Faculty Bibliography

BACKGROUND/UNASSIGNED:A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. METHODS/UNASSIGNED:Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. RESULTS/UNASSIGNED:significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. CONCLUSIONS/UNASSIGNED:The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

OBJECTIVES/OBJECTIVE:To evaluate the effects of dentin biomodification agents (Proanthocyanidin (PAC), Cardol (CD) and Cardol-methacrylate (CDMA) on dentin hydrophilicity by contact angle measurement, viability of dental pulp stem cells (DPSCs) and nanomechanical properties of the hybrid layer (HL). METHODS:CDMA monomer was synthesized from cardol through methacrylic acid esterification. Human extracted third molars were used for all experiments. For nanomechanical tests, specimens were divided in four groups according to the primer solutions (CD, CDMA, PAC and control) were applied before adhesive and composite coating. Nanomechanical properties of the HL were analyzed by nanoindentation test using a Berkovich probe in a nanoindenter. Wettability test was performed on dentin surfaces after 1 min biomodification and measured by contact angle analysis. Cytotoxicity was assessed by a MTT assay with DPSCs after 48 and 72 h. Data were analyzed with Student's t test or Two-way ANOVA and Tukey HSD test (p < 0.05). RESULTS:CD and CDMA solutions achieved greater hydrophobicity and increased the water-surface contact angles when compared to PAC and control groups (p < 0.05). PAC group showed a greater reduction of elastic modulus in nanoindentation experiments when compared to CD and CDMA groups (p < 0.05) after 4 months of aging. CD inhibited cell proliferation compared to all further materials (p < 0.05), whilst CDMA and PAC indicated no cell cytotoxicity to human DPSCs. SIGNIFICANCE/CONCLUSIONS:Cardol-methacrylate provided significantly higher hydrophobicity to dentin and demonstrated remarkable potential as collagen crosslinking, attaining the lowest decrease of HL's mechanical properties. Furthermore, such monomer did not affect pulp cytotoxicity, thereby highlighting promising feasibility for clinical applications.

This study evaluated the rheological properties of various hyaluronic acid (HA) gels after passing through different-sized cannulas (22-G and 25-G). Five commercial brands of highly crosslinked HA fillers were analyzed: (A) Rennova® Ultra Deep, (B) Restylane® Lyft, (C) Hialurox® - Ultra Lift, (D) Belotero® Volume, and (E) E.P.T.Q S500. Rheological characterization was conducted using an automated controlled stress rheometer. The rheological properties of the fillers were assessed both before and after passing through the cannulas. Each filler brand and cannula size was tested three times by a researcher who was blinded to the commercial brands. For data analysis, frequencies of 0.1, 0.5, and 2 Hz were employed. The rheological properties (storage modulus [G'] and loss modulus [G"]) of the high-crosslink HA fillers did not change after being passed through cannulas of different sizes (22-G and 25-G) (p > 0.109) compared to baseline measurements (no cannula). Furthermore, all fillers displayed desirable solid-like, volumizing behavior at low frequencies and strain amplitudes (<10 %). Under physiologically relevant conditions for skin and facial applications, the cannula size did not alter the rheological properties of high crosslink HA fillers.

Bone tissue regeneration is a rapidly evolving field aimed at the development of biocompatible materials and devices, such as scaffolds, to treat diseased and damaged osseous tissue. Functional scaffolds maintain structural integrity and provide mechanical support at the defect site during the healing process, while simultaneously enabling or improving regeneration through amplified cellular cues between the scaffold and native tissues. Ample research on functionalization has been conducted to improve scaffold-host tissue interaction, including fabrication techniques, biomaterial selection, scaffold surface modifications, integration of bioactive molecular additives, and post-processing modifications. Each of these methods plays a crucial role in enabling scaffolds to not only support but actively participate in the healing and regeneration process in bone and joint surgery. This review provides a state-of-the-art, comprehensive overview of the functionalization of scaffold-based strategies used in tissue engineering, specifically for bone regeneration. Critical issues and obstacles are highlighted, applications and advances are described, and future directions are identified.

This review focuses on advancements in polymer science as it relates to three-dimensional (3D) and four-dimensional (4D) printing technologies, with a specific emphasis on applications in the biomedical field. While acknowledging the breadth of 3D and 4D printing applications, this paper concentrates on the use of polymers in creating biomedical devices and the challenges associated with their implementation. It explores integrative modeling and experimental insights driving innovations in these fields, focusing on sustainable manufacturing with biodegradable polymers, a comparative analysis of 3D and 4D printing techniques, and applications in biomedical devices. Additionally, the review examines the materials used in both 3D and 4D printing, offering a detailed comparison of their properties and applications. By highlighting the transformative potential of these technologies in various industrial and medical applications, the paper underscores the importance of continued research and development. The scope of this review also includes an overview of future research directions to address current challenges, enhance material capabilities, and explore practical applications.

