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ABSTRACT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is gaining popularity in craniofacial applications. Calvarial defects are, under normal circumstances, subjected to only minimal levels of the biomechanical stresses known to play an important role in osteogenesis, yet regenerated calvarial bone must be capable of withstanding traumatic forces such that the underlying neurocapsule is protected. The aim of this study is to, for the first time, assess the biomechanical properties of calvarial bone regenerated with derivations of a commercially available rhBMP-2-based system. Standardized calvarial defects were created in 23 adult male canines. These defects were treated with rhBMP-2 on one of several carriers. After 24 weeks, the biomechanical properties of the rhBMP-2-generated bone were compared to those of controls with a modified punch-out test (Bluehill 2; Instron, Norwood, Mass) and compared using a paired nonparametric analyses (SPSS, 17.0, Chicago, Ill). In a previously published report, defects across all the rhBMP-2 therapy groups were observed to have a mean rate of 99.5% radio-opacity at 24 weeks indicating nearly full bony coverage of the calvarial defect (compared to 32.7% in surgical controls). For ultimate load, ultimate energy, and first peak energy, there were significant differences (P < 0.05) with the control native bone having more robust biomechanical properties than the rhBMP-2-generated bone. We conclude from these findings that rhBMP-2-generated calvarial bone is significantly less protective against trauma than native bone at 6 months. Further investigation is required to assess the efficacy of rhBMP-2 in healing calvarial defects in the longer term.
Annals of plastic surgery 05/2013; · 1.29 Impact Factor
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ABSTRACT: : Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be an effective therapy in the acute calvarial defect wound and in calvarial defects complicated by chronic scar. The authors compared the effectiveness of rhBMP-2 with the accepted standard of autologous graft for repair of irradiated calvarial defects.
: Nineteen adult New Zealand White rabbits underwent subtotal calvariectomy. Four days postoperatively, animals received 15 Gy to their wound. Six weeks postoperatively, scars were débrided and defects reconstructed in one of four groups: empty (n = 3), vehicle (buffer solution/absorbable collagen sponge; n = 3), cryopreserved autograft, (n = 3), or rhBMP-2 repair (rhBMP-2/absorbable collagen sponge, n = 10). Animals underwent computed tomography imaging at 0, 2, 4, and 6 weeks, followed by euthanization and histological analysis. Percent healing was determined and a 4 × 3 mixed model analysis of variance was performed on healing versus treatment group/postoperative time.
: According to radiopacity, rhBMP-2/sponge and autografts were statistically equivalent, with 99 and 89 percent healing at 6 weeks. Empty and vehicle treatment groups, with 35 and 34 percent healing, were inferior to the rhBMP-2/sponge and autograft groups (p < 0.05). Histologically, bone in the surgical control (autograft) group was less cellular and trabecular than bone formed after rhBMP-2/sponge treatment.
: rhBMP-2 therapy was as effective in reconstructing calvarial defects in the unfavorable irradiated wound as in the acute, favorable calvarial wound. Compared with cryopreserved autologous graft, rhBMP-2-regenerated bone resulted in equal defect coverage, similar thickness, and greater cellularity. Further studies are necessary to demonstrate the long-term viability and remodeling rhBMP-2/sponge-generated bone.
Plastic and reconstructive surgery 11/2012; 130(5):643e-50e. · 2.74 Impact Factor
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ABSTRACT: Animal models of bone reconstruction have shown recombinant human bone morphogenetic protein 2 (rhBMP-2) to be an effective therapy in the acute calvarial defect wound. The purpose of this study was to compare the effectiveness of rhBMP-2 in a rabbit model of an unfavorable scarred calvarial wound with the criterion standard of autograft.
Nineteen adult New Zealand white rabbits underwent subtotal calvariectomy. After 6 weeks of healing and normal scar formation, these animals underwent reoperation for scar debridement and assignment to 1 of 4 therapeutic groups. Animals were assigned to an empty control group (no treatment, n = 3), vehicle control group (neutral buffered solution on an absorbable collagen sponge [ACS], n = 3), surgical control group (cryopreserved autograft, n = 3), or an experimental treatment group (rhBMP-2 on an ACS, n = 10). All animals underwent computed tomography imaging at 0, 2, 4, and 6 weeks after secondary reconstructive surgery. At 6 weeks, all animals were killed, and the defects were examined histologically. Percentage of healing of each defect was determined, and a 4 × 3 mixed-model analysis of variance was performed on healing as a function of time and therapy.
