In vitro microdistraction of preosteoblasts: distraction promotes proliferation and oscillation promotes differentiation.

Osteoblast biology is influenced in vivo by a 3-dimensional (3D) extracellular matrix that mediates their adhesion and interaction and by a constant state of compressive and tensile forces. To study the role of mechanical stress on osteoblasts in vitro, these parameters must be addressed. Therefore, this study describes the use of a novel, in vitro system that subjects cells to distractive and compressive forces in a 3D environment. This system, termed a microdistractor system, was used to apply linear forces to 3D collagen type I gels containing preosteoblasts. Gels were induced for up to 16 days in osteogenic medium and subjected to either constant linear distraction (distraction gels) or to repeating cycles of distraction and compression (oscillation gels). The effect of these stresses was evaluated over time by measuring proliferation rates, protein synthesis (i.e., cellular activity), and osteogenic differentiation levels. While linear forces in general appeared to increase protein synthesis, force-specific effects on proliferation and differentiation were observed. Specifically, distraction forces appeared to enhance MC3T3 proliferation while distraction/compressive forces appeared to accelerate their osteogenic differentiation program. Therefore, these results suggest that the microdistraction system may be an appropriate in vitro system for the study of mechanobiology in osteoblast phenotype.

Fibrous dysplasia of the zygomaticomaxillary region: outcomes of surgical intervention.

BACKGROUND: Fibrous dysplasia is the most common craniofacial tumor, presenting in both monostotic and polyostotic forms with varying degrees of severity. No consensus exists regarding the surgical management of craniofacial fibrous dysplasia, particularly in the zygomaticomaxillary region. The present study compared long-term outcomes of limited reduction burring versus radical resection of zygomaticomaxillary fibrous dysplasia. METHODS: Patients with craniofacial fibrous dysplasia at the University of California, Los Angeles, Craniofacial Center from 1982 to 2008 were studied based on demographics, treatment, and follow-up data, including examinations, computed tomographic scans, photographs, physician Whitaker scoring, and patient surveys (n=97). Outcomes were compared for zygomaticomaxillary disease treated with radical resection with cranial bone graft reconstruction or limited reduction burring (n=58). RESULTS: Thirty-four percent of patients had monostotic disease, 66 percent had polyostotic disease, 3 percent had McCune-Albright syndrome, and 2.1 percent had malignant degeneration into osteosarcoma. Most patients had surgical treatment (84.5 percent). Of the patients that required optic nerve decompression for vision changes (11.4 percent), most (75 percent) had vision stabilization postoperatively. Differences were recorded in zygomaticomaxillary disease treated with radical resection (63.8 percent) versus reduction burring (36.2 percent) according to age (19.6 versus 14.2 years), complications (13.5 percent versus 4.8 percent), recurrence (66.7 percent versus 24.3 percent), and number of subsequent procedures (2.8 versus 4.0). There were similarities in Whitaker outcome score (1.3±0.3 versus 1.5±0.6) and patient satisfaction (2.7±0.4 versus 2.8±0.3). CONCLUSIONS: Although different approaches have been advocated to treat fibrous dysplasia, the authors' data support a more aggressive management for zygomaticomaxillary disease with radical resection and cranial bone graft reconstruction, especially for more involved disease. CLINICAL QUESTION OF EVIDENCE: Therapeutic, III.

BMP-2 does not influence the osteogenic fate of human adipose-derived stem cells.

