Faculty Bibliography

We previously reported that topically applied calreticulin (CRT), a calcium-binding ER chaperone protein comprising N, P, and C domains, markedly enhances diabetic murine (db/db) and porcine cutaneous wound healing. Consistent with the potent wound healing effects, we further showed, in vitro, that exogenous CRT stimulated proliferation of keratinocytes and fibroblasts, induced concentration-dependent migration of these cells and monocytes and macrophages, and upregulated protein expression of collagen, fibronectin, and TGF-beta-3 in fibroblasts. Notably, all these broad-ranging effects purport novel non-ER functions for CRT that act from outside the cell inward. The current studies address: 1) whether the ER chaperone function of CRT is required for its extracellular functions, 2) the molecular structure(s) of CRT that function in its biological activities and 3) the in vitro effects of CRT on diabetic compared to normal mouse and human fibroblasts. Using CRT null mouse embryo fibroblasts (K42) compared to wild type (K41) in proliferation and migration assays (scratch plate and chamber), we show that exogenous CRT stimulates proliferation of null K42 cells to a similar extent as K41 cells (2-fold at 10 pg/ml). However, K42 cells require 100 times more CRT for a peak migratory response (1 vs 100 ng/ml), with a 20% decreased response. We also show that the C domain stimulates fibroblast proliferation to the same extent and peak response as the entire molecule. Finally, we show that fibroblasts isolated from db/db mouse skin and human fibroblasts cultured in high glucose, to simulate type II diabetes, respond to CRT by migration and proliferation albeit with 1/3 less robust response requiring 10-fold more CRT for peak responses compared to controls. The breath of novel non-ER functions of CRT, structure-function relationships, and effects on diabetic cells in vitro underscore this molecule as a potential potent agent for the topical treatment for healing diabetic wounds

Calcium phosphate-based bioactive ceramics in various physical and chemical formulations have been extensively utilized as biomaterials for bone regeneration/conduction. However, the determination of their in vivo temporal behavior from the short to long term in humans has been a challenge due to the lack of physical reference for morphologic and morphometric evaluation. The present study evaluated bone morphology and morphometry (bone-to-implant contact [BIC]) around plasma-sprayed hydroxyapatite (PSHA)-coated endosseous implants that were retrieved due to prosthetic reasons while successfully in function at the posterior region of the jaws from as early as 2 months to approximately 13 years after a 6-month healing period after placement. Bone morphology was evaluated by light microscopy, and BIC was determined using computer software. Irrespective of the time in vivo, lamellar bone was observed in close contact with the implant PSHA-coated surface and between plateaus. BIC ranged from approximately 35-95%, was highly directional, and Haversian-like osteonic morphology between plateaus was observed for most implants. The PSHA coating was present with little variation in thickness between the samples retrieved regardless of time in vivo.

OBJECTIVES: (1) Present a unique case of a thyroglossal duct cyst (TGDC) excised for recurrent infections with Trichinella spiralis in adjacent strap muscle; (2) review the literature regarding the diagnosis and treatment of subclinical trichinellosis of the head and neck. STUDY DESIGN: Case report and literature review. METHODS: Case report and literature review. RESULTS: We present the case of a male immigrant who suffered from recurrent midline neck infections due to aTGDC. The patient underwent an uneventful Sistrunk procedure. Histological examination of the surgical specimen revealed a chronically infected TGDC as well as remnants of skeletal muscle adjacent to the cyst containing nematode larvae, positively identified as Trichinella spiralis. The patient was subsequently evaluated by an infectious disease specialist and required no further treatment for his parasitic infection. DISCUSSION: The presence of nematode infections in developed countries is rare today given improved hygiene practices and control of meat quality. We present a unique case of incidentally noted Trichinella spiralis infection of the head and neck. To our knowledge, this is the first described case of trichinellosis of strap muscle adjacent to an excised TGDC and furthermore highlights the rarity of Trichinella spiralis infections of the head and neck. CONCLUSIONS: Trichinella spiralis may exist subclinically in a variety of human tissues including neck muscles