Based on measures of defect radiopacity, the treatment group (rhBMP-2/ACS) and surgical control group (autograft) were statistically equivalent with 98% and 83% healing, respectively, at 6 weeks. The empty control and vehicle control groups were inferior to the treatment group (rhBMP-2/ACS) and surgical control (autograft) groups at each timepoint (P < 0.05). Histologically, bone in the surgical control (autograft) group was less trabecular and less cellular than the bone formed in the experimental treatment group (rhBMP-2/ACS).
Compared with historical controls, rhBMP-2 therapy was as effective in reconstructing calvarial defects in the unfavorable scarred wound as in the acute favorable calvarial wound. When compared with cryopreserved autograft, rhBMP-2-regenerated bone showed equal defect coverage and similar bone thickness with varying bony architecture.
The Journal of craniofacial surgery 03/2012; 23(2):410-4. · 0.81 Impact Factor
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ABSTRACT: Some of the most problematic craniofacial injuries in pediatric plastic surgery are large calvarial defects in children who have passed the age of maximal dural osteogenic potential and yet are too young to yield split calvarial grafts. Porous polyethylene (Medpor; Porex) is an alloplastic material that can be customized to precisely match a cranial defect. We present a clinical series that demonstrates successful use of porous polyethylene cranioplasties in large pediatric cranial defects.
From 2007 to 2009, 9 pediatric patients underwent custom-made porous polyethylene cranioplasties for large calvarial defects. Descriptive statistical analyses were performed on the cause of the defects, time to cranioplasty, size of defect, reconstruction technique, and postoperative healing.
A total of 5 boys and 4 girls, with a mean age of 6.8 years, underwent 9 cranioplasties incorporating custom porous polyethylene implants. Initial pathologic findings included 7 patients with traumatic brain injuries, 1 patient with intractable seizures, and 1 patient with brain cancer. Initially, each patient had a craniectomy followed by replacement of the frozen bone "flap." All patients experienced either infection or resorption of the bone leading to a permanent defect. The mean defect size was 152 cm. The mean delay between the removal of failed bone "flap" and the final implant cranioplasty was 6.8 months. At the last follow-up, which averaged 3.6 months, all patients had stable wounds with acceptable cranial contour.
For pediatric large-scale calvarial defects, custom-made porous polyethylene implants can be safely used for cranioplasty. Tissue expansion and acellular dermal matrix were useful tools to help augment the soft tissues of the scalp before cranioplasty to prevent complications of implant extrusion and wound breakdown.
The Journal of craniofacial surgery 01/2012; 23(1):67-70. · 0.81 Impact Factor
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ABSTRACT: For a population of adolescents, gynecomastia is a persistent problem. Occurring during a critical period in the formation of self-image and gender identity, this gender-incongruent process may disrupt normal psychological development. This study was designed to identify the prevalence of psychological disturbances in young male patients presenting with symptomatic gynecomastia to determine whether psychological examination should be included as a routine portion of this patient population's treatment.
From 2002 to 2009, patients aged between 10 and 18 presenting to our institution for idiopathic adolescent gynecomastia were recruited to participate in a retrospective cohort study. All patients underwent psychological interviews conducted by the same clinical psychologist (C.W.) and were examined using the following metrics: the Children's Depression Inventory, the Multidimensional Anxiety Scale for Children, and the Child Behavior Checklist. All patient scores were compared against population norms.
Twenty-four patients between the ages of 12 and 18 were observed. Compared with the general population, measures of anxiety, depression, and social phobia were significantly elevated in patients with gynecomastia; 100 percent of patients with gynecomastia received a Diagnostic and Statistical Manual of Mental Disorders-IV diagnosis.
Idiopathic adolescent gynecomastia is a psychological threat to normal self-esteem and sexual identity. Patients presenting with this condition likely suffer an adjustment disorder subsequent to this anatomic stressor. Surgeons should strongly consider referring their patients with gynecomastia for psychological evaluation and treatment as an adjunct to successful surgical management of this condition. Future studies examining the postoperative effects on psychological health both with and without psychological treatment will be of great interest to treating physicians.