BACKGROUND: Recent studies have shown that bone morphogenetic protein (BMP)-2, a potent osteogenic growth factor, in combination with human adipose-derived stem cells can heal critical-sized bony defects. However, whether BMP-2 induces an osteogenic response in the adipose-derived stem cells remains unknown. METHODS: : In vitro calcium production, osteogenic gene expression, and BMP-2 receptor expression on the adipose-derived stem cell surface were analyzed in BMP-2-stimulated adipose-derived stem cells. The cells (2 x 10(7) cells) maintained in osteogenic medium were treated with an initial pulse of BMP-2 for 48 hours or 7 days or were given continuous BMP-2. To assess the response of these cells to BMP-2 in vivo, they (250,000 cells) were seeded into polylactic-co-glycolic acid (PLGA) collagraft scaffolds treated with 5 microg of BMP-2 and implanted into critical-sized femoral rat defects (n = 40). Healing was assessed histologically and quantitated by micro-computed tomography. RESULTS: In vitro treatment of adipose-derived stem cells with BMP-2 revealed decreased ability of the cells to undergo matrix calcification, demonstrated by decreased calcium production and decreased osteogenic gene expression of transcription factor Cbfa-1 and key extracellular proteins. Flow cytometry demonstrated decreased expression of BMP-2 receptors 1a and 1b in osteogenically differentiated adipose-derived stem cells stimulated with BMP-2. In vivo implantation of adipose-derived stem cell-seeded PLGA did not result in healing of critical-sized femoral defects in rodents, whereas implantation of BMP-2-absorbed PLGA, with or without adipose-derived stem cells, consistently healed these defects. CONCLUSIONS: The data suggests that osteogenic differentiation of adipose-derived stem cells is marginally affected by the addition of BMP-2. Consequently, stem cells in combination with BMP-2 may not be a viable strategy for the bony healing.

Intracranial volume and cephalic index outcomes for total calvarial reconstruction among nonsyndromic sagittal synostosis patients.

BACKGROUND: Controversy abounds as to how craniosynostosis affects intracranial volume and whether more extensive procedures achieve superior results. Intracranial volume and cephalic index were evaluated among nonsyndromic sagittal synostosis patients undergoing cranioplasty. METHODS: Twenty-four children with isolated nonsyndromic sagittal synostosis underwent a total calvarial reconstruction. Volume and cephalic index measurements were taken 1 month preoperatively, 1 month postoperatively, and at 1-year follow-up. Data obtained were compared against normative value curves, and interval shifts between curve SD ranges were noted. The absolute percentage difference between the observed intracranial volume or cephalic index and the correlated normative mean value (absolute mean percentages) was calculated for each scan. RESULTS: Preoperatively, intracranial volume for patients younger than 30 months (n = 19) was within the normal range (+/-1 SD), whereas it exceeded 1 SD in all patients older than 30 months (n = 5). Postoperatively and at follow-up, intracranial volume range was unchanged for patients younger than 30 months but was decreased to normal for 60 percent of those older than 30 months. Absolute mean volume percentage showed a small increase from preoperatively for patients younger than 12 months (p < 0.05), no change for patients aged 12 and 30 months, and decreased for patients older than 30 months (p < 0.05). Postoperatively, all patients demonstrated a normal intracranial volume growth rate. As for cephalic index, preoperatively, 92 percent of patients fell below the minimum normal values. At follow-up, 100 percent had a cephalic index in the normal range (p < 0.05). CONCLUSIONS: Nonsyndromic sagittal synostosis results in an age-dependent increased intracranial volume and decreased cephalic index. Total calvarial reconstruction (1) appears to allow for the expansile forces of the growing brain to be distributed and may relieve an underlying abnormality; (2) does not affect postoperative intracranial volume growth rate; and (3) enables normalization of cephalic index.

Formation of in vitro murine cleft palate by abrogation of fibroblast growth factor signaling.

