Faculty Bibliography

Nanostructure modification of dental implants has long been sought as a means to improve osseointegration through enhanced biomimicry of host structures. Several methods have been proposed and demonstrated for creating nanotopographic features; here we describe a nanoscale hydroxyapatite (HA)-coated implant surface and hypothesize that it will hasten osseointegration and improve its quality relative to that of non-coated implants. Twenty threaded titanium alloy implants, half prepared with a stable HA nanoparticle surface and half grit-blasted, acid-etched, and heat-treated (HT), were inserted into rabbit femurs. Pre-operatively, the implants were morphologically and topographically characterized. After 3 weeks of healing, the samples were retrieved for histomorphometry. The nanomechanical properties of the surrounding bone were evaluated by nanoindentation. While both implants revealed similar bone-to-implant contact, the nanoindentation demonstrated that the tissue quality was significantly enhanced around the HA-coated implants, validating the postulated hypothesis.

BACKGROUND: : The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24) mouse could serve as a model of senescent wound healing. METHODS: : Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24 mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. RESULTS: : Zmpste24 mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24 wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. CONCLUSIONS: : The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24 progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

BACKGROUND: Pathologic analysis of deep tissue obtained during debridement of venous ulcers is often unnoticed in its importance. We previously reported pathologic findings on 139 patients with venous ulcers. The objective of this study was to correlate the pathologic findings in venous ulcers with wound healing to establish a negative margin for debridement. STUDY DESIGN: Consecutive patients with a lower extremity venous ulcer present for at least 4 weeks, presenting to a single wound healing center, were included. Wounds underwent aggressive surgical debridement beyond the subcutaneous level until judged to have a viable base. Specimens were scored based on cellularity, vascularity, collagen composition, inflammation, and dense fibrosis, with a highest possible score of 13. Healing was the primary outcome for analysis. RESULTS: Of the 26 patients who met inclusion criteria, only 50% of them (13 patients) with a total of 18 venous ulcers underwent surgical debridement available for pathologic analysis. Mean ulcer area was 34.7 cm(2) at initial presentation, and 89% of patients had a continuous positive healing curve as measured by decreasing wound area (from 34.7 cm(2) to 14.3 cm(2)). However, specimens with dense fibrosis, decreased cellularity, mature collagen, and pathology score less than 10 were predominantly nonhealing ulcers. CONCLUSIONS: Presence of dense fibrosis and high levels of mature collagen in deep tissue specimens are significant correlative factors in nonhealing of venous ulcers. We recommend deep debridement on all venous ulcers that are refractory to healing until the level of absence of dense fibrosis and mature collagen is reached to promote venous ulcer healing.

Encased in lacunae, osteocytes receive nutrition and biomechanical signals through the lacunocanalicular system. We have developed a novel flow-perfusion bioreactor designed to support lacunocanalicular fluid flow. We hypothesize that ex vivo fluid flow can maintain endochondral bone viability and, ultimately, serve as a novel model to study bone biology in vitro. Sprague-Dawley rat femurs were harvested, stripped of soft tissue, loaded into a custom-designed bioreactor and perfused with osteogenic culture medium. After 14 days of flow-perfusion or static culture, the bones were harvested, fixed, decalcified, embedded, sectioned and stained with haematoxylin and eosin. Fresh long bone samples were similarly processed for comparison. Osteocyte viability and function were also evaluated, using thiazolyl blue tetrazolium bromide (MTT), fluorospectrophotometric DNA quantification, alkaline phosphatase (ALP) colorimetric assay and fluorochrome labelling of mineralizing surfaces. All samples remained free of infection throughout the study period. After 14 days of flow perfusion, histological analysis showed normal-appearing bony architecture, with 72% of lacunae being osteocyte-filled compared with 93% in freshly harvested samples and only 36% in static samples. MTT staining and assay confirmed osteocyte viability in the flow-perfusion samples as well as in fresh samples. DNA quantification demonstrated DNA to be preserved in flow-perfused samples when compared with freshly harvested samples. ALP activity in flow-perfusion explants was upregulated compared with fresh and static samples. Fluorochrome-labelled mineralizing surfaces were seen throughout the explanted flow-perfused samples. This is the first demonstration that flow perfusion provides adequate chemotransportation to explanted murine endochondal bones

