[Alternative bone replacement substances for preoperative design of individual CAD/CAM skull implants]. / Alternative Knochenersatzmaterialien zur präoperativen Fertigung individueller CAD/CAM-Schädelimplantate.

BACKGROUND: The preoperative manufacturing of individual skull implants using computer aided design (CAD) and computer aided manufacturing (CAM) is based on the use of titanium, although the use of other materials is also potentially possible. THE USE OF OTHER MATERIALS: The use of poly-(D,L-lactide) (PDLLA) as an implant material was investigated using an adult, formalin fixed sheep's head with a complex frontolateral defect. A standard individual titanium implant as well as a resection template made of aluminium were milled in order to allow bone resection and reconstruction within one operation. A mould was made of Teflon for the fabrication of the PDLLA implant using carbon dioxide at high pressure. This procedure allowed a critical comparison to be made of both implant materials and showed that the production of a biodegradable PDLLA implant is possible. At present the titanium implant is superior to the PDLLA implant, as PDLLA settled with slightly larger dimensions than the mould, although the structure itself was exact. DISCUSSION: The goal of the present research is the fabrication of a functionally graded material made of polylactide, polyglycolide, calcium phosphate and osteoinductive proteins using existing technology, which will meet all of the requirements for stability, resorption kinetics, biocompatibility, radiotranslucence and osteogenic potency of an ideal implant material.

Synthesis of CAD/CAM, robotics and biomaterial implant fabrication: single-step reconstruction in computer-aided frontotemporal bone resection.

The preoperative manufacturing of individual skull implants, developed by an interdisciplinary research group at Ruhr-University Bochum, is based on the use of titanium as the most common material for implants at present. Using the existing technology for materials that can be milled or moulded, customized implants may be manufactured as well. The goal of the study was to examine biodegradable materials and to evaluate the practicability of intraoperative instrument navigation and robotics. Data acquisition of an adult sheep's head was performed with helical computer tomography (CT). The data were transferred onto a computer aided design/computer aided manufacturing system (CAD/CAM system), and two complex defects in the frontotemporal skull were designed. Standard individual titanium implants were milled for both of the defects. Additionally, for one of the defects a resection template, as well as a mould for the biodegradable poly(D,L-lactide) (PDLLA) implant, were fabricated by the CAD/CAM system. A surgeon carried out the first bone resection (#1) for the prefabricated titanium implant using the resection template and an oscillating saw. The robot system Stäubli RX90CR, modified for clinical use, carried out the other resection (#2). Both titanium implants and the PDLLA implant were inserted in their respective defects to compare the precision of their fit. A critical comparison of both implant materials and both resection types shows that fabrication of a PDLLA implant and robot resection are already possible. At present, the titanium implant and resection using a template are more convincing due to the higher precision and practicability.

[Pilot study of controlled liberation of growth factors from polylactide implants]. / Pilotstudie zur kontrollierten Freisetzung von Wachstumsfaktoren aus Polylaktidkörpern.

The aim of the present study was to test polylactic acid material as a controlled release carrier for polypeptide growth factors. Basic fibroblast growth factor (bFGF) was incorporated into DL polylactic acid (PLA) pellets under hyperbaric CO2 pressure in two different ways. (1) Lyophilized bFGF was crushed and mixed with PLA granules, filled into cylindric moulds of 5 x 3 mm, and submitted to hyperbaric CO2 pressure. (2) Lyophilized bFGF was reconstituted in phosphate buffer, mixed with PLA granules, and relyophilized. In vitro assessment of bFGF release from the PLA implants by immunoassay showed that loading of PLA with crushed lyophilized bFGF resulted in a rapid and high release, while loading by solubilized bFGF and relyophilization led to a low and more regular release of the polypeptide growth factor.

Coronal suture response to distraction osteogenesis in rabbits with delayed-onset craniosynostosis.