BACKGROUND: A strong association between fibroblast growth factors (FGFs) and palatal anatomy suggest their role in proper palatal development. The purpose of this study was to establish whether fibroblast growth factor signaling is essential for normal palate development, improve the understanding of the biology of palatal fusion, and create a new in vitro cleft palate model. METHODS: Palatal pairs excised from embryonic day 13.5 mouse palatal shelves were divided into three equal groups (n = 18 pairs) and cultured with the nasal side down and their medial edge epithelia in close apposition. Controls received vehicle only (n = 6 pairs) or LacZ recombinant virus (n = 6 pairs). The experimental group (n = 6 pairs) received truncated FGF-R1 recombinant virus with hemagglutinin epitope tag (1 x 10(9) plaque-forming units), which abrogated signal transduction by FGF-R1, FGF-R2, and FGF-R3. Tissue sectioning and staining was used to assess palatal continuity at 96 hours and immunohistochemistry was used to localize expression of the truncated receptors. RESULTS: Both groups 1 (control, vehicle only) and 2 (LacZ) showed complete fusion of palatal shelves after 96 hours in five of six specimens and near fusion in the remaining specimen. Beta-galactosidase staining indicated effective delivery of the LacZ virus to targeted epithelial cells. None of the group 3 specimens (FGF-R1) showed histologic resolution of the medial edge epithelia seam. Immunohistochemistry for the hemagglutinin epitope tag indicated infection by the truncated FGF-R1 virus throughout the epithelium and mesenchyme of the epithelium. CONCLUSION: By abrogating signal transduction by FGF-R1, FGF-R2, and FGF-R3, the authors have demonstrated that such signaling is essential for normal mammalian palate development.

Posterior cranial fossa box expansion leads to resolution of symptomatic cerebellar ptosis following Chiari I malformation repair.

Chiari I malformation occurs when the cerebellar tonsils herniate downward through the foramen magnum into the upper cervical spinal canal. If the posterior fossa craniectomy during corrective surgery leads to excessive enlargement of the foramen magnum, the complication of cerebellar ptosis may result. To treat this difficult problem a posterior cranial fossa box expansion was devised and studied. Patients who developed symptomatic cerebellar ptosis (confirmed by MRI) following cranial vault decompression for Chiari I malformations underwent a posterior fossa box expansion (n=7). This procedure involved coverage of posterior aspect of the enlarged foramen magnum with a split-thickness calvarial bone graft box. The box reconstruction provided separation between the neck musculature, soft tissues from the neural tissue; prevention of cerebellar prolapse; and expansion of the posterior cranial vault. Patients had a mean of 12+/-1 months between initial suboccipital craniectomy and confirmation of symptomatic cerebellar ptosis. Mean age at the time of posterior fossa box reconstruction was 31+/-9 years (range of 14 to 44 years). Preoperative symptoms of headache (7/7, 100%), upper extremity numbness (5/7, 71%) or paresthesias (3/7, 43%), respiratory disturbance (2/7, 29%) and inability to walk (2/7, 29%) improved in all patients postoperatively. At more than 12 month follow-up 6/7 patients (86%) were both disease-free (MRI confirmation) and symptom-free. One out of seven patients had return of headache in a more mild form. Thus, in our patient group the posterior fossa box reconstruction led to resolution of symptomatic cerebellar ptosis following Chiari I malformation repair.

Delayed closure of the hard palate leads to speech problems and deleterious maxillary growth.

BACKGROUND: Hard palate cleft closure has been associated with maxillary hypoplasia. The Schweckendiek procedure offers delayed hard palate closure to avoid early subperiosteal dissection and palatal scarring. This study sought to compare single-stage versus delayed hard palate closure for speech outcome and maxillary growth. METHODS: A retrospective outcome study was performed of unilateral cleft lip and palate patients with either delayed hard palate repair with a pinned-retained speech prosthesis (Schweckendiek repair) (group 1, delayed hard palate repair, 1978 to 1983) or single-stage cleft palate repair (group 2, single-stage repair, 1983 to 1988). Patients with complete records to maturity at the University of Pittsburgh Cleft Palate Craniofacial Center (n = 82, two equal groups of 41 patients) were studied. Comparative data were collected from multidisciplinary evaluations, perceptual speech scores, speech tests, and cephalometric analysis. RESULTS: Single-stage cleft palate repair had a lower fistulization rate (11 percent) compared with delayed hard palate repair (58 percent). It also had better speech outcomes compared with delayed hard palate repair: mean speech score, 3.1 versus 7.8; final speech score, 0.9 versus 2.9; velopharyngeal incompetency, 21 percent versus 66 percent; failed video fluoroscopy or nasoendoscopy, 18 percent versus 52 percent; and need for secondary speech procedure, 20 percent versus 63 percent. Single-stage repair showed less maxillary growth disturbance, with class III malocclusion, 31 percent versus 66 percent; cephalometric SNA, 78.2 versus 74.8; need for Le Fort I advancement, 24 percent versus 42 percent; and amount of maxillary advancement required, 6 mm versus 9 mm. CONCLUSION: The delayed cleft palate repair led to worse speech outcomes; thus, the authors' center abandoned this technique in favor of single-stage repair. In addition, their data showed that the delayed cleft palate repair led to deleterious maxillary growth.