: Risk, IV.
Plastic and reconstructive surgery 09/2011; 129(1):1-7. · 2.74 Impact Factor
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ABSTRACT: Objectives : Craniosynostosis affects 1 in 2000 to 3000 live births and may result in craniofacial and neural growth disturbances. Histological data have shown that thick collagenous bundles are present in the sutural ligament, which may tether the osteogenic fronts, resulting in premature fusion. The hormone relaxin has been shown to disrupt collagen fiber organization, possibly preventing craniosynostosis by relaxing the sutural ligament and allowing osteogenic fronts to separate normally and stay patent. This study tested this hypothesis with a rabbit model of delayed-onset coronal suture synostosis. Methods : A total of 18 New Zealand White rabbits with craniosynostosis were randomly assigned to one of three groups: sham control, protein control (BSA), relaxin treatment. After initial diagnosis, sham surgery, BSA, or relaxin was delivered to the fusing coronal suture in a slow-release (56-day) collagen vehicle. Longitudinal radiographs and body weights were collected at 10, 25, 42, and 84 days of age, and sutures were harvested for histology. Results : Relaxin-treated animals had more disorganized intrasuture content than control groups. These specimens also appeared to have relatively wider sutures ectocranially. There were no significant differences in relaxin-treated animals for all craniofacial growth measures, or suture separation compared with controls. Conclusions : These data do not support our initial hypothesis that the use of relaxin may rescue sutures destined to undergo premature suture fusion. These findings suggest that collagen fiber arrangement may not be important for suture fusion. This protein therapy would not be clinically useful for craniosynostosis.
The Cleft Palate-Craniofacial Journal 07/2011; 49(5):e46-54. · 0.82 Impact Factor
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ABSTRACT: Although the use of preoperative antibiotics has been proven effective, the value of postoperative antibiotics in the setting of mandibular fracture remains in question as does the appropriate duration of therapy.
A retrospective study of all patients 18 years and older who presented with mandibular fractures to St Louis University Hospital between December 2001 and July 2006 was conducted. Collected variables included age, injury severity score, fracture type and location, preoperative antibiotic administration, antibiotic type, duration of antibiotic course, and postoperative infection. Infections were statistically compared with each.
Of 253 identified patients, 197 qualified for study inclusion. A total of 9 postoperative infections were documented. When comparing individuals with postoperative infection to those without, age was the only significant difference between infected and uninfected groups, with older patients more likely to acquire infection. Injury severity score, fracture type, duration of antibiotic course, and antibiotic type were not significantly different.
Our findings suggest that patient factors make a greater contribution to postoperative infection when compared with iatrogenic factors in the treatment of mandibular fractures. We found no evidence to support prolonged postoperative antibiotic therapy. Our findings bring into question the need for postoperative antibiotics for the treatment of mandibular fractures.
The Journal of craniofacial surgery 07/2011; 22(4):1375-7. · 0.81 Impact Factor
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ABSTRACT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy shown to be an effective means of generating bone formation in multiple clinical settings. However, the optimum dose and delivery of rhBMP-2 to the calvaria are undetermined. The aim of the authors' study was to investigate the use of rhBMP-2 in addressing calvarial defects in a large-animal model through a variety of modifications to this U.S. Food and Drug Administration-approved therapy.
Twenty-three adult canines underwent the creation of a standard calvarial defect and received either no treatment, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with corticocancellous chips, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules, or 0.4 mg/ml rhBMP-2 in a compression-resistant matrix carrier. Direct comparisons of defect radiopacity were performed at 0, 8, 16, and 24 weeks postoperatively before the animals were euthanized. All specimens were evaluated qualitatively with histology.
Surgical control animals had an average defect radiopacity of 32.7 percent at study completion compared with an average of 99.95 percent across all treatment groups. Ectopic bone formation was found consistently in all treatment groups with varying degrees of severity. Regenerated bone thickness, compactness, and organization varied qualitatively between groups.
