Faculty Bibliography

BACKGROUND:Although platelet-rich plasma (PRP) is used clinically to augment tendon healing, bone morphogenetic protein-13 (BMP13) may provide a better therapeutic avenue to improve early tendon healing and repair. HYPOTHESIS/OBJECTIVE:Exogenous expression of BMP13 in tenocytes will up-regulate genes involved in tendon healing. Direct delivery of adenovirus-mediated BMP13 (AdBMP13) into the injured rat supraspinatus tendon will increase biomechanical properties. STUDY DESIGN/METHODS:Controlled laboratory study. METHODS:Exogenous expression of BMP13 and the major growth factors in PRP (transforming growth factor-β1 [TGF-β1], vascular endothelial growth factor-A [VEGF-A], and platelet-derived growth factor-BB [PDGF-BB]) was accomplished by using recombinant adenoviral vectors. The expression of tendon- and matrix-associated genes in growth factor-treated tenocytes was analyzed by use of semiquantitative reverse-transcription polymerase chain reaction. A total of 32 rats with supraspinatus defect were divided into 4 groups and injected with adenovirus-containing green fluorescent protein (AdGFP; negative control), PRP, AdBMP13, or PRP+AdBMP13. All rats were sacrificed at 2 weeks after surgery, and tendons were harvested for biomechanical testing and histologic analysis. RESULTS:BMP13 up-regulated type III collagen expression compared with AdGFP control and PRP growth factors (P < .01). BMP13 and PRP growth factors each up-regulated fibronectin expression (P < .01). There was an increase in stress to failure in each of the 3 treatment groups (P < .05 for PRP; P < .01 for AdBMP13 or PRP+AdBMP13) compared with AdGFP control. AdBMP13 demonstrated higher stress to failure than did the PRPs (P < .01). The addition of PRP did not increase the BMP13-enhanced stress to failure or stiffness. The biomechanical results were further supported by histologic analysis of the retrieved samples. CONCLUSION/CONCLUSIONS:Exogenous expression of BMP13 enhances tendon healing more effectively than PRP as assessed by tendon- and matrix-associated gene expression, biomechanical testing, and histologic analysis. CLINICAL RELEVANCE/CONCLUSIONS:While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.

BACKGROUND: Over the past decade, facial vascularized composite allotransplantation has earned its place at the top of the reconstructive ladder. However, as in free tissue transfer, postoperative revisions are necessary to achieve optimal functional and aesthetic results. Although revising a facial vascularized composite allotransplantation may potentially risk the integrity of the graft, the authors believe that the advantages of appropriately chosen revisions may provide great benefit. METHODS: Following the most extensive face transplant performed to date, revisions were performed in two surgical procedures. The first included a Le Fort III osteotomy for malocclusion correction, midface tissue resuspension and coronal eyebrow lift to correct soft-tissue ptosis, and submental lipectomy. Bilateral blepharoplasty to minimize tissue excess and scar revision were performed at a subsequent operation. Cephalometric analysis and angiography were performed and blink data collected. RESULTS: Before transplantation, the patient was in class III malocclusion. After transplantation, class I occlusion was obtained; however, the patient subsequently returned to class III occlusion. After skeletal revision, class I occlusion was obtained; however, a corneal blink deficit was noted. Eight months after skeletal revision, blink had improved spontaneously. Angiography revealed collateralization providing retrograde flow from the flap to the recipient. CONCLUSIONS: Although the necessity for revisions is clear, determining which revisions to safely perform and their timing and execution have not been explored. The authors address four distinct categories of revisions, including soft-tissue revision, hard-tissue mismatch, and craniofacial skeleton and dental occlusion. The authors illustrate the success of these revisions and assess their advantages, disadvantages, and relative risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction. PERSPECTIVE: Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P<0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix-loop-helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.International Journal of Oral Science advance online publication, 8 August 2014; doi:10.1038/ijos.2014.46.

BACKGROUND: The study of biomechanics of deformation and fracture of hard biological tissues involving organic matrix remains a challenge as variations in mechanical properties and fracture mode may have time-dependency. Finite element analysis (FEA) has been widely used but the shortcomings of FEA such as the long computation time owing to re-meshing in simulating fracture mechanics have warranted the development of alternative computational methods with higher throughput. The aim of this study was to compare dynamic two-dimensional FEA and moving particle simulation (MPS) when assuming a plane strain condition in the modeling of human enamel on a reduced scale. METHODS: Two-dimensional models with the same geometry were developed for MPS and FEA and tested in tension generated with a single step of displacement. The displacement, velocity, pressure, and stress levels were compared and Spearmans rank-correlation coefficients R were calculated (p<0.001). RESULTS: The MPS and FEA were significantly correlated for displacement, velocity, pressure, and Y-stress. CONCLUSIONS: The MPS may be further developed as an alternative approach without mesh generation to simulate deformation and fracture phenomena of dental and potentially other hard tissues with complex microstructure.

