Faculty Bibliography

This study compares outcomes of patients with Lisfranc injuries treated with screw only fixation constructs to those treated with dorsal plate and screw constructs. Seventy patients who underwent surgical treatment for acute Lisfranc injury without arthrodesis and minimum 6-month (mean >1-year) follow-up were identified. Demographics, surgical information, and radiographic imaging were reviewed. Cost data were compared. The primary outcome measure was the American Orthopedic Foot and Ankle Surgery (AOFAS) midfoot score. Univariate analysis through independent sample t tests, Mann-Whitney U, and chi-squared compared the populations. Twenty-three (33%) patients were treated with plate constructs and 47 (67%) with screw only fixation. The plate group was older (49 ± 18 vs 40 ± 16 years, p = .029). More screw constructs treated isolated medial column injuries compared to plate constructs (92% vs 65%, p = .006). At latest follow-up (mean 14 ± 13 months), all tarsometatarsal joints were aligned. There was no difference in AOFAS midfoot scores. Plate patients experienced longer operations (131 ± 70 vs 75 ± 31 minutes, p < .001) and tourniquet time (101 ± 41 vs 69 ± 25 minutes, p = .001). Plate constructs were more expensive than screw ($2.3X ± $2.3X vs $X ± $0.4X, p < .001) ($X is the mean cost of screws alone). Plate patients had a higher incidence of wound complications (13% vs 0%, p = .012). Treatment of Lisfranc fracture dislocation injuries with screws only demonstrated a higher value procedure as similar outcomes were found amidst lower implant costs. Screw only fixation required a shorter operative and tourniquet time with less frequent wound complications. Screw only fixations proved mechanically sound enough to achieve goals of repair without inferior outcomes.

Blockchain technology has attracted substantial interest in recent years, most notably for its effect on global economics through the advent of cryptocurrency. Within the health care domain, blockchain technology has been actively explored as a tool for improving personal health data management, medical device security, and clinical trial management. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, integration of blockchain technologies within plastic surgery is in its infancy. Recent advances and mainstream adoption of blockchain are gaining momentum and have shown significant promise for improving patient care and information management. In this article, the authors explain what defines a blockchain and discuss its history and potential applications in plastic surgery. Existing evidence suggests that blockchain can enable patient-centered data management, improve privacy, and provide additional safeguards against human error. Integration of blockchain technology into clinical practice requires further research and development to demonstrate its safety and efficacy for patients and providers.

Although robotic surgery has been routinely established in other surgical disciplines, robotic technologies have been less readily adopted in plastic surgery. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, most reconstructive procedures, including microsurgery, have continued to necessitate an open approach. Recent advances in robotics and artificial intelligence, however, are gaining momentum and have shown significant promise to improve patient care in plastic surgery. These next-generation surgical robots have the potential to enable surgeons to perform complex procedures with greater precision, flexibility, and control than previously possible with conventional techniques. Successful integration of robotic technologies into clinical practice in plastic surgery requires achieving key milestones, including implementing appropriate surgical education and garnering patient trust.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential. Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts, it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration. The size of pores within implanted biomaterials has shown significant effects on macrophage polarization, which has been further confirmed as necessary for efficient vascular formation and remodeling. Here, we developed biodegradable, autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts' interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate. The synthetic vascular grafts showed similar mechanical properties to native blood vessels, encouraged macrophage populations with varying M2 to M1 phenotypic expression, and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model. This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

YiiP from Shewanella oneidensis is a prokaryotic Zn²⁺/H⁺ antiporter that serves as a model for the Cation Diffusion Facilitator (CDF) superfamily, members of which are generally responsible for homeostasis of transition metal ions. Previous studies of YiiP as well as related CDF transporters have established a homodimeric architecture and the presence of three distinct Zn²⁺ binding sites named A, B, and C. In this study, we use cryo-EM, microscale thermophoresis and molecular dynamics simulations to address the structural and functional roles of individual sites as well as the interplay between Zn²⁺ binding and protonation. Structural studies indicate that site C in the cytoplasmic domain is primarily responsible for stabilizing the dimer and that site B at the cytoplasmic membrane surface controls the structural transition from an inward facing conformation to an occluded conformation. Binding data show that intramembrane site A, which is directly responsible for transport, has a dramatic pH dependence consistent with coupling to the proton motive force. A comprehensive thermodynamic model encompassing Zn²⁺ binding and protonation states of individual residues indicates a transport stoichiometry of 1 Zn²⁺ to 2-3 H⁺ depending on the external pH. This stoichiometry would be favorable in a physiological context, allowing the cell to use the proton gradient as well as the membrane potential to drive the export of Zn²⁺.