Cranial suture response to stress: expression patterns of Noggin and Runx2.

BACKGROUND: Current theory on normal cranial suture fusion entrusts the dura with the regulatory role. Studies suggest that the dura responds to stress with changes in gene expression. Noggin (bone morphogenetic protein inhibitor) expression is decreased in normal (rat and mouse) cranial suture fusion, but its role in craniosynostosis and the response to stress has not been studied. METHODS: Posterior frontal (fusing) and sagittal (patent) rat cranial sutures were held static, oscillated, or distracted for 10 days in an organ culture microdistraction device beginning at 5 days of age (n = 30 sutures, or 10 sutures per group). The percentage of fusion equaled the score received for bony closure. Noggin, Runx2, and alkaline phosphatase expression was localized by immunohistochemistry for all groups. RESULTS: Both the posterior frontal and sagittal sutures demonstrated a significant (p < 0.05) increase in fusion percentage with oscillation relative to the static control. Noggin was not expressed in the fusing posterior frontal suture but was expressed in the normally patent sagittal suture. Conversely, Runx2 was expressed in the posterior frontal suture but not in the sagittal suture. However, when a mechanical stress was applied, both the posterior frontal and sagittal sutures expressed Runx2 but not Noggin, as in the static fusing suture. CONCLUSIONS: The application of mechanical stress to cranial sutures results in fusion of both the posterior frontal suture and the normally patent sagittal suture. Runx2 is expressed but Noggin is not expressed. Thus, mechanical stress influences sutural fusion and may play a role in craniosynostosis.

Craniofrontonasal dysplasia: a surgical treatment algorithm.

BACKGROUND: Craniofrontonasal dysplasia is a rare, familial X-linked syndrome with coronal synostosis (brachycephaly or plagiocephaly), hypertelorbitism (frequently asymmetric), and extracranial anomalies. Details of the timing and technique of the craniofacial correction have not been well described. The largest series of patients with craniofrontonasal dysplasia treated at a single institution was used for review. METHODS: A review of patients at the University of California, Los Angeles Craniofacial Clinic with the diagnosis of craniofrontonasal dysplasia was performed (n = 21). Data included office, hospital, and operative records; photographs; lateral cephalograms; and three-dimensional computed tomographic scans. Based on surgical outcomes, a treatment algorithm was created. RESULTS: Fourteen patients were female, seven were male, and five had a family history of craniofrontonasal dysplasia (24 percent). Eight patients had unilateral coronal synostosis (plagiocephaly) and 13 had bilateral coronal synostosis (brachycephaly). Eleven patients had asymmetric hypertelorbitism and 10 had symmetric hypertelorbitism. Patients also had cleft lip-cleft palate (10 percent), ear deformities (19 percent), strabismus or esotropia (81 percent), dry frizzy hair (100 percent), syndactyly (14 percent), and nail (100 percent) or other anomalies. After fronto-orbital advancement, no patients had increased intracranial pressure problems or difficulty related to resynostosis. After hypertelorbitism correction, three patients relapsed. Because of this, correction in later patients was delayed until after eruption of permanent maxillary incisors. The mean anterior interorbital distance was reduced in patients from 184 percent to 98 percent of sex-matched controls. CONCLUSIONS: The phenotypic expression of craniofrontonasal dysplasia is described to recognize patients early. A treatment algorithm for craniofrontonasal dysplasia based on timing and technique is offered to decrease the need for revision and improve outcomes.

Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix.