Purpose: Cutaneous radiation injury occurs during the treatment of cancer, or in rare environmental exposure. As the acute wound heals, fibrosis is induced and extracellular matrix (ECM) is deposited. The fibrotic pathway is mediated by the transforming growth factor-beta (TGF-beta) cascade, and is dependent on Smad3, a transcription factor for ECM. We characterized gene expression of this cascade after radiation injury and performed in vitro and in vivo gene silencing of Smad3 in an attempt to reverse the fibrotic pathway. Methods: Wild-type murine dermal fibroblasts were irradiated with 20Gy and harvested at serial time-points. RT-PCR was performed for known regulators and mediators of fibrosis. Smad3 was silenced by transfection with siRNA. For the in vivo experiment, dorsal skin of wild-type mice was irradiated with 45 Gy. Five weeks later, siRNA was applied to the fibrotic areas for one week. Skin was harvested and tissue analyzed by RT-PCR and Western blotting, as well as tissue tensiometry, which quantitatively measures rigidity. Results: Following irradiation, there was a steady increase in mRNA expression of Smad3, TGFbeta, and ECM genes collagen 1A1, metalloprotease2, and tissue inhibitor of metalloprotease-1, with peak expression at 12-24 hours. Inhibition of Smad3 with siRNA significantly decreased expression of Smad3, TGFbeta, and ECM genes. In the mouse model, topical treatment with siRNA again significantly decreased expression of these genes. Tensiometry demonstrated decreased stiffness in Smad3 siRNA treated skin, with a Young's modulus nearer to normalcompared to untreated and nonsense siRNA treated skin. Conclusion: Following initiation of the fibrotic pathway by radiation, Smad3 siRNA treatment both in vitro and in vivo effectively reversed gene expression. Furthermore, cutaneous Smad3 inhibition mitigated radiation-induced fibrotic stiffening. These findings suggest a therapeutic role for Smad3 silencing for cancer patients treated with radiation as well as those accidentally exposed to radiation

The positive results of the performance of zirconia for orthopedics devices have led the dental community to explore possible esthetical and mechanical outcomes using this material. However, questions regarding long-term results have opened strong and controversial discussions regarding the utilization of zirconia as a substitute for alloys for restorations and implants. This narrative review presents the current knowledge on zirconia utilized for dental restorations, oral implant components, and zirconia oral implants, and also addresses laboratory tests and developments, clinical performance, and possible future trends of this material for dental healthcare.

Summary form only given. This study aims to evaluate the potential of atmospheric pressure non-thermal plasma technology (NPT) to enhance the adhesive bond strength on normative dentin substrates. Two different microplasma jets were used in our experiments, a direct-current driven microhollow cathode discharge jet operated in air and a rf-driven jet operated in Ar. Other gas mixtures, e.g. He/O2 are also being explored.Initial experiments were carried out using fresh, non-carious third molars obtained under a protocol approved by the New York University College of Medicine Institutional Review Board. The occlusal enamel of each tooth was removed perpendicular to the long axis of the tooth to expose a flat dentin surface, which was subsequently polished. The specimens were randomly assigned to 3 groups for bonding and NPT applications. For the control group, three teeth were etched with phosphoric acid etched, the dentin bonding agent (DBA) was applied and the teeth were restored with a 4 mm thick resin composite. Another group of 3 teeth was treated with an Ar plasma and a third group was exposed to an air plasma. For the plasma-treated groups, the dentin substrates were etched for 15 s, rinsed for 10s and treated by the plasma for 20 s followed by DBA application and resin composite placement. All specimens were stored in water for 24 h prior to a microtensile bonding test. Preliminary data indicate that the bond strength values were not significantly affected by the Ar or air plasma treatment. We observed that teeth treated with the Ar plasma exhibited an enhanced premature failure rate (-50%) during the cutting or specimen mounting phases. This was not observed for the control or for the air plasma treated groups. Extensive surface characterization studies using various microscopy techniques, XPS, and micro-Raman are underway to assess the effect of the plasma on the surface. Optical emission spectroscopy is used to monitor the presence of reactive spe- - cies (eg. OH, O) in the plasma for various operating conditions and feed gases or gas mixtures. The results of these studies will be presented and discussed in detail at the Conference