Faculty Bibliography

Since three-dimensional (3D) bioprinting has emerged, it has continuously to evolved as a revolutionary technology in surgery, offering new paradigms for reconstructive and regenerative medical applications. This review highlights the integration of 3D printing, specifically bioprinting, across several surgical disciplines over the last five years. The methods employed encompass a review of recent literature focusing on innovations and applications of 3D-bioprinted tissues and/or organs. The findings reveal significant advances in the creation of complex, customized, multi-tissue constructs that mimic natural tissue characteristics, which are crucial for surgical interventions and patient-specific treatments. Despite the technological advances, the paper introduces and discusses several challenges that remain, such as the vascularization of bioprinted tissues, integration with the host tissue, and the long-term viability of bioprinted organs. The review concludes that while 3D bioprinting holds substantial promise for transforming surgical practices and enhancing patient outcomes, ongoing research, development, and a clear regulatory framework are essential to fully realize potential future clinical applications.

The use of porcine-derived collagen membranes (PDCM) to improve intraoral soft tissue rehabilitation remains under investigation. Different degrees of crosslinking have yielded differences in resorption time and inflammation surrounding collagen membranes. The aim of this study was to evaluate the in vivo performance of bilayered PDCMs with varying degrees of crosslinking for the regeneration of oral soft tissue defects. Bilateral split-thickness oral mucosa defects were created in mandibles of beagles (n=17) and assigned to one of the following: bilayer PDCM (high crosslinking porcine dermis in sheet form-H-xlink) and (low crosslinking porcine dermis in sheet form-L-xlink), bilayer PDCM (non-crosslinked predicate collagen membrane in spongy form-Ctrl), or negative control (Sham) and compared with positive control (unoperated). Animals were euthanized after 4-, 8-, or 12-weeks of healing to evaluate soft tissue regeneration and remodeling through histomorphometric analyses. H-xlink membranes presented delayed healing with a poorly developed epithelial layer (analogous to the sham group) across time points. Relative to Ctrl at 8 and 12 weeks, defects treated with H-xlink presented no difference in semiquantitative scores ( P > 0.05), while L-xlink exhibited greater healing ( P = 0.042, P = 0.043, at 8 and 12 weeks, respectively). Relative to positive control, L-xlink exhibited similar healing at 8 weeks and greater healing at 12 weeks ( P = 0.037) with a well-developed epithelial layer. Overall, groups treated with L-xlink presented with greater healing relative to the positive control after 12 weeks of healing and may serve as an alternative to autologous grafts for intraoral soft tissue regeneration.

OBJECTIVE:To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS:Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS:Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS:Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Inflammatory epithelial diseases are spurred by the concomitant dysregulation of immune and epithelial cells. How these two dysregulated cellular compartments simultaneously sustain their heightened metabolic demands is unclear. Single-cell and spatial transcriptomics (ST), along with immunofluorescence, revealed that hypoxia-inducible factor 1α (HIF1α), downstream of IL-17 signaling, drove psoriatic epithelial remodeling. Blocking HIF1α in human psoriatic lesions ex vivo impaired glycolysis and phenocopied anti-IL-17 therapy. In a murine model of skin inflammation, epidermal-specific loss of HIF1α or its target gene, glucose transporter 1, ameliorated epidermal, immune, vascular, and neuronal pathology. Mechanistically, glycolysis autonomously fueled epithelial pathology and enhanced lactate production, which augmented the γδ T17 cell response. RORγt-driven genetic deletion or pharmacological inhibition of either lactate-producing enzymes or lactate transporters attenuated epithelial pathology and IL-17A expression in vivo. Our findings identify a metabolic hierarchy between epithelial and immune compartments and the consequent coordination of metabolic processes that sustain inflammatory disease.