Harvest of the autogenous iliac crest bone graft for an alveolar cleft defect (the gold standard) may cause short- and long-term pain and sensory disturbances. To determine if a tissue engineering technique with similar bone healing results offered decreased morbidity, we compared techniques for postoperative donor site pain. Traditional iliac crest bone graft had more donor site complications compared with both tissue engineering and minimally invasive iliac crest bone graft. With donor site pain, traditional had the most patients with pain and tissue engineering had the least patients with pain at all time points. The mean pain score, including both intensity and pain frequency, was greatest at all time points in traditional and least at all time points in tissue engineering. Closure of alveolar cleft defects with a resorbable collagen sponge and bone marrow stem cells resulted in reduced donor site morbidity and decreased donor site pain intensity and frequency.

Noggin underexpression and runx-2 overexpression in a craniosynostosis rabbit model.

INTRODUCTION: Normal suture fusion has been shown to be driven by the molecular signals elucidated by the underlying dura. However, the pathogenesis of suture fusion in craniosynostosis is not well described. The purpose of our study was to examine the expression patterns of 2 important molecular signals (Noggin and Runx-2) in a cohort of congenital craniosynostotic rabbits to gain a better understanding of suture behavior in craniosynostosis. METHODS: Coronal (fusing) and sagittal (patent) rabbit cranial sutures from a colony of congenitally synostosed rabbits and wild-type (control) rabbits were harvested at a neonatal time point. These sections were then grown in organ culture and harvested for histology at 0, 7, or 14 days of culture. Fusion percentage was then assessed and an overall fusion score was calculated. Expression of Noggin and Runx-2 was then localized by immunohistochemistry and quantified by Western blot analysis. RESULTS: Histology of the wild-type cranial sutures (control) showed suture patency (score of 0%) for all coronal and sagittal sutures at 0 days, 7 days, and 14 days of organ culture. Sagittal sutures of craniosynostotic animals also showed suture patency (score of 0%) at all culture times (0, 7, and 14 days). Of the 18 coronal sutures from the craniosynostotic animals, 8 remained patent and 10 fused. For the coronal sutures that fused, fusion scores of 14%, 41%, and 84% were documented at 0, 7, and 14 days of organ culture, respectively. With immunolocalization, Noggin was found to be expressed in both the dura and suture cells underlying patent sutures, but not in fusing sutures in vitro. Runx-2 was found to be expressed in the dura beneath the suture and suture cells of fusing sutures, not patent sutures. Western blot densitometry confirmed these findings. CONCLUSIONS: Our results suggest that pathologic rabbit coronal sutures progressed toward complete suture fusion in vitro, and expression patterns of Noggin and Runx-2 paralleled that of a well-studied normal suture fusion model.

Top-10 list of herbal and supplemental medicines used by cosmetic patients: what the plastic surgeon needs to know.

BACKGROUND: Widespread use of herbal medications/supplements among the presurgical population may have a negative effect on perioperative patient care. Thus, the authors' goal was to identify the prevalence of such use in a cosmetic surgery patient population compared with use among the general public; to assess physician awareness of proper management of these herbal medications/supplements; and to review the literature to provide rational strategies for managing perioperative patients taking these remedies. METHODS: To assess patient (n = 100) and general public (n = 100) usage rates, open-ended lists of (1) the most common herbal medications/supplements and (2) homeopathic treatments were compiled. Board-certified plastic surgeons (n = 20) were then given the same list of herbs/supplements and surveyed on their awareness of these treatments and perioperative side effects. RESULTS: The usage rate for cosmetic versus public surveys for herbal medicines/supplements was 55 percent versus 24 percent (p < 0.001), with 35 percent versus 8 percent (p < 0.001) engaging in homeopathic practices, respectively. Cosmetic patients' top four herbal/supplements of usage were chondroitin (18 percent), ephedra (18 percent), echinacea (14 percent), and glucosamine (10 percent). The top four used by the general public were echinacea (8 percent), garlic (6 percent), ginseng (4 percent), and ginger (4 percent). The physician survey demonstrated awareness of 54 percent of the listed supplements/herbal medicines, 85 percent of which were not suggested to be discontinued preoperatively, with only ephedra achieving 100 percent physician discontinuation preoperatively. CONCLUSIONS: Herbal medicines and supplements displayed greater prevalence in the cosmetic surgery population than in the population at large. Furthermore, side effects and potential complications warrant addressing these remedies as pharmaceuticals rather than as safe and "natural." Thus, a descriptive "top-10" list with perioperative recommendations was compiled for the plastic surgeon.