Recent studies have identified a subpopulation of persons with craniosynostosis who exhibit progressive or delayed-onset synostosis and mild cranial vault deformities. These persons may be good candidates for nonextirpation distraction osteogenesis. The present studies were designed to determine force-displacement parameters and assess the effects of distraction osteogenesis on coronal suture growth and morphologic characteristics in a rabbit model with congenital, delayed-onset craniosynostosis. Data were collected from a total of 178 rabbits: 71 normal controls; 16 normal controls with distraction; 72 with delayed-onset coronal suture synostosis; and 19 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the coronal suture. In the force-displacement study, force-displacement distractors were placed across the coronal suture and distracted acutely for 1.0 mm at 42 days of age. Force-displacement curves for the coronal suture were best described by a third-order polynomial regression equation for both normal and synostosed groups. Significant differences (P < 0.05) were found in the mean force necessary to distract a normal suture 1 mm in distance (13.72 kg) compared with a suture with delayed-onset synostosis (48.39 kg). A significant (P < 0.05) relationship was also found between the extent of synostosis and the distractive force in rabbits with delayed-onset synostosis. In the distraction study, internal distractors were fixed across the coronal suture at 25 days of age and percutaneously and intermittently activated at an average of 0.11 mm/day for 42 days (4.54 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis and distraction had significantly (P < 0.01) more coronal suture growth rates compared with rabbits with delayed-onset synostosis and no distraction. Coronal sutures were harvested at 84 days of age for qualitative histologic examination. Normal, distracted coronal sutures showed widened sutural ligaments and thin, active osteogenic fronts. In contrast, distracted coronal sutures from rabbits with delayed-onset synostosis showed narrowed sutural ligaments, thickened and blunt osteogenic fronts, and increased collagen and bony matrix deposition compared with controls. Results suggest that distraction osteogenesis without corticotomy may be a treatment alternative in persons with progressive, delayed-onset synostosis. However, these preliminary data also suggest that distractive forces may accelerate or stimulate osteogenesis differentially in persons with craniosynostosis, possibly through an underlying genetic disorder of bone and cytokine regulation. These differential osteogenic responses to distraction, if validated clinically, will need to be taken into account when planning distraction rate and rhythm protocols for patients with craniosynostosis.

Internal calvarial bone distraction in rabbits with delayed-onset coronal suture synostosis.

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.

Internal calvarial bone distraction in rabbits with experimental coronal suture immobilization: effects of overdistraction.

This study was designed to assess the effects of overdistraction of an experimentally immobilized coronal suture using an internal appliance on craniofacial growth in rabbits. Fifty-three, 1.5-week-old rabbits were used. Markers were placed on either side of the calvarial sutures. Thirty-nine rabbits had bilateral coronal suture immobilization using methyl methacrylate; 14 rabbits served as normal controls. At 6 weeks of age, the 39 immobilized rabbits were randomly assigned to four groups: (1) immobilized controls (n = 14); (2) suturectomy (n = 6); (3) suturectomy with distraction (n = 9); and (4) suturectomy with overdistraction (n = 10). Lateral head radiographs were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that, by 18 weeks of age, rabbits with overdistraction exhibited significant compensatory growth abnormalities in the cranial vault, midface, and anterior cranial base compared with the other groups. Results indicate that overdistraction may contribute to craniofacial anomalies through altered growth vectors and compressive tension-stress forces at adjacent sutures and suggest that it may be important to keep "pace" with the growing coronal suture and neurocapsular matrix during distraction to reestablish normal craniofacial morphology.

Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of implantation.

A recently developed biodegradable system made of DL-polylactic acid (DL-PLA) for internal fixation of non-weight-bearing bones of the craniofacial skeleton was investigated. The plates were used for rigid fixation of experimental nasal bone fractures in 20 New Zealand white rabbits. In addition, prebent plates were placed in subcutaneous pockets in the backs of the animals. The material was removed after 7, 14, 28, and 42 days, and bending angles, plate stability, molecular weights (MW), and histologic analyses were studied. A significant decrease of MW over time and a difference in MW loss, showing a faster degradation subcutaneously, were observed. Plate stability did not decrease during the interval of 6 weeks, but a loss of bending angle was found in all prebent implants. This effect was caused by memory of DL-PLA. The results suggest that memory of biodegradable materials should be investigated before clinical application and that degradation rates differ according to the site of implantation.

