Searched for: school:SOM
Department/Unit:Plastic Surgery
Effect of bioceramic inclusions on gel-cast aliphatic polymer membranes for bone tissue engineering applications: An in vitro study
Nayak, Vasudev Vivekanand; Bergamo, Edmara T P; Sanjairaj, Vijayavenkataraman; Behera, Rakesh Kumar; Gupta, Nikhil; Coelho, Paulo G; Witek, Lukasz
BACKGROUND/UNASSIGNED:Polylactic acid (PLA) has been extensively used in tissue engineering. However, poor mechanical properties and low cell affinity have limited its pertinence in load bearing bone tissue regeneration (BTR) devices. OBJECTIVE/UNASSIGNED:Augmenting PLA with β-Tricalcium Phosphate (β-TCP), a calcium phosphate-based ceramic, could potentially improve its mechanical properties and enhance its osteogenic potential. METHODS/UNASSIGNED:Gels of PLA and β-TCP were prepared of different % w/w ratios through polymer dissolution in acetone, after which polymer-ceramic membranes were synthesized using the gel casting workflow and subjected to characterization. RESULTS/UNASSIGNED:Gel-cast polymer-ceramic constructs were associated with significantly higher osteogenic capacity and calcium deposition in differentiated osteoblasts compared to pure polymer counterparts. Immunocytochemistry revealed cell spreading over the gel-cast membrane surfaces, characterized by trapezoidal morphology, distinct rounded nuclei, and well-aligned actin filaments. However, groups with higher ceramic loading expressed significantly higher levels of osteogenic markers relative to pure PLA membranes. Rule of mixtures and finite element models indicated an increase in theoretical mechanical strength with an increase in β-TCP concentration. CONCLUSION/UNASSIGNED:This study potentiates the use of PLA/β-TCP composites in load bearing BTR applications and the ability to be used as customized patient-specific shape memory membranes in guided bone regeneration.
PMID: 39331087
ISSN: 1878-3619
CID: 5739342
Dermal β-Catenin Is Required for Hedgehog-Driven Hair Follicle Neogenesis
Lim, Chae Ho; Kaminaka, Annette; Lee, Soung-Hoon; Moore, Simone; Cronstein, Bruce N; Rabbani, Piul S; Ito, Mayumi
Hair follicle neogenesis (HFN) occurs following large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Wound healing typically results in fibrosis in mice and humans. We previously showed small skin excisions in mice result in scarring devoid of HFN, displaying features of non-regenerative healing, and Hedgehog (Hh) activation in the dermis of such wounds can induce HFN. In this study, we sought to verify the role of dermal Wnt/β-catenin signaling in HFN, as this pathway is essential for HF development, but is also paradoxically well-characterized in fibrosis of adult wounds. By deletion of β-catenin in large wound myofibroblasts, we show Wnt/β-catenin signaling is required for endogenous mechanisms of HFN. Through utilizing a combined mouse model that simultaneously induces deletion of β-catenin and constitutive activation of Smoothened (Smo) in myofibroblasts, we also found β-catenin is required for Hh-driven DP formation. Transcriptome analysis confirms Wnt/β-catenin and Hh pathways are activated in dermal papilla (DP) cells. Our results indicate that Wnt-active fibrotic status may also create a permissive state for the regenerative function of Hh, suggesting that activation of both Wnt and Hh pathways in skin wound fibroblasts must be ensured in future strategies to promote HFN.
PMID: 38810955
ISSN: 1523-1747
CID: 5663682
Programmed Cell Death Protein 1 Contributes to Oral Cancer Pain via Regulating Tumor Necrosis Factor Alpha in the Spinal Trigeminal Nucleus Caudalis
Mao, Runyi; Liu, Sufang; Dolan, John C; Schmidt, Brian L; Tao, Feng
BACKGROUND:Oral cancer causes intense pain at the primary site, and such pain can impair oral functions. However, the underlying mechanisms for oral cancer pain are still not fully understood. In the present study, it is investigated whether programmed cell death protein 1 (PD-1) is involved in the development of oral cancer pain. METHODS:RMP1-14, a specific anti-PD-1 antibody, was injected into spinal trigeminal nucleus caudalis (Sp5C) and measured pain behaviors using von Frey filaments and dolognawmeter. Western blotting and immunofluorescence staining were performed to analyze the expression of PD-1 and tumor necrosis factor alpha (TNFα) in the Sp5C. RESULTS:It was observed that the PD-1 antibody significantly inhibited mechanical hypersensitivity and functional allodynia in our oral cancer pain mouse model. Moreover, we found that TNFα was highly upregulated in the Sp5C following the induction of oral cancer pain and that intra-Sp5C injection of the PD-1 antibody diminished the upregulation of TNFα. It was found that genetic deletion of TNFα or its receptor antagonism synergized the analgesic effect of PD-1 antibody on oral cancer pain. CONCLUSION/CONCLUSIONS:Our results suggest that PD-1 in the Sp5C contributes to oral cancer pain by altering TNFα signaling in the trigeminal nociceptive system, and PD-1 could be targeted to develop a novel approach for oral cancer pain management.