Temporomandibular joint bony ankylosis: comparison of treatment with transport distraction osteogenesis or the matthews device arthroplasty.

Temporomandibular joint (TMJ) bony ankylosis with micrognathia is a rare congenital condition that is difficult to treat and may result in recurrence. In a series of affected patients, we compared two new methods of treatment: transport distraction osteogenesis and Matthews Device arthroplasty. All patients had computed tomography scan documented bilateral TMJ bony ankylosis. Group I (transport distraction osteogenesis) underwent distraction advancement of the mandible (for micrognathia) followed by resection of the condyles, recontouring of the glenoid fossas with interposition temporoparietal-fascial flaps, and transport distraction osteogenesis of mandibular rami segments. Group II (Matthews Device arthroplasty) underwent all of the above procedures except for transport distraction osteogenesis. Instead, the Matthews Devices were anchored to the temporal bone and mandibular rami. Hinged arms allowed for motion at the reconstructed TMJ. In both groups, patients underwent extensive postoperative therapy. Preoperative, postoperative, and follow-up lateral cephalograms were obtained, and incisor opening distances were recorded. All patients but one had severe micrognathia (n = 9). For group I (transport distraction osteogenesis), mean age was 6.8 years. and mean advancement was 28.5 mm. For group II (Matthews Device arthroplasty) mean age was 8.2 years, and mean advancement was 23.5 mm. In group I (transport distraction osteogenesis), mean incisor opening was 1 mm preoperatively and 27.5 mm postoperatively; however, it relapsed to 14.3 mm by 12.5 months follow-up (48% relapse). Mean incisor opening in group II (Matthews Device arthroplasty) was 3.9 mm preoperatively and 33.4 mm postoperatively and remained at 30.6 mm after 11.1 months follow-up (8% relapse). One patient in group I (transport distraction osteogenesis) underwent surgical revision because of relapse. Our data showed that for congenital TMJ bony ankylosis both transport distraction osteogenesis and Matthews Device arthroplasty techniques were successful initially; however, the Matthews Device arthroplasty avoided long-term relapse.

Monobloc advancement by distraction osteogenesis decreases morbidity and relapse.

BACKGROUND: Treatment of midface hypoplasia and forehead retrusion with monobloc advancement is associated with significant complications, including meningitis, prolonged intubation, and frontal bone flap necrosis. To see whether distraction of the monobloc segment offered decreased morbidity, the authors compared clinical outcomes of patients who underwent conventional monobloc advancement with those of patients who underwent monobloc distraction. METHODS: Group 1 (conventional monobloc; n = 12) underwent traditional monobloc advancement with bone grafting. Group 2 (modified monobloc; n = 11) did not receive ventriculoperitoneal shunts and underwent the above procedures with placement of a pericranial flap and fibrin glue over the midline defect. Group 3 (monobloc distraction; n = 24) underwent advancement of the monobloc segment by distraction osteogenesis using internal distraction devices. Complications included meningitis, cerebrospinal fluid leak, frontal bone flap loss, and wound infection. Preoperative, postoperative, and follow-up lateral cephalograms were used to assess horizontal changes of the forehead, midface, and maxilla. RESULTS: Group 3 (distraction monobloc) had the lowest complication rate (8 percent), followed by groups 2 (modified monobloc; 43 percent) and 1 (conventional monobloc; 61 percent) (p < 0.05). Group 3 achieved greater advancement (12.6 mm) than did group 2 (9.4 mm) or group 1 (9.1 mm) (p < 0.05). Relapse was least in group 3 (8 percent) compared with groups 2 (67 percent) and 1 (45 percent). CONCLUSIONS: Monobloc advancement by distraction osteogenesis had less morbidity and achieved greater advancement with less relapse compared with conventional methods of acute monobloc advancement with bone grafting. Monobloc distraction is superior to conventional methods of acute monobloc advancement and is an alternative to staged fronto-orbital advancement followed by Le Fort III advancement.