INTRODUCTION: Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients. METHODS: A review of all patients admitted to the ICU with a diagnosis of LGIB over a 13-year period was performed. A total of 60 patients received subcutaneous heparin along with mechanical prophylaxis, whereas 59 patients had intermittent pneumatic compression devices alone. RESULTS: There was no difference in morbidity or mortality between the groups who received heparin and the nonheparin cohort. Neither of the groups developed a DVT or PE during the study period. Patients who received heparin had a median ICU LOS of 3 days, when compared with 2 days for patients who did not receive heparin (P < .0118). There was a significant association between units of blood received during the first 24 hours in the ICU and heparin usage (P < .0229). Those administered heparin received more units (median 3) than those who did not receive heparin (median 2). CONCLUSIONS: Administration of subcutaneous heparin increases the transfusion requirements and LOS in ICU patients with LGIB. After 24 hours, however, the blood transfusion requirements are equivalent. DVT prophylaxis in patients with a diagnosis of LGIB should be initiated after 24 hours of ICU admission.

BACKGROUND: Reconstruction of the maxilla with the fibula free flap is a popular and well-described technique. The ideal intraoral lining would be mucosa, which is moist, thin, and non-hair-bearing. Prelamination of the fibula with buccal mucosa replaces like tissue with like tissue, obviates the need for a skin paddle, and facilitates placement of osseointegrated implants in a single stage. For central maxillary defects, the authors have shifted from using an osteocutaneous to a prelaminated free fibula flap. In this article, the authors report their experience using the prelaminated osteomucosal fibula for maxillary reconstruction. METHODS: From 2003 to 2011, 24 patients underwent reconstruction of a central maxillary defect using a free fibula flap. The first 10 patients had osteoseptocutaneous flaps, and the other 14 patients had prelaminated flaps. Data collected included patient age, cause of defect, type and number of operations, complications at both the donor and recipient sites, and placement of osseointegrated implants. RESULTS: The majority of patients in the series (n = 21) had central maxillary defects caused by loss of the premaxilla during early repair of bilateral cleft lip-cleft palate. There was one flap failure in the nonprelaminated flap group and one in the prelaminated group. Repeated debulking to thin the skin paddle was required in all of the patients with osteocutaneous flaps. CONCLUSIONS: Prelamination delivers like tissue to the recipient site, obviates the need for debulking, and may reduce donor-site wound problems. To the authors' knowledge, this is the largest series of prelaminated fibulas for maxillary reconstruction in the literature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Human papillomavirus (HPV) is an emerging risk factor for oropharyngeal cancer, especially among younger patients, and must be thoughtfully addressed by the dental community. The professional ethical decision-making model first advanced by Ozar and Sokol for use by dentists at chairside (define the dilemma, assess the facts, identify and rank the alternatives, and choose a course of action) was modified to delineate clearly inputs, considerations, and feedback loops based on what is professionally and ethically at stake in advising patients. As the link between HPV and oropharyngeal cancer is established through scientific studies, the role of the dentist in primary and secondary prevention will be crucial. In the absence of definitive evidence, the professional ethical decision-making framework presented here allows dentists to systematically work through available alternatives. Ultimately, the role of the dentist is to use discretion in choosing a professional and ethical course of action for each patient.

OBJECTIVE:We report on the case of an 11-year-old girl with atypical neurothekeoma of the left lateral alar rim that was excised and ultimately closed primarily after an unsuccessful attempt at reconstruction with a full-thickness auricular composite graft. METHODS:In this case report, we present a description of the case and a review of the literature. RESULTS:The patient underwent successful excision of neurothekeoma and subsequent auricular cartilage graft reconstruction. Reconstruction failed to adequately heal at several months postoperatively and the defect was closed primarily. CONCLUSIONS:Rapidly growing nodules of the nose can have a broad differential and requires pathological diagnosis via early biopsy. This is important because the surgical approach varies depending on the lesion and its potential for metastasis and local growth.