The bacterial microbiota promotes the life cycle of the intestine-dwelling whipworm Trichuris by mediating hatching of parasite eggs ingested by the mammalian host. Despite the enormous disease burden associated with Trichuris colonization, the mechanisms underlying this transkingdom interaction have been obscure. Here, we used a multiscale microscopy approach to define the structural events associated with bacteria-mediated hatching of eggs for the murine model parasite Trichuris muris. Through the combination of scanning electron microscopy (SEM) and serial block face SEM (SBFSEM), we visualized the outer surface morphology of the shell and generated 3D structures of the egg and larva during the hatching process. These images revealed that exposure to hatching-inducing bacteria catalyzed asymmetric degradation of the polar plugs prior to exit by the larva. Unrelated bacteria induced similar loss of electron density and dissolution of the structural integrity of the plugs. Egg hatching was most efficient when high densities of bacteria were bound to the poles. Consistent with the ability of taxonomically distant bacteria to induce hatching, additional results suggest chitinase released from larva within the eggs degrade the plugs from the inside instead of enzymes produced by bacteria in the external environment. These findings define at ultrastructure resolution the evolutionary adaptation of a parasite for the microbe-rich environment of the mammalian gut.

The purpose of this study was to determine if the use of peripheral nerve blocks in the operative management of tibial plateau fractures is associated with improved outcomes when compared with the use of spinal and general anesthesia. Over a period of 16 years, 132 patients who underwent operative repair for a low-energy tibial plateau fracture and had at least 12 months of follow-up met the inclusion criteria and formed the basis of this study. Patients were grouped into cohorts based on the anesthetic method used during surgery: peripheral nerve block in combination with conscious sedation or general anesthesia (BA), general anesthesia alone (GA), or spinal anesthesia alone (SA). Outcomes were assessed at 3 months, 6 months, and 12 months. Length of stay was greatest in the GA cohort (P<.05), and more patients in the BA cohort were discharged to home (P<.05). Patients in the GA cohort had the highest pain scores at 3 months and 6 months (P<.05). Patients in both the SA and BA cohorts had better Short Musculoskeletal Function Assessment scores at 6 and 12 months when compared with the GA cohort (P<.05). Although knee range of motion did not differ among the three cohorts at 3 months, it did differ at 6 months and 12 months postoperatively, with those who had a preoperative nerve blockade (SA and BA) having the greatest knee range of motion (P<.05). Regional anesthesia was safe and was associated with lower pain scores in the early postoperative period and greater knee range of motion and functional outcome scores in the late postoperative period. [Orthopedics. 2023;46(6):358-364.].

OBJECTIVE:To report on demographics, injury patterns, management strategies and outcomes of patients who sustained fractures of the tibial plateau seen at a single center over a 16-year period. DESIGN/METHODS:Prospective collection of data.Patients/ Participants: 716 patients with 725 tibia plateau fractures, were treated by one of 5 surgeons. INTERVENTION/METHODS:Treatment of tibial plateau fractures. MAIN OUTCOME MEASUREMENTS/METHODS:Outcomes were obtained at standard timepoints. Complications were recorded. Patients were stratified into 3 groups: those treated in the first 5 years, those treated in the second 5 years and those treated in the most recent 6 years. RESULTS:608 fractures were followed for a mean 13.4 months (6-120) and 82% had a minimum 1-year follow up. Patients returned to self-reported baseline function at a consistent proportion during the 3 time periods. The average knee arc was 125 degrees (75 - 135 degrees) at latest follow up and did not differ over time. The overall complication rate following surgery was 12% and did not differ between time periods. Radiographs demonstrated excellent rates of healing and low rates of PTOA and improved articular reductions at healing (0.58 mm in group 3 compared to 0.94 mm in Group 1 and 1.12 mm in Group 2) (P<0.05). CONCLUSION/CONCLUSIONS:The majority of patients regained their baseline functional status following surgical intervention and healing. Over time the ability of surgeons to achieve a more anatomic joint reduction was seen, however this did not correlate with improved functional outcomes. LEVEL OF EVIDENCE/METHODS:Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.