Improved outcomes in cleft patients with severe maxillary deficiency after Le Fort I internal distraction.

BACKGROUND: Correction of severe maxillary deficiency in cleft lip-cleft palate patients often results in undercorrection, relapse, and need for secondary corrective procedures. Le Fort I internal distraction osteogenesis offers an alternative to one-step orthognathic advancement, with advantages of gradual lengthening through scar and earlier treatment in growing patients. METHODS: Patients with cleft lip-cleft palate deformities and maxillary deficiency were divided into three groups treated by Le Fort I advancement: group 1, mild to moderate deficiency (< 10 mm) with conventional orthognathic procedure; group 2, severe deficiency (> or = 10 mm) with conventional orthognathic procedure; and group 3, distraction procedure for severe deficiency (> or = 10 mm) (n = 51). Preoperative, postoperative, and follow-up (> 1 year) lateral cephalogram measurements were compared including angular (SNA and SNB) and linear (Deltax = horizontal and Deltay = vertical) changes. The Pittsburgh Speech Score was used to assess for velopharyngeal insufficiency (score > 3). RESULTS: Results demonstrated that group 1 patients had a mean SNA change from preoperatively (78.7) to postoperatively (83.8), and a horizontal change of 5.0 mm, with no relapse. Group 2 patients had a mean SNA change from preoperatively (76.3) to postoperatively (82.0) and a horizontal change of 7.2 mm, with 63 percent relapse. Group 3 patients had a mean SNA change from preoperatively (74.1) to postoperatively (84.9) and a horizontal change of 16.5 mm, with 15 percent relapse. Thus, for severe maxillary deficiency, the distraction group had 48 percent less relapse than the conventional Le Fort I group. Postoperative speech evaluation showed velopharyngeal insufficiency in the following: group 1, four of 20 patients (20 percent); group 2, nine of 11 patients (82 percent); and group 3, nine of 20 patients (45 percent). CONCLUSION: These data suggest that Le Fort I internal distraction for severe cleft maxillary deficiency leads to better dental occlusion, less relapse, and better speech results.

Favorable morphologic change of preosteoblasts in a three-dimensional matrix with in vitro microdistraction.

BACKGROUND: Distraction osteogenesis has been used to correct hypoplastic and asymmetric bony deformities in the growing patient, yet its underlying cellular mechanisms are poorly understood. Using a new in vitro model, the microdistractor, morphologic properties of preosteoblasts under mechanical strain were studied. METHODS: Mouse calvarial MC3T3 cells were suspended in a polymerized three-dimensional collagen gel and stressed for 14 days as one of three groups (n = 30): (1) distraction (0.5 mm/day); (2) oscillation (1 mm/day for 2 days alternated with 1 mm/day for 2 days); and (3) control (no force). A computer modeling system, KS-300, was used to record cell shape (aspect ratio) and orientation (deviance from axis of stress). RESULTS: In part I of the study, morphologic cellular changes were found to be even throughout different regions of the gel (central versus peripheral, versus different vertical layers), suggesting the force was evenly applied to all cells in the gel. In addition, when linear distraction forces were applied, morphologic change occurred over time, suggesting a morphologic response to the applied stress. In part II of the study, with different forces applied, morphologic changes occurred over time such that linear distraction forces caused cells to elongate and align in a parallel direction to the force, whereas oscillation caused cells to switch from parallel (with distraction) to perpendicular (with compression) orientation relative to the force applied. CONCLUSION: The authors' data suggest that the microdistractor device is an effective in vitro model for studying the cellular response to distraction stresses. It may be used in future studies to optimize clinical methods of distraction.

Genioplasty distraction osteogenesis and hyoid advancement for correction of upper airway obstruction in patients with Treacher Collins and Nager syndromes.

