Faculty Bibliography

New methods of manufacture have enabled the creation of novel dosage forms with unique rapid-dispersion properties. This study combines one such technique with a statistical experimental design to develop dosage forms from captopril, an angiotensin-converting enzyme inhibitor used to treat cases of hypertensive emergency. The TheriForm process, a novel microfabrication technique, was used to build the dosage forms in a layer-by-layer fashion. Three key formulation factors were chosen for the design of experiments. A modified central composite design (Box-Behnken design) was used to maximize the efficiency of the experiments. A total of 13 distinct formulations were fabricated and tested, using mannitol as the bulk excipient. In addition, three replicates of the center point were tested to assess variability and experimental error. These formulations were tested for speed of dispersion (flash time), active content, hardness, friability, and moisture absorption. Regression analysis was performed to fit data responses to quadratic equations. Excellent dose accuracy (95% to 102% of target) and content uniformity (between 1.03% to 2.84%) were observed from all experimental formulation batches. As expected, the choice of powder additive (maltitol, maltodextrin, polyvinyl pyrrolidone), level of additive (2.5% to 7.5%), and saturation level of the binder liquid (45% to 65%) were all found to be significant factors for the TheriForm process. The regression analysis suggested that a rapidly dispersing dosage form of optimal physical properties would be obtained when a powder mixture of mannitol (97.5%) and maltitol (2.5%) is used at a saturation level of 45%. In conclusion, rapidly dispersing captopril oral dosage forms were successfully fabricated and tested. A wide range of physical properties, flash time, and hardness, were determined experimentally, and the effects of key formulation factors were identified

Granular medical-grade calcium sulfate hemihydrate (MGCSH) and negatively charged dextran beads (DB) were evaluated both separately and in combination in cranial defects. Thirty-six rats received bilateral parietal inlay reconstructions using MGCSH, MGCSH plus DB, or DB alone or the defects were left unfilled. Postoperative evaluation at 45, 90, and 135 days was done by visual inspection, caliper measurements of defect thickness, and histologic examination. The best fibro-osseous repair of the defects occurred with the use of MGCSH in combination with DB. Repair tissue, which was confluent with the adjacent cranium, was noted to have good thickness, and a high bone content. By contrast, defects repaired with either DB or MGCSH alone had poorer quality repair tissue, with concavities, voids, bead migration, decreased thickness, and minimal bony replacement/ingrowth. Unfilled control defects showed only a thin, friable, translucent connective tissue layer of repair. No method produced complete bony closure

An alternative approach to the management of free fat transplantation resorption was evaluated in a rat facial model. Fat grafts obtained from the inguinal region were transferred to subcutaneous lateral facial sites in 20 animals. The grafts were mixed with either basic fibroblast growth factor (bFGF) alone or dextran beads that had been pretreated with bFGF. The grafts were then compared by weight and histology at 1 and 6 months postoperatively. Although graft weights were nearly comparable at 1 month, substantial differences were seen at 6 months, with the bead-containing grafts exhibiting near complete weight maintenance and better overall graft form. Histologically, the bead-containing grafts had extensive intercellular collagen formation and a heterogeneity of adipocyte cell sizes, particularly after 1 month. These findings suggest that the addition of cell-specific bioactive peptides that affect either the preadipocyte cell line and/or the fibroblastic components of the recipient site improve postoperative fat graft weight maintenance. Delivery of the biochemical agent appears to require a carrier system to exert its effects

A study was undertaken to evaluate the effects of nerve growth factor (NGF), which had previously demonstrated bone formation around mandibular nerve regenerates, on resorption of onlay bone grafts to the rabbit skull. Iliac grafts were onlayed on the parietal bone bilaterally and immobilized with wire ligatures in 15 animals. NGF and a control solution were introduced into the grafts through subcutaneous osmotic pumps. After 60 days, graft survival was compared by weights, histology, and fluorochrome labels. NGF-treated grafts were characterized by an average of 88.4% weight retention, preservation of the outer cortical plate with firm fixation to the underlying calvarium, and fluorescent labels localized to the inner cortex. Conversely, control grafts had an average weight retention of 42.8% (p < 0.01), nearly complete outer cortical plate loss with increased mobility of the residual inner cortex, and a lack of fluorescence in any part of the grafts. Despite the incongruous name, NGF exhibited a beneficial effect on onlay bone graft volume maintenance in this study. Although the mechanism and the long-term effects are unknown, inhibition of graft resorption rather than enhancement of bone formation is suggested