BACKGROUND:Velopharyngeal insufficiency (VPI) is a condition characterized by incomplete separation of the oral and nasal cavities during speech production, thereby leading to speech abnormalities and audible nasal emissions. Subsequently, this adversely impacts communication and potentially interpersonal social interactions. Autologous fat grafting (AFG) to the velopharynx, a minimally invasive technique, aims to improve oronasal separation by providing bulk and advancing the posterior pharyngeal wall toward the soft palate. Despite its potential, the relative novelty of AFG in treating VPI has resulted in reporting of inconsistent indications, varied surgical techniques, and mixed outcomes across existing literature. METHODS:This systemic review examined the evidence of AFG for VPI treatment over the past decade (2013-2023). A thorough search across five electronic databases yielded 233 studies, with 20 meeting the inclusion criteria (e.g., utilized fat injection as their selected VPI treatment, conducted study in human subjects, did not perform additional surgical procedure at time of fat injection). Selected studies encompassed patient and surgical intervention characteristics, perceptual speech assessment (PSA) scores, gap sizes, nasalance measurements, and complications. RESULTS:The majority of patients had a prior cleft palate diagnosis (78.2%), in which nasoendoscopy was the prevalent method for visualizing the velopharyngeal port defect. Fat harvesting predominantly occurred from the abdomen (64.3%), with an average injection volume of 6.3 mL across studies. PSA and subjective gap size scores were consistently higher preoperatively than postoperatively. PSA score analysis from seven studies revealed significant and sustained improvements postoperatively. Gap size score analysis from four studies demonstrated similar preoperative and postoperative differences. Complications were reported in 17 studies, yielding a 2.7% summative complication rate among 594 cases. CONCLUSIONS:Autologous fat grafting has emerged as a minimally invasive, safe, and effective treatment for mild to moderate VPI. However, challenges remain because of variability in patient selection criteria, diagnostic modalities, and outcome measurements. This review underscores the need for randomized control trials to directly compare AFG with standard-of-care surgical interventions, providing more conclusive evidence of its clinical efficacy.

BACKGROUND:Breast reduction mammaplasty is among the most common procedures in plastic surgery, with a 1% to 7% postoperative hematoma incidence reported. Tranexamic acid (TXA) has been shown to reduce perioperative bleeding and need for transfusion when administered intravenously or topically, but it remains underused in plastic surgery. This study aims to investigate whether topical administration of topical TXA reduces postoperative hematoma following breast reduction mammaplasty. METHODS:A double-blind randomized controlled trial of 98 patients (196 breasts) undergoing bilateral primary reduction mammaplasty at a single academic institution was performed. Patients were used as internal matched controls, with one breast randomized to receive 1000 mg of topical TXA before closure, and the other receiving saline. All members of the surgical team and the patient were blinded as to which breast received the study drug. Postoperative complications, including hematoma within 30 days of surgery, drain outputs, and duration of drain use, were compared between treatment and placebo breasts. RESULTS:The overall hematoma rate was 1.5%. There was no significant association between application of TXA and development of a hematoma ( P = 0.56) or other complications. The hematoma rate of patients enrolled in the trial was similar to the overall rate of hematoma during the study period (1.5% versus 2.4%; P = 0.511). In a multivariate model, TXA was not significantly associated with differences in drain output after controlling for resection weight, age, and duration of drain use ( P = 0.799). No adverse effects or thromboembolic events from TXA were observed. CONCLUSION:Topical application of TXA does not decrease the incidence of hematoma following reduction mammaplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, I.

