Joseph K. Williams

Early Decannulation with Bilateral Mandibular Distraction for Tracheostomy-Dependent Patients

Obstructive sleep apnea in the neonatal period may originate from a hypoplastic mandibular framework causing retroposition of the base of the tongue and an inadequate hypopharyngeal space. A tracheotomy in childhood is an effective treatment for obstructive sleep apnea, but it is associated with increased morbidity, management problems, and difficulties in social interaction. Tracheostomy-dependent pediatric patients who underwent mandibular distraction were reviewed to determine the effectiveness of this technique in achieving decannulation. A clinical review was completed to determine the status of the tracheostomy after external, unidirectional distraction in tracheostomy-dependent patients. Expansion of the mandibular framework was analyzed using traditional bony landmarks on predistraction and postdistraction lateral cephalograms. The area of the lower face was analyzed, and changes in the position of the hyoid bone were determined. Four patients with tracheostomies underwent an average of 21.3 mm and 20.8 mm of distraction on the left and right hemimandibles, respectively. The average age at the time of distraction was 2.7 years (range, 2.2 to 3.2 years). All patients underwent successful decannulation at an average of 3.8 months (range, 1.5 to 5.5 months) after completion of distraction. The area of the lower face increased 26.9 percent (range, 12.2 to 53.5 percent) after distraction, and the hyoid bone advanced an average of 14.5 mm (range, 8 to 25 mm). Bilateral mandibular distraction is an effective method of expanding the mandibular framework and concomitantly advancing the base of the tongue. The technique provides a tool for early intervention and decannulation in pediatric patients with indwelling tracheostomies secondary to mandibular deficiencies.

A longitudinal, statistical study of reoperation rates in craniosynostosis

&NA; A prospective, statistical study of reoperation rates was done in the treatment of 167 consecutive children with nonsyndromic and syndromic craniosynostosis over a 6‐year period at Scottish Rite Childrens Medical Center in Atlanta, Georgia. Mean length of follow‐up was 2.8 years, with a range of 3 months to 6 years. Reoperation equal to or exceeding the magnitude of the original procedure occurred in 7 percent of cases. Multiple regression analysis revealed several factors associated with reoperation: Females and children with syndromic synostoses were more likely to require reoperation. Total reoperation rates for syndromic and nonsyndromic synostoses were 27.3 and 5.9 percent, respectively. Age at initial surgery, length of operation, and estimated blood loss did not predict a higher reoperation rate. (Plast. Reconstr. Surg. 100: 305, 1997.)

Controlled multiplanar distraction of the mandible: device development and clinical application.

Distraction osteogenesis has been shown to be an effective method of lengthening and augmenting endochondral bone. It has also been applied effectively in the reconstruction of the membranous bones of the craniofacial skeleton. With the accumulation of clinical experience in mandibular distraction, the differences between endochondral and membranous bone distraction have become apparent, especially in the limitations of uniplanar distraction for the three-dimensional reconstruction of the deficient mandible. Distraction of the mandible in a single plane cannot satisfy fully the functional and structural requirements of the patient with malocclusion as well as deficiency of the skeletal and soft tissue. This study reports the development and clinical use of a multiplanar mandibular distraction device with the ability to achieve linear distraction (Z-plane or sagittal), angular distraction (Y-plane or vertical), and transverse distraction (X-plane or coronal). The device contains two independent gear arrangements attached to two arms that extend from the central unit. Therefore, the trajectory of the regenerated bone may be changed during the distraction process. The device also allows manipulation of the various planes of movement independent of each other. Furthermore, the rotational points for the multiplanar distraction devices are located at a single point; therefore only a single osteotomy and two pin sites are required. The multiplanar distraction device allows the surgeon to customize and contour the dimensions of the distraction process by controlling the trajectory of the translation of the regenerated bone.