The classification of giant cell lesions of the maxillofacial skeleton is one that remains controversial. Classifying giant cell lesions of the jaw as granulomatous based solely on location seems inappropriate. The categories of benign or malignant are more realistic. Benign lesions may then be subdivided into aggressive and nonaggressive. Multifocal giant cell lesions strongly suggest the brown tumor of hyperparathyroidism. Serum chemistry tests including calcium, phosphorus, ionized calcium, and PTH levels should routinely be obtained when a giant cell lesion is suspected. A case of benign, aggressive, multifocal central giant cell lesions of the maxillofacial skeleton, in the absence of either primary or secondary hyperparathyroidism is presented. Whether this represents metastasis from the initial lesion, metabolic osteoclastic dysfunction, or a new entity, craniofacial giant cell dysplasia, is unknown

An experimental study evaluating the contributions of graft composition (particulate vs. whole) and revascularization (immediate reanastomosis vs. delayed) to cervicofacial fat transplantation was conducted in rats. Distant (inguinal fat) grafts were bilaterally transplanted to a muscular bed in the cervicofacial region as a free flap (anastomosis to carotid and jugular vessels) or as a free graft (either particulate or whole). Postoperative assessment was made by comparison of pre- and post-operative weights and histologic examination of all specimens, and by acrylic microangiography in select animals of each group. The fat flaps exhibited minimal loss of tissue volume, and showed a normal histologic appearance of the adipocytes and extensive vascular elements within the grafts. Conversely, considerable volume loss occurred in both the particulate and whole fat grafts. Histologically, the free graft was characterized by cellular disruption, atrophic adipocytes, and areas of acellularity. Whole grafts had histologic evidence of vessels located primarily at the periphery, whereas particulate grafts had increased intragraft vessels. Only the fat flaps showed observable intragraft vasculature by microangiography. These findings suggest that reduction of fat grafts into smaller components, eg, by liposuction harvesting, does not improve graft survival or decrease posttransplant resorption

A study was designed to evaluate the effects of different types of repair (suture vs. graft), donor graft tissues (dermis vs. fascia), and methods of graft fixation (sutured vs. laser-assisted) on excisional defects of the rabbit TMJ disc made anterior to the retrodiscal tissue. Groups created to compare the different variables were assessed at 30 and 90 days postoperatively by macroscopic and histologic methods, microangiography, and mechanical strength testing. Without repair, all excisional defects of the disc failed to heal. Suturing of the reapproximated margins did not appear to promote healing or provide much strength beyond the properties of the suture material. Dermal grafts, fixed by suturing, induced healing by becoming incorporated into the disc, restoring discal continuity, and approximating normal disc strength. The use of laser-assisted tissue welding for dermal graft fixation was found to be inadequate and was subsequently abandoned. Fascial grafts could be fixed into position by both suture and laser-assistance, but consistently failed to exhibit successful transplantation and promote healing at the disc site

A study was designed to evaluate the ability of the rabbit mandibular nerve to regenerate when exposed to crush and resection injuries, as well as to determine how differently sized resection injuries healed when repaired with either autogenous grafts or laminin-lined collagen tubulization. The nerve demonstrated a regenerative capacity over a 1-cm defect, with morphology and function that approximated normals, but could not span a 2-cm gap defect unaided. Crush injuries produced findings that were inferior to both those in normal nerves and in those with resections. In 1-cm defects, both grafting and tubular repairs produced similar results, with substantial recovery of neural function after 16 weeks. In 2-cm defects, autogenous grafting was superior to tubulization by both morphologic and functional assessment. Replacement of the lateral cortex of the mandible after nerve repair was shown to be unnecessary. The implications of these findings as they relate to nerve injury and repair in humans is discussed

An experimental study was conducted to evaluate the effectiveness of laser-assisted versus conventional suture repair of facial nerve grafts in the rabbit. Electrophysiologic assessment of function revealed no significant difference between the two techniques. Histological differences were apparent, however, early postoperatively from the effects of heat energy on the perimeter of fascicular morphology. At a later stage, this effect had disappeared. The laser technique was also associated with an apparent decreased escape and entrapment of axons

An unusual case involving the development of patency of the nasopalatine ducts after orthopedic expansion of the premaxilla in a young child is described. The embryogenesis, clinical presentation and surgical repair is discussed