PMID: 39660489
ISSN: 1875-6190
CID: 5766032
Nipple Areolar Complex (NAC) Neurotization After Nipple-Sparing Mastectomy (NSM) in Implant-Based Breast Reconstruction: A Systematic Review of the Literature
Sorenson, Thomas J; Boyd, Carter J; Park, Jenn J; Hemal, Kshipra; Amro, Chris; Vernice, Nicholas; Lakatta, Alexis; Cohen, Oriana; Karp, Nolan; Choi, Mihye
BACKGROUND/UNASSIGNED:Nipple-sparing mastectomy (NSM) with implant-based breast reconstruction (IBBR) preserves the nipple-areolar complex (NAC) with superior aesthetic results but results in loss of nipple sensation. Nipple neurotization has emerged as a technique to restore the sensory function, yet outcomes remain variable across studies. This systematic review synthesizes the available evidence on nipple neurotization in IBBR, focusing on sensory recovery, patient satisfaction, and surgical techniques. METHODS/UNASSIGNED:A systematic review was conducted following PRISMA guidelines. PubMed, Ovid EMBASE, and Cochrane Library were searched through April 1, 2025, for studies evaluating nipple neurotization in IBBR. Eligible studies included randomized controlled trials, cohort studies, and case series reporting surgical technique, sensory, and/or patient satisfaction outcomes. Data extraction included study characteristics, surgical techniques, sensory outcomes, and patient-reported satisfaction. Risk of bias was assessed using standardized tools. RESULTS/UNASSIGNED:Six studies met inclusion criteria, comprising 212 patients and 257 neurotized breasts. Sensory recovery was assessed using monofilament testing and patient-reported outcomes. Studies demonstrated overall improvement of NAC sensory outcomes and high patient satisfaction after neurotization. However, variability in neurotization methods, follow-up duration, and specific measured sensory outcomes limited direct comparisons. CONCLUSION/UNASSIGNED:Nipple neurotization in IBBR shows promise in enhancing sensory recovery and patient satisfaction after NSM, but heterogeneity in surgical techniques and outcome measures, as well as poor study designs, limits definitive conclusions. Standardized protocols and randomized studies with long-term patient follow-up are needed to establish best practices and optimize neurotization outcomes.
PMCID:12517998
PMID: 41089735
ISSN: 1524-4741
CID: 5954752
BIOMIMETICS
Munkwitz, Sara E.; Ting, Albert; Shah, Hana; Iglesias, Nicholas J.; Nayak, Vasudev Vivekanand; Castellano, Arthur; Witek, Lukasz; Coelho, Paulo G.
ISI:001603801900001
CID: 5966052
Life course perspective for improving oral health: strategies and interventions to integrate oral health care and primary health care in community health centers
Northridge, Mary E; Lieberman, Martin
In the United States, disparities in access to quality oral health care exist at every stage across the life course. The net result is a greater likelihood of poor oral health at every age for people who live in underserved and rural communities than for people who live in communities with better access to quality oral health care. Both universal and targeted interventions at multiple levels of influence across the life course and intergenerationally are needed to eliminate disparities in access to oral health care and end the disgrace of poor oral health as the US national symbol of social inequality. While community health centers hold promise for delivering patient-centered, value-based care, they experience challenges related to the oral health literacy of patients and organizations and to the building of sufficient capacity to meet the high demand for oral health care services. To address the training needs of the US dentistry workforce, the long-term goal of the New York University Langone Dental Medicine Postdoctoral Residency Programs is to improve oral health care access and delivery across the life course for people of all ages and intergenerationally. The short-term goal is to recruit and train dentists to lead patient-centered models of integrated care delivery at community health centers in underserved and rural communities of 30 US states, Puerto Rico, and the US Virgin Islands. This paper presents the capstone findings of a 5-year postdoctoral dental residency training project built upon a foundation of shared decision-making and motivational interviewing training for dental faculty and residents. Improving patient experience and patient-reported outcomes are critical in transforming dentistry from a fee-for-service to a value-based health care model. Scaling up promising interventions and addressing time and resource constraints in community health centers require the broad commitment of communities, organizations, patients and their families in demanding and realizing the US societal goal of oral health for all.
