We describe the anatomical organization, surgical methodology to implant VNS electrodes on the left gagus nerve and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we describe the results of pilot experiments in a small number of NHPs to demonstrate how this preparation might be used in an animal model capable of performing complex motor and decision making tasks. RESULTS: VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. CONCLUSIONS: We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory.

Efficacy of bone stimulators in large-animal models and humans may be limited by weak electric fields reaching fracture.

Noninvasive electronic bone growth stimulators (EBGSs) have been in clinical use for decades. However, systematic reviews show inconsistent and limited clinical efficacy. Further, noninvasive EBGS studies in small animals, where the stimulation electrode is closer to the fracture site, have shown promising efficacy, which has not translated to large animals or humans. We propose that this is due to the weaker electric fields reaching the fracture site when scaling from small animals to large animals and humans. To address this gap, we measured the electric field strength reaching the bone during noninvasive EBGS therapy in human and sheep cadaver legs and in finite element method (FEM) models of human and sheep legs. During application of 1100 V/m with an external EBGS, only 21 V/m reached the fracture site in humans. Substantially weaker electric fields reached the fracture site during the later stages of healing and at increased bone depths. To augment the electric field strength reaching the fracture site during noninvasive EBGS therapy, we introduced the Injectrode, an injectable electrode that spans the distance between the bone and subcutaneous tissue. Our study lays the groundwork to improve the efficacy of noninvasive EBGSs by increasing the electric field strength reaching the fracture site.

A C-arm photon counting CT prototype with volumetric coverage using multi-sweep step-and-shoot acquisitions.

Objective.Existing clinical C-arm interventional systems use scintillator-based energy-integrating flat panel detectors (FPDs) to generate cone-beam CT (CBCT) images. Despite its volumetric coverage, FPD-CBCT does not provide sufficient low-contrast detectability desired for certain interventional procedures. The purpose of this work was to develop a C-arm photon counting detector (PCD) CT system with a step-and-shoot data acquisition method to further improve the tomographic imaging performance of interventional systems.Approach.As a proof-of-concept, a cadmium telluride-based 51 cm × 0.6 cm PCD was mounted in front of a FPD in an Artis Zee biplane system. A total of 10 C-arm sweeps (5 forward and 5 backward) were prescribed. A motorized patient table prototype was synchronized with the C-arm system such that it translates the object by a designated distance during the sub-second rest time in between gantry sweeps. To evaluate whether this multi-sweep step-and-shoot acquisition strategy can generate high-quality and volumetric PCD-CT images without geometric distortion artifacts, experiments were performed using physical phantoms, a human cadaver head, and anin vivoswine subject. Comparison with FPD-CT was made under matched narrow beam collimation and radiation dose conditions.Main results.Compared with FPD-CT images, PCD-CT images had lower noise and improved visualization of low-contrast lesion models, as well as improved visibility of small iodinated blood vessels. Fine structures were visualized more clearly by the PCD-CT than the highest-available resolution provided by FPD-CBCT and MDCT. No perceivable geometric distortion artifacts were observed in the multi-planar PCD-CT images.Significance.This work is the first demonstration of the feasibility of high-quality and multi-planar (volumetric) PCD-CT imaging with a rotating C-arm gantry.

Electrical Stimulation of Acute Fractures: A Narrative Review of Stimulation Protocols and Device Specifications.

Orthopedic fractures have a significant impact on patients in the form of economic loss and functional impairment. Beyond the standard methods of reduction and fixation, one adjunct that has been explored since the late 1970s is electrical stimulation. Despite robust evidence for efficacy in the preclinical arena, human trials have mixed results, and this technology is not widely accepted. The purpose of this review is to examine the body of literature supporting electrical stimulation for the purpose of fracture healing in humans with an emphasis on device specifications and stimulation protocols and delineate a minimum reporting checklist for future studies of this type. We have isolated 12 studies that pertain to the administration of electrical stimulation for the purpose of augmenting fracture healing in humans. Of these, one was a direct current electrical stimulation study. Six studies utilized pulsed electromagnetic field therapy and five used capacitive coupling. When examining these studies, the device specifications were heterogenous and often incomplete in what they reported, which rendered studies unrepeatable. The stimulation protocols also varied greatly study to study. To demonstrate efficacy of electrical stimulation for fractures, the authors recommend isolating a fracture type that is prone to nonunion to maximize the electrical stimulation effect, a homogenous study population so as to not dilute the effect of electrical stimulation, and increasing scientific rigor in the form of pre-registration, blinding, and sham controls. Finally, we introduce the critical components of minimum device specification reporting for repeatability of studies of this type.

Diversity Drives Innovation: The Impact of Female-Driven Publications.

BACKGROUND: Gender disparities are pervasive in academic plastic surgery. Previous research demonstrates articles authored by women receive fewer citations than those written by men, suggesting the presence of implicit gender bias. OBJECTIVES: The aim of this study was to describe current citation trends in plastic surgery literature and assess gender bias. The expectation was that women would be cited less frequently than their male peers. METHODS: Articles published between 2017 and 2019 were collected from 8 representative plastic surgery journals stratified by impact factor. Names of primary and senior authors of the 50 most cited articles per year per journal were collected and author gender was determined via online database and internet search. The median numbers of citations by primary and senior author gender were compared by Kruskal-Wallis test. RESULTS: Among 1167 articles, women wrote 27.3% as primary author and 18% as senior author. Women-authored articles were cited as often as those authored by men (P > 0.05) across all journal tiers. Articles with a female primary and male senior author had significantly more citations than articles with a male primary author (P = 0.038). CONCLUSIONS: No implicit gender bias was identified in citation trends, a finding unique to plastic surgery. Women primary authors are cited more often than male primary authors despite women comprising a small fraction of authorship overall. Additionally, variegated authorship pairings outperformed homogeneous ones. Therefore, increasing gender diversity within plastic surgery academia remains critical.

