Mechanisms of Soft Tissue Injury.

Soft tissue trauma to the face is challenging to manage due to functional and aesthetic concerns. Management requires careful regional considerations to maintain function such as visual fields and oral competence in periorbital and perioral injuries, respectively. Basic wound management principles apply to facial soft tissue injuries including copious irrigation and tension-free closure. There is no consensus and high-level evidence for antibiotic prophylaxis especially in various bite injuries. Ballistic injuries and other mechanisms are briefly reviewed. Scar revision for soft tissue injuries can require multiple procedures and interventions. Surgery as well as office procedures such as resurfacing with lasers can be employed and will be reviewed.

Reconstruction of Cutaneous Cancer Defects of the Head and Neck.

The goals of cutaneous malignancy reconstruction are to restore the best functional and aesthetic outcome. Reconstruction should aim to restore all defects layers. While local flaps are the mainstay of head and neck Mohs reconstruction, the range of reconstructive options varies from healing by secondary intention to microvascular free tissue transfer.

Comparing Urban Maxillofacial Trauma Patterns to the National Trauma Data Bank©.

OBJECTIVES: We aimed to determine whether certain maxillofacial fracture patterns and injury mechanisms were more prevalent in an urban environment. In addition, we aimed to determine if maxillofacial trauma incidence correlated with income. METHODS: Data was collected from Einstein Healthcare Network and Temple University Health System. These data were compared to the 2016 National Trauma Data Bank© (NTDB©) using chi-square analysis. Multivariate analysis was used to identify correlations between demographic variables and fracture patterns. Sociodemographic data was further characterized utilizing neighborhood mapping. RESULTS: A total of 252 patients from our urban campuses and 14 447 patients from the NTDB© were identified with facial fractures. Maxillofacial trauma patients in the urban population were more likely to be minorities and less likely to be Caucasian compared to the NTDB© (P < .001). Patients in the urban setting were more likely to sustain mandibular and orbital fractures, and less likely to sustain maxillary fractures and multiple fractures (P < .001). Urban maxillofacial trauma patients were more likely to sustain assault and sporting injuries, and less likely to sustain injuries from motor vehicle accidents and self-harm (P < .001). CONCLUSIONS: Maxillofacial trauma patterns and injury mechanisms were shown to be significantly different in an urban environment as compared to national data.

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.

Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas.

Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the ß1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. © 2015 Wiley Periodicals, Inc.

Management of soft palate agenesis in Nager syndrome with an elongated, superiorly based pharyngeal flap.

Nager syndrome, or preaxial acrofacial dysostosis, is associated with aberrant development of the first and second branchial arch structures, as well as abnormal development of the limb buds. It is a rare disorder, and its clinical manifestations have not been completely defined. Absence of the soft palate has been reported in patients with Nager syndrome. In this report we describe the use of an elongated, superiorly based pharyngeal flap for the treatment of severe velopharyngeal insufficiency in a patient with Nager syndrome and absence of the soft palate. We also describe the dysmorphisms associated with Nager syndrome and present a differential diagnosis for the condition.

Prostate cancer metastatic to the larynx: a case report.

Prostate cancer, which is the most common cancer among men, rarely metastasizes to the neck. We report a case of prostatic carcinoma that metastasized to the larynx in a 71-year-old man who presented with hoarseness and shortness of breath. Computed tomography (CT) detected a 2.9 × 3.1 × 2.6-cm mass that extended from the cricoid and arytenoid cartilages into the superior trachea. Findings on histopathology and immunohistochemistry of the laryngeal tumor were consistent with a metastasis of the patient's earlier prostate cancer. CT of the chest later detected a soft-tissue mass in the right paraspinal area and other thoracic pathology that represented metastatic disease. The patient was treated with palliative radiation therapy. As androgen deprivation therapy continues to increase the life expectancy of prostate cancer patients, detection of distant metastases will likely increase, as well. Urogenital cancer metastatic to the head and neck should be considered in the differential diagnosis of laryngeal masses.

Comparison of bone morphogenetic protein-2 and osteoactivin for mesenchymal cell differentiation: effects of bolus and continuous administration.