PMCID:12511061
PMID: 41080811
ISSN: 2673-4842
CID: 5954482
Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia
Teng, Shavonne L.; Latorre, Rocco; Bhansali, Divya; Lewis, Parker K.; Pollard, Rachel E.; Peach, Chloe J.; Sokrat, Badr; Arasu, Gokul Sriman Thanigai; Chiu, Tracy; Duran, Paz; Jimenez, Nestor N.; Mocherniak, Abby; Bogyo, Matthew; Gaspari, Michael M.; Vanner, Stephhen J.; Pinkerton, Vanne Nathalie M.; Leong, Kam W.; Schmidt, Brian L.; Jenson, Dane D. J.; Bunnett, Nigel W.
ISI:001600879100001
ISSN: 0027-8424
CID: 5966022
Gracilis Free Flap Technique for Elbow Flexion Reconstruction
Sanchez-Navarro, Gerardo E; Perez-Otero, Sofia; Lowe, Dylan T; Hacquebord, Jacques H; Agrawal, Nikhil
BACKGROUND/UNASSIGNED:. In this video article, we present the exploration of a complex BPI in which the creation of a gracilis free flap is executed for elbow flexion reconstruction. We provide a comprehensive guide from markings, flap elevation, microsurgical technique, and inset, with educational operative pearls at every step. DESCRIPTION/UNASSIGNED:The procedure involves harvesting the gracilis muscle as a free functioning muscle transfer. The gracilis, which will become a type-II muscle flap, is carefully dissected with its pedicle and nerve preserved. The muscle is then transferred to the upper extremity, where its proximal origin is anchored to the clavicle and its distal tendon is inserted into the biceps tendon with use of a Pulvertaft weave. Vascular anastomoses are performed utilizing branches of the thoracoacromial trunk and venous couplers under a microscope. The muscle is innervated with the spinal accessory nerve and tensioned to ensure optimal elbow flexion. ALTERNATIVES/UNASSIGNED:Surgical alternatives include nerve transfers (e.g., Oberlin transfer), tendon transfers, or other free muscle transfers (e.g., latissimus dorsi transfer). Nonsurgical alternatives include orthotic devices to compensate for elbow flexion loss, and physical therapy to maximize existing function. RATIONALE/UNASSIGNED:. Unlike orthotic devices, this technique provides active elbow flexion, critical for functional independence. The long tendon and reliable vascular pedicle make the gracilis ideal for this purpose. EXPECTED OUTCOMES/UNASSIGNED:. These findings suggest that free gracilis muscle transfer provides reliable functional improvements, enabling meaningful elbow flexion restoration and enhancing quality of life. IMPORTANT TIPS/UNASSIGNED:Utilize Doppler ultrasound to confirm the location of a skin perforator over the gracilis to aid in postoperative monitoring.Preoperative markings are key. Mark the orientation of the gracilis muscle belly and pedicle preoperatively for efficient harvesting.The gracilis inserts distal to the knee, so extending the knee can help distinguish it from the adductor longus.Preserve all fascia over the gracilis muscle to optimize muscle gliding.Ensure proper resting tension during gracilis insertion to prevent over- or under-tightening, optimize function, and avoid complications like hyperextension or limited flexion.Position the elbow at 90° of flexion and the forearm in supination when tensioning.Make accommodation for any vessel size mismatch between the gracilis pedicle and recipient vessels to minimize complications.Confirm intraoperative vessel patency with use of Doppler flow checks after completing the anastomoses.Confirm nerve viability intraoperatively with use of nerve stimulation, ensuring a strong muscle contraction response.Secure the nerve repair without tension and with the appropriate coaptation in order to maximize reinnervation success.Utilize drains to avoid fluid collections that can create pressure on the pedicle.Place the gracilis tendon insertion precisely with use of the Pulvertaft weave technique, ensuring secure fixation and proper alignment with the biceps tendon. ACRONYMS AND ABBREVIATIONS/UNASSIGNED:BPI = brachial plexus injuryDASH = Disabilities of the Arm, Shoulder and HandDVT = deep vein thrombosisEMG = electromyographyFFMT = free functioning muscle transferFGMT = free gracilis muscle transferICN = intercostal nerve transferM3/M4 = muscle strength grade 3 or 4MCA = medial circumflex arteryMCN = musculocutaneous nerveNCS = nerve conduction studyPPX = prophylaxisSAN = spinal accessory nerveSF-36 = Short Form-36.