Internal calvarial bone distraction in rabbits with experimental coronal suture immobilization.

Correction of craniosynostosis involves removal of the coronal suture to allow for expansion of the developing brain and normal craniofacial growth. Frequently, however, the site reossifies, restricts growth, and requires additional surgery. The present study was designed to assess the effects of an internal, subperiosteal calvarial distractor on suturectomy site patency and compensatory craniofacial growth changes in an experimental rabbit model of coronal suture synostosis. In the present study, 43 1 1/2-week-old rabbits were used. Amalgam markers were placed across the frontonasal, coronal, and anterior lambdoidal sutures in all animals. Twenty-nine rabbits underwent bilateral coronal suture immobilization using methyl methacrylate. Fourteen rabbits were left untreated and served as sham controls. At 6 weeks of age, the immobilized rabbits were divided into three groups: (1) immobilized (controls), (2) suturectomy, and (3) suturectomy and distraction. The distractors were activated percutaneously at an average of 0.6 mm/week for 5 weeks (3 mm total). Lateral head radiographs were taken at 1 1/2, 6, 12, and 18 weeks of age. Results revealed that, by 6 weeks of age, animals with coronal suture immobilization exhibited significantly (p < 0.01) reduced growth across the coronal suture, resulting in shorter and inferiorly rotated cranial vaults compared with sham controls. By 12 weeks of age, rabbits with distraction returned to normal (sham control) coronal suture marker separation, whereas rabbits with immobilized sutures and suturectomy only showed significantly reduced marker distances. Rabbits with distraction also exhibited greater anterior cranial base lengths compared with the other experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Teratogenic effects in a case of maternal treatment for acute myelocytic leukaemia--neonatal and infantile course.

Experience with the use of cytotoxic drugs in the first trimester of pregnancy is limited. We report on the clinical phenotype and infantile development of a girl born to a 36-year-old mother. Before recognition of pregnancy, the latter had been treated for acute myelocytic leukaemia receiving cytarabine, daunorubicin and doxorubicin at conception and cytarabine and thioguanine at about 35-37 days post conception. At delivery, there were severe brachycephaly, hypoplasia of the anterior cranial base and the midface as well as synostoses of both coronal and metopic sutures. Further findings included bilateral four-finger hands with hypoplastic thumbs and absent radii. This phenotype is reminiscent of the Baller-Gerold syndrome. The child, at present 15 months old, has had to undergo two operations for fronto-orbital advancement because of insufficient growth of the mid-face, nasal airway hypoplasia and increased intracranial pressure. Motor milestones are slightly retarded--neurodevelopment is otherwise normal. These findings are discussed in the context of the few previous reports and are particularly important for future genetic counselling.

Memory of DL-polylactic acid biodegradable plates.

Biodegradable plates and screws have many advantages over metal plates and screws. Plates were injection-molded and made of DL-polylactic acid. Four-hole plates were bent with the use of a heated tip to angles of 30, 45, and 60 degrees. They were inserted in the subcutaneous space in the back of rabbits. After 2 weeks, the plates straightened, suggesting that the plates had a memory. The results were confirmed by similar in vitro investigations. The in vitro experiment was repeated with tempering of the plates. The plates were heated to a temperature of 200 degrees C for 45 seconds, cooled, and then again heated to 200 degrees C for 40 seconds. This process resulted in loss of memory of the plates. After 4 weeks, there was a change of the bending angle of less than 2.5 degrees.

Experimental studies of DL-polylactic acid biodegradable plates and screws in rabbits: computed tomography and molecular weight loss.