Alginate microencapsulation technology for the percutaneous delivery of adipose-derived stem cells

Background:Autologous fat is the ideal soft-tissue filler; however, its widespread application is limited because of variable clinical results and poor survival. Engineered fillers have the potential to maximize survival. Alginate is a hydrogel copolymer that can be engineered into spheres of <200 &mgr;m, thus facilitating mass transfer, allowing for subcutaneous injection, and protecting cells from shearing forces. Methods:Alginate powder was dissolved in saline, and adipose-derived stem cells (ADSCs) were encapsulated (1 million cells/mL) in alginate using an electrostatic bead generator. To assess effects of injection on cell viability, microspheres containing ADSCs were separated into 2 groups: the control group was decanted into culture wells and the injection group was mixed with basal media and injected through a 21-gauge needle into culture wells. Microbeads were cultured for 3 weeks, and cell number and viability were measured weekly using electron and confocal microscopy. To assess effects of percutaneous injection in vivo, twenty-four male nude mice were randomly separated into 2 groups and injected with either empty microcapsules or ADSC-laden microcapsules. Mice were harvested at 1 and 3 months, and the implants were examined microscopically to assess bead and cell viability. Results:A flow rate of 5 mL/h and an electrostatic potential of 7 kV produced viable ADSC-laden microbeads of <200 &mgr;m. There were no differences in bead morphology and ADSC viability between microcapsules placed versus injected into tissue culture plates for up to 3 weeks. Microspheres implanted in a nude mouse model show durability up to 3 months with a host response around each individual sphere. ADSCs remained viable and showed signs of mitosis. Conclusions:ADSCs can be readily cultured, encapsulated, and injected in alginate microspheres. Stem cells suspended in alginate microspheres survive in vivo and are seen to replicate in vitro.

Regulating in vivo calcification of alginate microbeads.

Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium-crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1-6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mm bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification.

Outcome analysis for correction of single suture craniosynostosis using resorbable fixation.

A retrospective review was performed on 63 patients at Childrens Healthcare of Atlanta at Scottish Rite who underwent correction of single-suture craniosynostosis using a resorbable fixation system. Included in the series were 24 patients with metopic synostosis, 15 with sagittal synostosis, and 24 with unicoronal synostosis. The average age at operation was 22.7 months (range: 2.8 months–18 years), and mean follow-up time was 30.7 months (range: 7.1–10 years). Reoperation equal to or exceeding the magnitude of the original procedure occurred in 4.76% of the patients. This was comparable to the reoperation rate observed at our institution using traditional fixation systems. Minor complications related to the use of resorbable plates were also identified, and the final outcome for single-suture synostosis was favorable. Results suggest that resorbable plates and screws are as effective as titanium-based systems in the treatment of single-suture synostosis.

Single-stage craniofacial distraction using resorbable devices.

We report on the use of a new type of internal bone distraction devices designed for craniofacial applications. These resorbable devices allow a single operative procedure for device placement, eliminating the need for a second open operative procedure for hardware removal. We report on three models of resorbable devices. The midface orbital frontal device was used for midface and monoblock advancement. The mandibular adolescent device was used in older children and adolescents. In neonates and young children, the mandibular infant device was used. Twenty-one patients (9 female, 12 male) aged 6 days to 15 years (mean = 53 months) underwent bony expansion of the craniofacial skeleton over a 2-year period. A total of 39 devices were implanted: 32 in the mandible, 3 in the maxilla alone, and 4 in the maxilla and frontal bones. Expansion distances ranged from 15 to 30 mm. Expansion took place at 1 to 2 mm/d. Latency periods ranged from 48 to 72 hours. There were no device structural failures and no major complications.

Midface distraction to alleviate upper airway obstruction in achondroplastic dwarfs.