Current osteoinductive protein therapy utilizes bolus administration of large doses of bone morphogenetic proteins (BMPs), which is costly, and may not replicate normal bone healing. The limited in vivo biologic activity of BMPs requires the investigation of growth factors that may enhance this activity. In this study, we utilized the C3H10T1/2 murine mesenchymal stem cell line to test the hypotheses that osteoactivin (OA) has comparable osteoinductive effects to bone morphogenetic protein-2 (BMP-2), and that sustained administration of either growth factor would result in increased osteoblastic differentiation as compared to bolus administration. Sustained release biodegradable hydrogels were designed, and C3H10T1/2 cells were grown on hydrogels loaded with BMP-2 or OA. Controls were grown on unloaded hydrogels, and positive controls were exposed to bolus growth factor administration. Cells were harvested at several time points to assess osteoblastic differentiation. Alkaline phosphatase (ALP) staining and activity, and gene expression of ALP and osteocalcin were assessed. Treatment with OA or BMP-2 resulted in comparable effects on osteoblastic marker expression. However, cells grown on hydrogels demonstrated osteoblastic differentiation that was not as robust as cells treated with bolus administration. This study shows that OA has comparable effects to BMP-2 on osteoblastic differentiation using both bolus administration and continuous release, and that bolus administration of OA has a more profound effect than administration using hydrogels for sustained release. This study will lead to a better understanding of appropriate delivery methods of osteogenic growth factors like OA for repair of fractures and segmental bone defects.

Maxillofacial injuries and violence against women.

OBJECTIVE: To determine if patterns of facial injuries differed between those of female assault victims with maxillofacial injuries and those of female patients with maxillofacial injuries from other causes. METHODS: We reviewed the medical and dental records of 326 adult female facial trauma patients treated by otolaryngologists and oral/maxillofacial surgeons at the University of Kentucky Medical Center. Information abstracted included date of injury, dates of presentation for medical attention, mechanism(s) of injury, diagnoses, and treatments. RESULTS: While victims of intimate partner violence were more likely to have zygomatic complex fractures, orbital blow-out fractures, and intracranial injuries than were other patients with facial trauma, women assaulted by unknown or unidentified assailants were more likely to have mandible fractures (P = .004). CONCLUSION: These results in conjunction with other presenting circumstances, such as delay in presentation, can assist the surgeon treating patients with maxillofacial injury in recognizing interpersonal violence against women.

In vitro effects of combined and sequential bone morphogenetic protein administration.

OBJECTIVE: To assess the effects of combined and sequential administration of bone morphogenetic protein 2 (BMP-2) and BMP-7 on osteoblastic differentiation compared with administration of single growth factors. DESIGN: In vitro study of osseous differentiation in murine pluripotent cells using assays of extracellular matrix calcification, alkaline phosphatase activity, and expression of osseous markers. Mesenchymal cells were cultured with BMP-2, BMP-7, or a combination of these growth factors or were sequentially exposed to the growth factors. RESULTS: Sequential administration of BMP-2 and BMP-7 resulted in increased extracellular matrix calcification and expression of osteocalcin, whereas all groups treated with BMP up-regulated expression of the osteoblastic transcription factor Runx2/cbfa1, type I collagen, and the inhibitory BMP second messenger Smad6. None of the experimental groups demonstrated increased expression of osteopontin or Smad1, and only cells treated with concurrent administration of BMP-2 and BMP-7 increased Smad5 expression. Alkaline phosphatase activity was increased from baseline only in cells treated with BMP-2 alone. CONCLUSIONS: Culture with BMP-2 and BMP-7, their sequential administration, and their coadministration had variable effects on osseous differentiation in mesenchymal cells. These results demonstrate the need for increased understanding of the role of growth factors and their combinations in bone development and have important implications for the ongoing development of osteoinductive therapies.

Cleft lip and palate.

Patients who have cleft lip or palate face significant lifelong communicative and aesthetic challenges and difficulties with deglutition. Management of patients who have orofacial clefting requires an understanding of the anatomy and pathophysiology associated with clefting and the developmental difficulties encountered by these patients. This article describes current surgical concepts and principles of cleft care. Advances in the embryology and genetics of orofacial clefting are also discussed. It is expected that the care of patients who have clefts will continue to evolve because of advances in the fields of tissue engineering, genetics, and fetal surgery.

Bone regeneration in the rat mandible with bone morphogenetic protein-2: a comparison of two carriers.

OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM RATING: B-2.

Biomechanical evaluation of fixation techniques for bridging segmental mandibular defects.