A series of studies were designed to assess the potential of biodegradable DL-polylactic acid (DL-PLA) plates and screws for use in craniofacial surgery. We report on computed tomography (CT) scanning for visualization and postoperative follow-up and the short-term degradation sequelae of a biodegradable plate and screw system in an experimental animal model. Fractures of the nasal bones were created in 20 adult New Zealand white rabbits and rigidly fixed bilaterally with 4-hole plates and screws (n = 12), or left unrepaired for control data (n = 8). CT density, molecular weight, loss of plates and screws, and preliminary bone healing were assessed at 1, 2, 4, and 6 weeks postoperatively. Histologically, no differences in bone healing were noted between control and experimental animals at any time. Three-dimensional CT reconstruction of the skull was possible without artifacts, and no significant differences (p > 0.05) were found in specific CT scan density levels across postoperative intervals. However, significant (p < 0.001) molecular weight loss of the biodegradable plates was observed through 6 weeks postoperatively, reaching approximately 50% of the preoperative molecular weight. Molecular weight loss, however, was not detectable with CT density measurements. Results demonstrated that the use of biodegradable DL-PLA plates and screws had no adverse effect on fracture healing in this model and that CT scanning and three-dimensional reconstruction were possible without artifacts, independent of material degradation and molecular weight loss. These results suggest that this DL-PLA biodegradable system may have the potential for use in craniomandibulofacial surgery when short-term rigid fixation is necessary.

Congenital bilateral coronal suture synostosis in a rabbit and craniofacial growth comparisons with experimental models.

Experimental rabbit models of postnatal coronal suture (CS) synostosis have helped make significant contributions towards the understanding and surgical management of human congenital craniosynostosis. The present study compares craniofacial growth patterns in animals with experimental CS immobilization and in a rabbit born in our laboratory with congenital CS synostosis. The study sample consisted of 10 sham controls, 14 experimental animals with bilateral CS immobilization, and one animal with congenital, bilateral CS synostosis. At 1.5 weeks of age, all animals had amalgam markers placed on either side of the frontonasal, coronal, and anterior lambdoid sutures. At this time, the experimental animals had bilateral CS immobilization using methyl-methacrylate. Serial lateral head x-rays were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that by 1.5 weeks of age the congenital animal already exhibited changes in the cranial vault, cranial base, midface, and orthocephalic cranial base angles compared to controls. By 6 weeks of age, animals with experimental immobilization showed compensatory growth patterns similar to the congenital animal, particularly at the calvarial sutures and upper midface. This pattern continued through 18 weeks. Results showed that experimental, postnatal CS immobilization produced similar craniofacial growth patterns to those observed for our single congenital animal, but to a lesser degree, and therefore validates, in part, findings from experimental rabbit models of synostosis.

The buccal mucosal graft for urethral reconstruction: a preliminary report.

Autologous buccal mucosa as a substitute for urethral epithelium was studied in 2 dogs and used in 6 patients with difficult urethral reconstruction problems. The indications for an operation in these patients were failed hypospadias repairs with limited skin in 3, severe structure disease after hypospadias repair in 1, a short urethra in 1 and epispadias in 1. Three urethral fistulas and 1 meatal stenosis occurred in 3 patients. No urethral stricture or diverticulum was noted, and the final outcome was good functionally and cosmetically in all patients. This technique is useful for urethral reconstruction when local skin is not available.

[Acute necrotizing bone destruction of the maxillary and mandibular midline area in HIV infection cases]. / Akute nekrotisierende Kieferdestruktion im Ober- und Unterkiefermittellinienbereich bei HIV-Infektion.

An HIV positive patient with extensive destructions in the midline area of maxilla and mandible is presented. The diagnosis had to differentiate between rapidly progressing periodontitis, lethal midline granuloma, specific inflammation, and tumors. Course of the disease and histological workup led to the diagnosis of rapidly progressing periodontitis. The relationship between midline granuloma and immune deficiency should be noted.