BACKGROUND: Treacher Collins and Nager syndromes may present with mandibular hypoplasia that causes posterior collapse of the tongue base and a decreased oropharyngeal airway. Mandibular distraction and orthognathic advancement are effective treatments to correct the airway, but failure may occur despite achieving class I occlusion. For this select population, the authors propose a novel procedure of genioplasty distraction and hyoid advancement to optimize epiglottal positioning. METHODS: Patients diagnosed with Treacher Collins (n = 5) or Nager syndrome (n = 3) with obstructive sleep apnea or tracheostomy dependency (n = 8) underwent genioplasty distraction and hyoid advancement. Airway outcome was assessed by preoperative and 1-year follow-up comparison of (1) laryngobronchoscopy, (2) sleep studies, and (3) tracheostomy dependency. For genioplasty outcome, three groups were used: group I (distraction genioplasty, syndromic) (n = 8), group II (acute genioplasty, syndromic) (n = 7), and group III (acute genioplasty, nonsyndromic) (n = 10). Lateral cephalogram measurements were used in the preoperative, postoperative, and follow-up periods to assess horizontal and vertical advancement and relapse. RESULTS: Epiglottal position was optimized by the procedure in all patients based on direct endoscopic assessment. All five patients with obstructive sleep apnea had resolution of symptoms, and two of three patients achieved removal of their tracheostomy. Mean advancement for groups I, II, and III was 25, 14, and 8 mm, respectively. Follow-up horizontal advancement for groups I, II, and III were 18, 4, and 6 mm, respectively. Cephalometric measurements showed a horizontal relapse for groups I, II, and III of 10, 62, and 11 percent, respectively. CONCLUSIONS: Data suggest that genioplasty distraction allows for a greater advancement and decreased relapse rate than acute procedures alone; and genioplasty distraction with hyoid advancement is a useful technique for resolution of obstructive sleep apnea or to achieve tracheostomy removal in those syndromic patients who have already undergone mandibular advancement into a class I occlusion.

Osteogenic potentiation of human adipose-derived stem cells in a 3-dimensional matrix.

Adipose-derived stem cells (ADSCs) hold promise for use in tissue engineering. Despite growing enthusiasm for use of ADSCs, there is limited research that has examined their behavior in different in vitro and in vivo systems. The purpose of our study was to evaluate the effect of the extracellular matrix structure and composition on osteogenic differentiation by comparing the osteogenic marker expression of ADSCs grown under 2-dimensional or 3-dimensional cell culture conditions. Group 1 (2-D) included ADSCs raised under conventional cell culture conditions (cells in a 2-D monolayer configuration) (n = 24), and group 2 (3-dimensional) included ADSCs seeded in a collagen gel (cells within a 3-dimensional, biologically active environment) (n = 24). Comparison of ADSC behavior between the 2 groups was analyzed during a 14-day time frame. Osteogenic marker expression (CBFA-1, alkaline phosphatase, osteonectin, osteopontin, Collagen I, and JNK2) was quantified by real-time PCR, and histologic analysis was performed. Histologically, group 1 (2-D) showed cell spreading and deposition of a calcified extracellular matrix. Group 2 (3-dimensional) assumed a disorganized state in the collagen gel, with extension of pseudopodia throughout the matrix. Expression of CBFA-1 was up-regulated immediately in both groups. However, cells in group 2 (3-dimensional) had a more rapid and greater overall expression compared with cells in group 1 (2-D) (250-fold greater at 4 days). At day 14, cells in group 2 (3-dimensional) showed greater expression of all other osteogenic markers than cells in group 1 (2-D) (2.3-fold greater expression of alkaline phosphatase [P < 0.05], 8.4-fold greater expression of osteonectin [P < 0.05], 6.4-fold greater expression of osteopontin [P < 0.05], 2.9-fold greater expression of collagen I [P < 0.05], and 2.5-fold greater expression of JNK2 [P < 0.05]). Our data showed there was a progressive stimulatory effect on ADSCs with regard to osteogenesis when cultured in a 3-dimensional gel compared with a 2-D monolayer.