Treatment with 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules showed the least amount of ectopic bone formation and the most compact bone formation within the defect, and produced reasonably consistent bony thickness across the defect. Future studies should focus on spatial regulation of rhBMP-2 to minimize unwanted bone formation.
Plastic and reconstructive surgery 05/2011; 127(5):1865-73. · 2.74 Impact Factor
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ABSTRACT: We report a case of an 82-year-old female with an anomalous left inferior vena cava. The left inferior vena cava ascends parallel and to the left of the descending abdominal aorta. At the level of the celiac trunk, the inferior vena cava courses anteriorly and to the right to reach the posterior surface of the liver. The patient also suffers from chronic mild postprandial abdominal pain. It is possible that position of inferior vena cava anterior to the aorta, at the level of the celiac trunk, may lead to intermittent celiac artery compression syndrome (Dunbar syndrome).
Clinical Anatomy 03/2011; 24(2):262-5. · 1.29 Impact Factor
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ABSTRACT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy effective at generating bone formation. In pediatric patients for whom other therapeutic options have been exhausted, rhBMP-2 is used off-label to address problematic bony defects. In the skeletally immature patient, the safety of rhBMP-2 therapy remains uncertain. Experiments are needed that investigate the effect of rhBMP-2 on growth and development in clinically relevant models.
Ten juvenile rabbits underwent creation of a parietal skull defect that was treated with either 0.2 mg/cc rhBMP-2/absorbable collagen sponge or a neutral buffer solution/absorbable collagen sponge. Amalgam markers were placed at suture confluences to track suture separation and skull growth. Cranial growth was assessed radiographically at 10, 25, 42, and 84 days of age. Means and standard deviations for the various craniofacial growth variables were calculated and compared. Mean differences were considered significant for values of p < 0.05. At 84 days, sutures were analyzed by means of micro-computed tomographic scanning and histologic staining.
Treatment with rhBMP-2 resulted in fusion of the coronal sutures bilaterally, with variable fusion of the sagittal suture by cephalometric, radiographic, and histologic analysis. There were statistically significant changes to coronal suture growth, sagittal suture growth, skull height, craniofacial length, and intracranial volume (p < 0.05).
The use of rhBMP-2 in this juvenile animal model resulted in skeletal changes that may be undesirable in a clinical setting. The appearance of these fused sutures suggested a direct effect of rhBMP-2. Further work is required to limit the effect of rhBMP-2 to the target defect when used in the immature skeleton.
Plastic and reconstructive surgery 03/2011; 127(3):1173-81. · 2.74 Impact Factor
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ABSTRACT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge has been shown to induce the healing of acute, primary, large-scale calvarial defects in rabbits. However, clinical circumstances often require the reconstruction of a previously infected and chronically scarred wound. This study was designed to evaluate the efficacy of rhBMP-2/absorbable collagen sponge to improve healing in the previously infected, unfavorable calvarial defect model.
Subtotal defects were made in the calvariae of 15 adult New Zealand White rabbits. The bone flap was inoculated with Staphylococcus aureus and replaced in situ. After a 2-week infection period, animals underwent bone flap removal and a 10-day course of antibiotic therapy. On postoperative day 42, the defect was exposed and treated with (1) no intervention/control (group 1; n = 5), or (2) absorbable collagen sponge with 0.43 mg/ml of rhBMP-2 (group 2; n = 10). Bone growth was analyzed with serial computed tomographic imaging and postmortem histology. Percentage bone healing was compared between groups using the t test.
The treatment group (group 2) demonstrated statistically more healing (55.6 percent) compared with the control group (group 1) (29 percent; p < 0.01). However, rhBMP-2-induced bone was not histologically or radiographically similar to native bone, lacking both continuity and a well-defined diploic space.
These data suggest that rhBMP-2-treated collagen sponges may be useful for the repair of calvarial defects following infection. However, the osseous healing observed in this study was significantly less than previous reports in acute, noninfected models and was dissimilar to native bone. Further work is needed to optimize treatment of the previously infected calvarial wound with rhBMP-2.