OBJECTIVE: To compare biomechanical properties of currently available plating systems used to reconstruct segmental mandibular defects. DESIGN: Controlled in vitro investigation. SETTING: Academic medical center laboratory. INTERVENTIONS: Thirty-two polyurethane mandibles were equally divided among 4 groups: mandibles with a 4-cm lateral segmental defect that was bridged with a (1) 3.0-mm locking-screw reconstruction plate, (2) 2.4-mm low-profile reconstruction plate, or (3) 2.4-mm reconstruction plate and (4) uncut (control) mandibles. All plates were contoured and secured to the synthetic mandibles with 4 bicortical screws on either side of the defect. Three constructs from each group were subjected to contralateral-molar single-load-to-failure testing. Mean yield displacement, yield load, and bending stiffness were quantified and compared among the 4 groups. The single-load-to-failure data were used to establish conditions for fatigue testing; such testing was then performed on the remaining 5 samples in each group. Mean cycles to failure were measured and compared among the 4 groups. RESULTS: Mean yield displacement, yield load, and bending stiffness were comparable among the plated groups. Both the 3.0-mm locking-screw and 2.4-mm low-profile reconstruction plate designs withstood 1580 and 1124 times more cycles to failure, respectively (P = .005), than did the control group. The other reconstruction plate was also superior to the unplated controls, offering an 865-fold improvement. CONCLUSIONS: All 3 mandibular fixation device systems tested produce comparable levels of single load to failure biomechanical integrity; however, the higher-profile plating system design offered slightly superior fatigue performance. No differences in performance were observed between the locking and nonlocking designs; neither failed at the screw-substrate interface.

Defect repair in the rat mandible with bone morphogenic protein 5 and prostaglandin E1.

OBJECTIVE: To compare the osteogenic abilities of 2 growth factors (bone morphogenic protein 5 [BMP-5] and prostaglandin E1 [PGE1]) and 2 carriers (collagen/polylactic acid [PLA] and collagen/calcium hydroxyapatite cement [HAC]) in the repair of a rat mandibular body defect. DESIGN: Prospective controlled trial. Subjects Twenty-nine Sprague-Dawley rats. INTERVENTIONS: Critical size defects were created in the bilateral mandibular bodies of the rats. Each hemimandible was assigned to an experimental group. The defects were filled with PLA (group 1), PLA with BMP-5 (group 2), PLA with PGE1 (group 3), HAC (group 4), HAC with BMP-5 (group 5), or HAC with PGE1 (group 6). The control group (group 7) had unfilled defects. The animals were killed after 12 weeks, and the nondemineralized specimens were processed histologically. Stereologic techniques were used to determine the volume fractions of new bone, osteoid, marrow, remaining implant, and fibrous tissue in each defect. RESULTS: The HAC/BMP-5 group (group 5) contained significantly more new bone than the PLA/BMP-5 group (group 2) (P =.02), the HAC and HAC/PGE1 groups (groups 4 and 6) (P =.002), and the control group (group 7) (P<.01). The HAC/BMP-5 group also had less fibrous tissue than the HAC group and the HAC/PGE1 group (P<.001). Groups 5 and 6 had less fibrous tissue than group 7 (P<.01). The groups containing PGE1 demonstrated significantly more osteoid development than the other experimental groups (P<.001). CONCLUSIONS: Inclusion of BMP-5 in an implant with calcium hydroxyapatite cement resulted in the formation of significantly larger fractions of new bone and less fibrous tissue ingrowth than occurred in the other experimental groups. The presence of PGE1 resulted in larger amounts of osteoid deposition, suggesting the potential for delayed bone healing.

Defect repair in the rat mandible with bone morphogenic proteins and marrow cells.

OBJECTIVE: To investigate the ability of a bone growth factor mixture and bone marrow cells to repair a critical size defect of the rat mandibular body. DESIGN: Prospective, randomized controlled trial. SUBJECTS: Thirty-seven male Fischer rats. INTERVENTIONS: Critical size defects 4 mm in diameter were created in the left mandibular bodies of the rats. The defects were filled with a bone marrow cell suspension (group 1), a synthetic bone matrix consisting of bovine collagen and calcium hydroxyapatite cement (group 2), the matrix and marrow cells (group 3), the matrix with 100 micro g of bone growth factor mixture (group 4), or the matrix with bone growth factor mixture and marrow cells (group 5). Animals were killed after 8 weeks, and the nondemineralized specimens were processed histologically. Specimens from group 1 were not processed because there was no grossly appreciable bone regeneration. Stereologic techniques were used to determine and compare the volume fractions and volume estimates of mature bone, new bone, osteoid, marrow, remaining cement, and fibrous tissue in each defect. RESULTS: Volumes of mature bone, new bone, and remaining cement did not differ significantly among the groups (P =.30 for mature bone, P =.17 for new bone, and P =.34 for cement). However, group 4 and 5 specimens contained significantly more osteoid and larger marrow spaces than did the group 2 and 3 specimens (P<.001 for both). The specimens in groups 2 and 3 contained significantly more fibrous tissue ingrowth than did those in groups 4 and 5 (P<.001). CONCLUSION: The synthetic bone substitute containing bone growth factor mixture was effective in stimulating new bone and osteoid development in the rat mandibular model.