STUDY DESIGN/UNASSIGNED:Retrospective observational study. OBJECTIVE/UNASSIGNED:This study analyzes the epidemiology of pediatric Le Fort fractures and assesses the incidence of concomitant injuries and acute-level hospital course using the largest, national pediatric trauma database to date. METHODS/UNASSIGNED:Pediatric midface and Le Fort fractures from 2016-2019 were identified in the National Trauma Data Bank. Descriptive analyses of Le Fort compared to non-Le Fort midface fractures were performed. Multivariable regression assessed whether Le Fort fractures were risk factors for ICU admission, intracranial injury, cervical spine (C-spine) fracture, tracheostomy, and mortality. RESULTS/UNASSIGNED:< 0.001). Incidence of all the above increased with higher-grade Le Fort fractures. Le Fort III fractures had higher rates of mortality than non-Le Fort midface fractures (7.6% vs 3.2%). Multivariable regression showed that all Le Fort patterns were independent risk factors for tracheostomy and ICU admission, but only Le Fort I for C-spine fractures. CONCLUSIONS/UNASSIGNED:The incidence of Le Fort fractures appears to increase with age. Higher category Le Fort fractures are associated with greater morbidity.

OBJECTIVE:Previous work identified an association between genetics and neurodevelopmental delays in patients with nonsyndromic craniosynostosis. The authors investigated the role of genetic mutations on behavioral outcomes of patients with treated sagittal synostosis. METHODS:Parents of children aged 6-18 years with surgically corrected sagittal synostosis were recruited to complete the Child Behavioral Checklist (overall behavioral problems), Conners 3rd Edition-Parent (attention-deficit/hyperactivity disorder), Social Responsiveness Scale 2nd Edition (autism spectrum disorder [ASD]), and Behavior Rating Inventory of Executive Function 2nd Edition (executive function). Genomic analysis was completed, and patients were identified if they had mutations in high probability of loss of function intolerant (pLI) genes (high pLI vs nonhigh pLI). Genetic burden was assessed relative to controls. Multivariate linear regression determined the association of mutations in high pLI genes with behavioral scores, while controlling for sociodemographic factors, age at surgery, surgery type, and IQ. RESULTS:Sixteen of 45 patients were in the high pLI group. There were no differences between the groups in terms of sociodemographic factors. A greater proportion of children in the high pLI group scored at or above borderline clinical levels for aggression (18.8% vs 0.0%, p = 0.05) and externalizing problems (31.3% vs 3.7%, p = 0.02). Among children in the nonhigh pLI group, older age at surgery was associated with worse scores on the rule-breaking, aggression, and externalizing problems domains and four out of five ASD domains. CONCLUSIONS:Children with treated nonsyndromic sagittal synostosis and mutations in high pLI genes had worse behavioral problems in externalizing behaviors and aggression, whereas older age at surgery was a significant predictor of worse behavioral outcomes in patients without mutations in high pLI genes.

BACKGROUND/UNASSIGNED:This study investigates whether open distal radius fractures (ODRFs) treated after 24 hours from time of injury have an increased risk of infection or overall complication profile compared with those treated within 24 hours. METHODS/UNASSIGNED:Retrospective review was performed of all patients treated for ODRF over a 6-year period at a single large academic institution. Postoperative complications included surgical site infections, need for revision irrigation and debridement, delayed soft tissue healing, loss of reduction, nonunion, and malunion. RESULTS/UNASSIGNED:One-hundred twenty patients were treated for ODRF. Mean (SD) age at time of injury was 59.92 (17.68) years. Twenty patients (16.7%) had postoperative complications. Regarding mechanism of injury, 78 (65.0%) had a low-energy and 42 (35.0%) had a high-energy injury. Age and fracture grade were not significant factors. Mean (SD) open wound size was 1.18 (1.57) cm. Mean (SD) time from injury presentation to the emergency department (ED) and first dose of intravenous antibiotics was 3.07 (4.05) hours and mean (SD) time from presentation to the ED and operative treatment was 11.90 (6.59) hours, which did not show a significant association with postoperative complications. Twenty-four patients (20.0%) were treated greater than 24 hours after presentation to the ED, which was not significantly distinct from those treated within 24 hours. CONCLUSION/UNASSIGNED:Patients with ODRFs treated after 24 hours were not associated with a greater risk of postoperative complications. Factors including age, energy and mechanism of injury, and fracture grade did not alter outcome in any statistically significant manner. LEVEL OF EVIDENCE/UNASSIGNED:Level IV.