Faculty Bibliography

Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Implant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.

OBJECTIVES/OBJECTIVE:To assess surgical instrument usage in cleft lip (CL) and cleft palate (CP) surgery and create an optimized surgical tray with an associated cost-savings analysis. DESIGN/METHODS:Prospective, observational study. SETTING/METHODS:Single institution, 6-month prospective review. PATIENTS/PARTICIPANTS/METHODS:A total of 10 primary CL surgeries and 10 primary CP surgeries were included in this study. INTERVENTION/METHODS:Complete lists of surgical instruments utilized in CL and CP surgeries were collected. UNLABELLED:Utilization fractions (UFs) were calculated as the percentages of average used instruments to averaged opened instruments per case. New optimized CL and CP surgical trays were idealized by removing instruments not used in at least 20% of cases, and a cost analysis was performed to identify potential savings. Calculation of annual potential savings was also conducted based on institutional caseload. RESULTS:The average instrument UFs were 26.0% for CL and 22.6% for CP. The estimated costs were $33.15 to $290.29 for the original CL surgical tray and $10.20 to $63.80 for the optimized tray. For CP, the original tray's cost was estimated at $38.25 to $319.00, and the optimized tray at $9.18 to $57.42. This demonstrates a cost reduction of $22.95 to $226.49 for CL and $29.07 to 261.58 for CP. CONCLUSIONS:The idealized surgical instrument tray could contribute to reducing healthcare expenditures and promoting operating room efficiency, patient safety, and environmentally friendlier operating theaters.

Biomimetics is the science of imitating nature's designs and processes to create innovative solutions for various fields, including dentistry and craniofacial reconstruction. In these areas, biomimetics involves drawing inspiration from living organisms/systems to develop new materials, techniques, and devices that closely resemble natural tissue structures and enhance functionality. This field has successfully demonstrated its potential to revolutionize craniofacial procedures, significantly improving patient outcomes. In dentistry, biomimetics offers exciting possibilities for the advancement of new dental materials, restorative techniques, and regenerative potential. By analyzing the structure/composition of natural teeth and the surrounding tissues, researchers have developed restorative materials that mimic the properties of teeth, as well as regenerative techniques that might assist in repairing enamel, dentin, pulp, cementum, periodontal ligament, and bone. In craniofacial reconstruction, biomimetics plays a vital role in developing innovative solutions for facial trauma, congenital defects, and various conditions affecting the maxillofacial region. By studying the intricate composition and mechanical properties of the skull and facial bones, clinicians and engineers have been able to replicate natural structures leveraging computer-aided design and manufacturing (CAD/CAM) and 3D printing. This has allowed for the creation of patient-specific scaffolds, implants, and prostheses that accurately fit a patient's anatomy. This review highlights the current evidence on the application of biomimetics in the fields of dentistry and craniofacial reconstruction.

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease-activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain-selective activity-based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with dextran sulfate sodium-induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed field asymmetric waveform ion mobility spectrometry-facilitated quantitative proteomics and N-terminomics analyses on naïve and inflamed colon tissue from wild-type and legumain-deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer.

Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR₂, encoded by F2RL1) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR₂ is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR₂ from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR₂ on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR₂ inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR₂ activation. We report that F2RL1 was overexpressed in human oral cancers and cancer cell lines. Deletion of F2RL1 on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR₂ at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of F2RL1 on cancer cells or F2rl1 on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR₂ on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR₂ antagonist provide increased antinociception and improved oral function compared to free drug.

GENERAL PURPOSE/OBJECTIVE:To review the role of nutrition and high-quality dietary protein intake in creating healthy granulation tissue and optimize wound healing in patients with chronic wounds. TARGET AUDIENCE/BACKGROUND:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES/OBJECTIVE:After participating in this educational activity, the participant will:1. Summarize the structure and composition of proteins. 2. Specify the role of proteins in generating healthy granulation tissue and wound healing. 3. Explain the physiologic pathways involved in the wound healing process. 4. Describe evidence-based interventions to support nutrition in wound healing.

BACKGROUND:Overhanging pannus may be detrimental to ambulation, urination, sexual function, and social well-being. Massive weight loss patients often have high residual body mass index (BMI) and comorbidities presenting a unique challenge in panniculectomy patient selection. This study aims to better characterize the role of BMI in postoperative complications following panniculectomy. METHODS:A meta-analysis attempted to assess the impact of BMI on complications following panniculectomy. Cochrane Q and I2 test statistics measured study heterogeneity, with subsequent random effects meta-regression investigating these results. After this, all panniculectomy patients in the National Surgical Quality Improvement Program database in the years 2007 to 2019 were analyzed. Univariate and multivariable tests assessed the relative role of BMI on 30-day postoperative complications. RESULTS:Thirty-four studies satisfied inclusion criteria, revealing very high heterogeneity (Cochrane Q = 2453.3; I2 = 99.1%), precluding further meta-analysis results. Receiver operating characteristic curves demonstrated BMI was a significant predictor of both all causes (area under the curve, 0.64; 95% CI, 0.62 to 0.66) and wound complications (area under the curve, 0.66; 95% CI, 0.63 to 0.69). BMI remained significant following multivariable regression analyses. Restricted cubic spines demonstrated marginal increases in complication incidence above 33.2 and 35 kg/m 2 for all-cause and wound complications, respectively. CONCLUSIONS:Reported literature regarding postoperative complications in panniculectomy patients is highly heterogeneous and may limit evidence-based care. Complication incidence positively correlated with BMI, although the receiver operating characteristic curve demonstrated its limitations as the sole predictive variable. Furthermore, restricted cubic splines demonstrated diminishing marginal predictive capacity of BMI for incremental increases in BMIs above 33.2 to 35 kg/m 2 . These findings support a reevaluation of the role of BMI cutoffs in panniculectomy patient selection.

PURPOSE/UNASSIGNED:High quality data regarding long-term clinical and patient-reported outcomes (PROs) of genital gender-affirming surgery (GGAS) are lacking, and transgender and non-binary (TGNB) community voices have not historically been included in research development. These factors limit the utility of current research for guiding patients, clinicians, payers, and other GGAS stakeholders in decision-making. The Transgender and Non-Binary Surgery (TRANS) Registry has been developed to meet the needs of GGAS stakeholders and address limitations of traditional GGAS research. METHODS/UNASSIGNED:Development of the TRANS Registry occurred over several developmental phases beginning in May 2019 to present. Stakeholder engagement was performed throughout these phases, including: determination of key clinical outcomes and PROs, creation and implementation of data collection tools within the electronic health record (EHR), and development of centralized registry infrastructure. RESULTS/UNASSIGNED:The TRANS Registry is a prospective observational registry of individuals seeking vaginoplasty and vulvoplasty. The EHR-enabled infrastructure allows patients and clinicians to contribute longitudinal outcomes data to the TRANS Registry. We describe our community engaged approach to designing the TRANS Registry, including lessons learned, challenges, and future directions. CONCLUSIONS/UNASSIGNED:The TRANS Registry is the first multicenter initiative to prospectively track the health of individuals seeking vaginoplasty and vulvoplasty using EHR-enabled methods, engaging TGNB community members and clinicians as partners in the process. This process may be used as a model for registry development in other emerging fields where high-quality longitudinal outcomes data are needed.

BACKGROUND:Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS/METHODS:Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS:A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS:Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.