BACKGROUND: It has been reported that titanium-zirconium alloy with 13-17% zirconium (TiZr1317) implants show higher biomechanical stability and bone area percentage relative to commercially pure titanium (cpTi) grade 4 fixtures. PURPOSE: This study aimed to determine whether the higher stability for TiZr1317 implants is associated with higher mechanical properties of remodeling bone in the areas around the implants. MATERIALS AND METHODS: This study utilized 36 implants (n = 18: TiZr1317, n = 18: cpTi), which were placed in the healed ridges of the mandibular premolar and first molar of 12 mini pigs (n = 3 implants/animal). After 4 weeks in vivo, the samples were retrieved, and resin-embedded histologic sections of approximately 100 mum in thickness were prepared. In order to determine the nanomechanical properties, nanoindentation (n = 30 tests/specimen) was performed on the bone tissue of the sections under wet conditions with maximum load of 300 muN (loading rate: 60 muN/s). RESULTS: The mean (+/- standard deviation) elastic modulus (E) and hardness (H) for the TiZr1317 group were 2.73 +/- 0.50 GPa and 0.116 +/- 0.017 GPa, respectively. For the cpTi group, values were 2.68 +/- 0.51 GPa and 0.110 +/- 0.017 GPa for E and H, respectively. Although slightly higher mechanical properties values were observed for the TiZr1317 implants relative to the cpTi for both elastic modulus and hardness, these differences were not significant (E = p > 0.75; H = p > 0.59). CONCLUSIONS: The titanium-zirconium alloy used in this study presented similar degrees of nanomechanical properties to that of the cpTi implants.

Subungual melanoma is a rare but lethal form of melanoma. Amputation at the level of the interphalangeal joint or proximal has been described as appropriate surgical management for all stages of subungal melanoma. In cases of subungual melanoma in situ (SMIS), wide local excision can improve functional and aesthetic outcomes. We reviewed our experience of wide local excision for the treatment of SMIS. Between 2003 and 2010, we treated 9 cases of SMIS. We performed a retrospective review of this series looking at the primary outcomes of recurrence or metastasis. Average age was 40 years (range, 5-65 years). Presenting lesions were on the thumb (5) and index finger (4). All patients underwent definitive reconstruction with a combination of full-thickness skin graft (8) and paronychial advancement flap (6). Reexcision was performed when disease-free margins could not be confirmed. To date, there have been no cases of metastasis or local recurrence in any of our 9 patients (mean follow-up time of more than 4 years). Wide local excision can improve functional and aesthetic outcomes with similar success in rates of local recurrence and metastasis when compared to treatment by amputation in SMIS.

Bone graft materials are utilized to stimulate healing of bone defects or enhance osseointegration of implants. In order to augment these capabilities, various surface modification techniques, including atmospheric pressure plasma (APP) surface treatment, have been developed. This in vivo study sought to assess the effect of APP surface treatment on degradation and osseointegration of Synthograft, a beta-tricalcium phosphate (beta-TCP) synthetic bone graft. The experimental (APP-treated) grafts were subjected to APP treatment with argon for a period of 60s. Physicochemical characterization was performed by environmental scanning electron microscopy, surface energy (SE), and x-ray photoelectron spectroscopy analyses both before and after APP treatment. Two APP-treated and two untreated grafts were surgically implanted into four critical-size calvarial defects in each of ten New Zealand white rabbits. The defect samples were explanted after four weeks, underwent histological analysis, and the percentages of bone, soft tissue, and remaining graft material were quantified by image thresholding. Material characterization showed no differences in particle surface morphology and that the APP-treated group presented significantly higher SE along with higher amounts of the base material chemical elements on it surface. Review of defect composition showed that APP treatment did not increase bone formation or reduce the amount of soft tissue filling the defect when compared to untreated material. Histologic cross-sections demonstrated osteoblastic cell lines, osteoid deposition, and neovascularization in both groups. Ultimately, argon-based APP treatment did not enhance the osseointegration or degradation of the beta-TCP graft. Future investigations should evaluate the utility of gases other than argon to enhance osseointegration through APP treatment.

The human vocal fold is a complex structure made up of distinct layers that vary in cellular and extracellular matrix composition. Elucidating the mechanical properties of vocal fold tissues is critical for the study of both acoustics and biomechanics of voice production, and essential in the context of vocal fold injury and repair. Both quasistatic and dynamic behavior in the 10-300Hz range was explored in this preliminary investigation. The resultant properties of the lamina propria were compared to that of the nearby thyroarytenoid muscle. Er, quantified via quasistatic testing of the lamina propria, was 609+/-138MPa and 758+/-142MPa in the muscle (p=0.001). E' of the lamina propria as determined by dynamic testing was 790+/-526MPa compared to 1061+/-928MPa in the muscle. Differences in E' did not achieve statistical significance via linear mixed effect modeling between the tissue types (p=0.95). In addition, frequency dependence was not significant (p=0.18).