PMCID:12269806
PMID: 40678176
ISSN: 2160-2204
CID: 5897532
TRPV4 activation in Schwann cells mediates mechanically induced pain of oral cancer
Mulpuri, Yatendra; Tu, Nguyen H; Inoue, Kenji; Harden, Grace; Nicholson, Samuel J; Seenauth, Anisa; Huang, Yan; Escobar, Keylin G; Moayedi, Yalda; Bunnett, Nigel W; Albertson, Donna G; Schmidt, Brian L
INTRODUCTION/UNASSIGNED:Patients with oral cancer often experience intense functional pain due to mechanical stimulation at the cancer site. The role of mechanosensitive ion channels in oral cancer pain, such as TRPV4, is not fully understood. OBJECTIVES/UNASSIGNED:Our objective was to investigate the role of Schwann cell TRPV4 in oral cancer pain. METHODS/UNASSIGNED:imaging, and patch-clamp electrophysiology. The effect of TRPV4 activation on Schwann cell responses to mechanical stimulation was evaluated using a piezo stimulator. Conditioned media (CM) from TRPV4-activated Schwann cells were injected into the mouse paw to evaluate the contribution of TRPV4 in Schwann cells to mechanical hypersensitivity. RESULTS/UNASSIGNED:responses and whole-cell membrane currents in human Schwann cells. Mechanoactivated currents in human Schwann cells were inhibited by the TRPV4 antagonist HC-067047. Schwann cell CM induced mechanical hypersensitivity in mice, which was blocked by pre-treatment with HC-067047. CONCLUSION/UNASSIGNED:TRPV4 activation plays a role in mediating mechanically induced pain of oral cancer.
PMCID:11937083
PMID: 40144515
ISSN: 2673-561x
CID: 5814392
An evaluation of novel AMP2-coated electrospun composite scaffolds for intraoral bone regeneration: a proof-of-concept in vivo study
Slavin, Blaire V; Wu, Shangtao; Sturm, Savanah R; Hwang, Kevin K; Almada, Ricky; Mirsky, Nicholas A; Nayak, Vasudev Vivekanand; Witek, Lukasz; Coelho, Paulo G
BACKGROUND/UNASSIGNED:performance of a novel electrospun composite scaffold coated in a recombinant variant of human bone morphogenetic protein-2 (OsteoAdapt) relative to a porcine-derived xenograft. Further, it sought to determine if OsteoAdapt would remain within the defect without a membrane in place, as this is not feasible with the particulate xenograft currently used in clinical practice. METHODS/UNASSIGNED:, bone regeneration was assessed through qualitative volumetric reconstruction, qualitative and quantitative histological analyses. RESULTS/UNASSIGNED:= 0.982, respectively). However, qualitative analysis of the histological micrographs demonstrated advanced bone healing characterized by an abundance of nucleation sites for regeneration to occur in defects treated with OA relative to the CTRL. Bone overgrowth beyond the limits of defect borders was observed in groups treated OA/ZM and OA/P/ZM. In contrast to the treatment groups, minimal woven bone was visualized in the CTRL group. CONCLUSION/UNASSIGNED:. This suggests that the novel combination of AMP-2 and a bioceramic/synthetic polymer-based electrospun scaffold is a suitable candidate for GBR procedures, without a barrier membrane to secure its place within a defect.
PMCID:12043485
PMID: 40313641
ISSN: 2296-4185
CID: 5834402