OBJECTIVE The use of midface distraction in patients with achondroplasia and upper airway obstruction secondary to midface hypoplasia has not been reported. In this report, we review the treatment of two patients with severe midface hypoplasia and obstructive sleep apnea secondary to achondroplasia using midface distraction osteogenesis. DESIGN, SETTING, AND PATIENTS Two patients with achondroplastic dwarfism and midface hypoplasia with airway obstruction were treated in a tertiary referral center for craniofacial disorders. RESULTS AND CONCLUSIONS Both patients had their tracheostomies decannulated after midface distraction of 25 mm. Midface distraction osteogenesis is useful to alleviate upper airway obstruction from midface hypoplasia seen in achondroplasia.

Rapidly polymerizing injectable click hydrogel therapy to delay bone growth in a murine re-synostosis model.

Craniosynostosis is the premature fusion of cranial sutures, which can result in progressive cranial deformations, increased intracranial pressure, and restricted brain growth. Most cases of craniosynostosis require surgical reconstruction of the cranial vault with the goal of increasing the intracranial volume and correcting the craniofacial deformities. However, patients often experience rapid post-operative bone regrowth, known as re-synostosis, which necessitates additional surgical intervention. Bone morphogenetic protein (BMP) inhibitors have tremendous potential to treat re-synostosis, but the realization of a clinically viable inhibitor-based therapeutic requires the development of a delivery vehicle that can localize the release to the site of administration. Here, we present an in situ rapidly crosslinking injectable hydrogel that has the properties necessary to encapsulate co-administered proteins and demonstrate that the delivery of rmGremlin1 via our hydrogel system delays bone regrowth in a weanling mouse model of re-synostosis. Our hydrogel is composed of two mutually reactive poly(ethylene glycol) macromolecules, which when mixed crosslink via a bio-orthogonal Cu free click reaction. Hydrogels containing Gremlin caused a dose dependent inhibition of bone regrowth. In addition to craniofacial applications, our injectable click hydrogel has the potential to provide customizable protein, small molecule, and cell delivery to any site accessible via needle or catheter.

Controlled multiplanar distraction of the mandible, Part II: Laboratory studies of sagittal (anteroposterior) and vertical (superoinferior) movements.

The application of distraction osteogenesis in craniofacial surgery has significantly altered the treatment of congenital mandibular deficiencies. However, evaluation of results in both animal studies and clinical cases has revealed deficiencies, particularly in two areas. First, distraction using a uniplanar device in an anteroposterior direction can result in a persistent anterior open bite. Second, the lateralization of the distracted hemimandible was often limited, with insufficient incremental gain in the bigonial distance. To overcome these shortcomings, a multiplanar distraction device was developed and tested in the canine model. This report details canine studies addressing the first problem: combined anteroposterior or sagittal (z-axis) and superoinferior or vertical (y-axis) movements. Six dogs underwent bilateral mandibular distraction with an external (extraoral), multiplanar device and completed sagittal plus vertical distraction. Evaluation included clinical examination (facial form, jaw position, and occlusion), photography, cephalograms (posteroanterior, basilar, and lateral), three-dimensional computed tomography reconstructions, and examination of dry skulls. The dogs averaged 18.5 mm (range, 15–20 mm) of sagittal distraction and 41.0° (range, 21–50°) of vertical distraction. Marked anterior open bites were produced after vertical distraction secondary to premature contact of the maxillary and mandibular molars. Distraction in the vertical direction also had the additive effect of increasing the sagittal gains by approximately 5% to 10%. In conclusion, a multiplanar distraction device (with the potential for distraction in three planes) was effective in increasing mandibular anteroposterior thrust (sagittal distraction) and also in creating an anterior open bite (vertical or superoinferior distraction). Vertical distraction probably requires bilateral osteotomies to obtain optimal results. The preliminary gains in sagittal length are modified (reduced or increased) after distraction in a second plane (vertical and horizontal). Specifically, vertical distraction in the inferior direction (creating an open bite) also leads to isolated increases in the anteroposterior plane. Conversely, vertical distraction in the superior direction (closing an open bite), as seen in a human malocclusion, may lead to isolated decreases in the anteroposterior plane, but this question remains to be investigated in the laboratory.