Local Environment Induces Differential Gene Expression in Regenerating Nerves.

INTRODUCTION: Approximately 80% of amputations are complicated by neuromas. Methods for neuroma management include nerve translocation into bone and implantation into skeletal muscle grafts, which have also facilitated the development of regenerative neural interfaces to enable fixation of prosthetics with motor and sensory feedback. However, molecular-level differences between nerves in these environments have not been investigated. This study aimed to elucidate the physiology of regenerating nerves in different settings by assessing gene expression. MATERIALS AND METHODS: New Zealand white rabbits underwent transfemoral amputation with sciatic nerve transposition into the femur or tacked to skeletal muscle. At 5 wk, ribonucleic acid (RNA) sequencing of samples of distal nerve terminating in bone or muscle and nerve of the contralateral limb (control) identified differentially expressed genes (DEGs) and biochemical pathways (α = 0.05). RESULTS: Three samples of nerve housed in bone, four of nerve tacked to muscle, and seven naïve controls were analyzed. Relative to controls, nerve housed in bone had little within-group variation and 13,028 DEGs, and nerve tacked to muscle had dramatic within-group variation and 12,811 DEGs. These samples upregulated the following pathways: lysosome, phagosome, antigen processing/presentation, and cell adhesion molecule. Relative to nerve housed in bone, nerve tacked to muscle had 12,526 DEGs, demonstrating upregulation of pathways of B-cell receptor signaling, focal adhesion, natural killer-cell mediated cytotoxicity, leukocyte transendothelial migration, and extracellular matrix-receptor interactions. CONCLUSIONS: Nerve housed in bone has a more predictable molecular profile than does nerve tacked to muscle. Thus, the intramedullary canal may provide a more reliable setting for neuroma prevention and neural interfacing.

The Effect of Tension on Gene Expression in Primary Nerve Repair via the Epineural Suture Technique.

INTRODUCTION: The precise mechanism through which excessive tension confers poor outcomes in nerve gap repair is yet to be elucidated. Furthermore, the effect of tension on gene expression in regenerating nerves has not been characterized. This study investigated differential gene expression in transected nerves repaired under high and minimal tension. METHODS: Male Lewis rats underwent right sciatic nerve transection with either minimal-tension or high-tension repair. Fourteen weeks postoperatively, segments of the right sciatic nerves were harvested along with equal-length segments from the contralateral, healthy nerve to serve as internal controls (naïve nerve). Differentially expressed genes (DEGs) and differentially regulated biochemical pathways between the samples were identified. RESULTS: Seventeen animals were studied. The gene expression profiles of naïve nerve and minimal-tension repair demonstrated minimal within-group variation, whereas that of high-tension repair demonstrated heterogeneity. Relative to naïve nerve, high-tension repair samples had 4276 DEGs (1941 upregulated and 2335 downregulated) and minimal-tension repair samples had 3305 DEGs (1479 upregulated and 1826 downregulated). High-tension repair samples had 360 DEGs relative to minimal-tension repair samples (68 upregulated and 292 downregulated). Upregulated biological pathways in all repaired nerves included steroid biosynthesis, extracellular matrix-receptor interaction, and ferroptosis. Finally, upregulated pathways in high-tension repair samples relative to minimal-tension repair samples included tumor necrosis factor signaling, interleukin-17 signaling, cytokine-cytokine receptor interaction, and mitogen-activated protein kinase signaling. CONCLUSIONS: The improved outcomes achieved with minimal-tension nerve repair may take root in a favorable gene expression profile. Future elucidation of biochemical pathways in nerve regeneration may identify potential therapeutic targets to optimize primary nerve repair outcomes.

Clinical Basis for Creating an Osseointegrated Neural Interface.

As technology continues to improve within the neuroprosthetic landscape, there has been a paradigm shift in the approach to amputation and surgical implementation of haptic neural prosthesis for limb restoration. The Osseointegrated Neural Interface (ONI) is a proposed solution involving the transposition of terminal nerves into the medullary canal of long bones. This design combines concepts of neuroma formation and prevention with osseointegration to provide a stable environment for conduction of neural signals for sophisticated prosthetic control. While this concept has previously been explored in animal models, it has yet to be explored in humans. This anatomic study used three upper limb and three lower limb cadavers to assess the clinical feasibility of creating an ONI in humans. Anatomical measurement of the major peripheral nerves- circumference, length, and depth- were performed as they are critical for electrode design and rerouting of the nerves into the long bones. CT imaging was used for morphologic bone evaluation and virtual implantation of two osseointegrated implants were performed to assess the amount of residual medullary space available for housing the neural interfacing hardware. Use of a small stem osseointegrated implant was found to reduce bone removal and provide more intramedullary space than a traditional implant; however, the higher the amputation site, the less medullary space was available regardless of implant type. Thus the stability of the endoprosthesis must be maximized while still maintaining enough residual space for the interface components. The results from this study provide an anatomic basis required for establishing a clinically applicable ONI in humans. They may serve as a guide for surgical implementation of an osseointegrated endoprosthesis with intramedullary electrodes for prosthetic control.