Osseodensification enhances the stability of endosteal implants. However, pre-clinical studies utilizing osseodensification instrumentation do not account for the limited presence of trabeculae seen clinically. This study aimed to evaluate the effect of osseodensification instrumentation on osteotomy healing in scenarios with and without the presence of trabecular bone. A ~10 cm incision was made over the hip of twelve sheep. Trabecular bone was surgically removed from twelve sites (one site/animal; negative control (Neg. Ctrl)) and left intact at twelve sites (one site/animal; experimental group (Exp.)). All osteotomies were created using the osseodensification drilling protocol. Each osteotomy received an endosteal implant and was evaluated after 3 or 12 weeks of healing (n = 6 animals/time). Histology revealed increased woven and lamellar bone surrounding the implants in the Exp. group relative to the Neg. Ctrl group. The Exp. group demonstrated the presence of bone fragments, which acted as nucleating sites, thereby enhancing the bone formation and remodeling processes. Bone-to-implant contact (%BIC) and bone area fractional occupancy (%BAFO) were significantly higher in the Exp. group relative to the Neg. Ctrl group both at 3 weeks (p = 0.009 and p = 0.043) and 12 weeks (p = 0.010 and p = 0.008). Osseodensification instrumentation in the presence of trabecular bone significantly improved osseointegration. However, no negative influences such as necrosis, inflammation, microfractures, or dehiscence were observed in the absence/limited presence of trabeculae.

BACKGROUND/UNASSIGNED:The purpose of this study is to determine the diagnostic capability of ultrasonography (US) in patients with suspected brachial plexus injury (BPI) to the terminal nerves by comparing physical examination (PE) findings with US, electromyography (EMG), and magnetic resonance imaging (MRI) reports. METHODS/UNASSIGNED:All patients at a single institution who underwent US for peripheral nerve injury of the brachial plexus and terminal nerves resulting in sensory-motor deficits from October 1, 2017 to October 31, 2023 were identified. A retrospective chart review was performed. Each PE, US, EMG, and MRI reports were given an overall rating: "normal" or "abnormal." Terminal nerves (musculocutaneous, axillary, radial, ulnar, medial) were individually assessed as "normal" or "abnormal." The interobserver agreement between reports was calculated using Cohen kappa. Specificity and sensitivity analyses were performed to determine diagnostic accuracy and were reported with 95% confidence intervals (CI). RESULTS/UNASSIGNED:A total of 120 patients were included. Most injuries were traumatic in nature (78.8%) and were low-energy (53.8%). When each imaging modality was compared with the PE findings, EMG had the highest interobserver agreement (Cohen kappa = 0.18), followed by US (Cohen kappa = 0.10), and last MRI (Cohen kappa = 0.07). The US had the highest sensitivity (0.92, CI = 0.85, 0.96) among the 3 imaging modalities (Table 2). On US, the ulnar nerve was most commonly abnormal (n = 84, 70.0%). DISCUSSION/UNASSIGNED:Ultrasonography serves as a useful adjunct in the workup of patients with suspected peripheral BPI and is reliable in localizing the pathology of injured terminal nerves in the brachial plexus.

Exosomes are being increasingly explored in biomedical research for wound healing applications. Exosomes can improve blood circulation and endocrine signaling, resulting in enhanced cell regeneration. However, exosome treatments suffer from low retention and bioavailability of exosomes at the wound site. Hydrogels are a popular tool for drug delivery due to their ability to encapsulate drugs in their network and allow for targeted release. Recently, hydrogels have proven to be an effective method to provide increased rates of wound healing when combined with exosomes that can be applied noninvasively. We have designed a series of single-domain protein-based hydrogels capable of physical cross-linking and upper critical solution temperature (UCST) behavior. Hydrogel variant Q5, previously designed with improved UCST behavior and a significantly enhanced gelation rate, is selected as a candidate for encapsulation release of exosomes dubbed Q5Exo. Q5Exo exhibits low critical gelation times and significant decreases in wound healing times in a diabetic mouse wound model showing promise as an exosome-based drug delivery tool and for future hybrid, noninvasive protein-exosome design.

This case series describes the successful use of indocyanine green dye and near infrared fluorescence imaging in primary peripheral nerve repair.