Plastic and reconstructive surgery 02/2011; 127(2):588-94. · 2.74 Impact Factor
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ABSTRACT: Supernumerary cranial sutures represent a rare cause of plagiocephaly. In the case of an extra suture dividing the parietal bone, the presenting features are often inconsistent with the typical presentation of deformational or synostotic plagiocephaly. Disagreement exists as to how the presence of this suture affects the shape of the skull. We present a case of a supernumerary suture in the parietal bone leading to plagiocephaly and discuss the role this suture plays in cranial growth.
The Journal of craniofacial surgery 01/2011; 22(1):355-8. · 0.81 Impact Factor
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ABSTRACT: Suture reformation after strip craniectomy for nonsyndromic sagittal synostosis remains an inconsistent and underreported phenomenon. Although several theories have been proposed to account for the fate of the cranial defect, no explanation accurately matches clinical experience with the appearance of reformed sutures, ectopic sutures, and complete defect ossification postoperatively.
We review the case of a 7-year-old boy who formed a parasagittal suture at the defect margin after strip craniectomy for nonsyndromic sagittal synostosis. We review the literature and the clinical experiences of previous authors.
The pathogenesis of suture reformation and the biomechanical forces shaping suture formation are still poorly understood. Previous reports of postoperative suture reformation offer inconclusive evidence as to whether a pathologic suture, an abnormal cranial base, or a combination of biomechanical forces plays the larger role. It remains an open question as to whether a single underlying mechanism can explain suture reformation or if there are instead multiple causes.
The Journal of craniofacial surgery 01/2011; 22(1):66-7. · 0.81 Impact Factor
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ABSTRACT: Case series.
To illustrate the use of acellular dermal matrix (ADM) in treatment and prevention of exposed vertical expandable prosthetic titanium rib (VEPTR) implants.
In the pediatric population with severe kyphoscoliosis, VEPTR is an effective tool during growth for the correction of ribcage deformity. Prolonged VEPTR therapy can result in wound breakdown, implant exposure, and infection. Treatment includes the use of prolonged antibiotics, muscle flaps, and, when salvage fails, removal of the VEPTR. The use of ADM in the treatment and prevention of VEPTR exposure has not been previously described.
Between January 2002 and January 2010, eight patients who underwent placement of ADM for the treatment and prevention of exposed VEPTR devices were identified. Their records were reviewed for diagnosis, sex, age of patient at initial VEPTR placement, position of VEPTR placement, number of VEPTR expansions, wound complications, ADM use, adjunct procedures, and length of wound follow-up.
ADM was used in eight patients. In five patients ADM was used for compromised soft tissue overlying the VEPTR and threatened exposure of the hardware. In these cases, subsequent expansions occurred without incident and the wound remained stable with an average follow-up of 7.6 months. In three patients, ADM was used for exposed VEPTR hardware secondary to wound breakdown. Average follow-up was 3.3 months. In two of the three cases of exposed and contaminated hardware, stable soft tissue coverage was achieved and continued VEPTR therapy was achieved. One of the three cases of exposure involved infected and prominent hardware with purulence. This patient failed to clear the infection and required complete device removal.
ADM can treat and prevent exposed VEPTR, allowing subsequent VEPTR expansions and minimizing the need for muscle flap coverage and/or implant removal and replacement.
Spine 01/2011; 36(8):E563-7. · 2.08 Impact Factor
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ABSTRACT: Current methods of scalp reconstruction with complicating osteomyelitis of underlying bone require excision of deficient tissue and a staged reconstruction for ultimate coverage of the defect. Our group proposes a novel use of acellular dermal matrix (ADM) to preserve these deficient areas without the need for excision or staged management of osteomyelitic calvaria.
From 2003 to 2008, 3 patients underwent scalp reconstruction with ADM at our facility. Elevation of the scalp for secondary operations in each case showed full incorporation of the ADM. Follow-up ranging from 12 to 36 months showed a healed scalp with preserved hair-bearing skin in all cases.
Scalp regeneration with ADM has specific advantages that include preservation of hair-bearing scalp, maintenance of distinct tissue planes for later reconstruction, absence of a donor site, and the alleviation of tissue expansion. This technology may represent an immediate solution for difficult scalp defects that would otherwise require staged complex reconstruction.
The Journal of craniofacial surgery 03/2010; 21(2):605-7. · 0.81 Impact Factor
