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Biomedical subjects

J F Reuther

Publications and source records attributed to J F Reuther.

At least 19 recordsLinked to original sources

[Rapid prototyping in planning reconstructive surgery of the head and neck. Review and evaluation of indications in clinical use].

PURPOSE: The aim was to define the indications for use of rapid prototyping models based on data of patients treated with this technique. PATIENTS AND METHODS: Since 1987 our department has been developing methods of rapid prototyping in surgery planning. During the study, first the statistical and reproducible anatomical precision of rapid prototyping models was determined on pig skull measurements depending on CT parameters and method of rapid prototyping. RESULTS: Measurements on stereolithography models and on selective laser sintered models confirmed an accuracy of +/-0.88 mm or 2.7% (maximum deviation: -3.0 mm to +3.2 mm) independently from CT parameters or method of rapid prototyping, respectively. With the same precision of models multilayer helical CT with a higher rate is the preferable method of data acquisition compared to conventional helical CT. From 1990 to 2002 in atotal of 122 patients, 127 rapid prototyping models were manufactured: in 112 patients stereolithography models, in 2 patients an additional stereolithography model, in 2 patients an additional selective laser sinter model, in 1 patient an additional milled model, and in 10 patients just a selective laser sinter model. CONCLUSION: Reconstructive surgery, distraction osteogenesis including midface distraction, and dental implantology are proven to be the major indications for rapid prototyping as confirmed in a review of the literature. Surgery planning on rapid prototyping models should only be used in individual cases due to radiation dose and high costs. Routine use of this technique only seems to be indicated in skull reconstruction and distraction osteogenesis.

Computer Graphics↗

[Mandibular reconstruction with autologous bone and osseoinductive implant in the Göttingen minipig].

BACKGROUND: Direct mandibular reconstruction with an autologous bone transplant was compared with an osteoinductive implant following an extensive continuity resection of the lower jaw in Göttinger mini-pigs. METHOD: In nine full-grown mini-pigs a one-sided continuity defect (5 cm) was created in the lower jaw. In four animals it was filled with a 50 x 25 x 15 mm(3) collagenous carrier enhanced by rhBMP-2 (400 micro g/cm(3) rhBMP-2). In two animals only the carrier was implanted as a control. Three animals received the resected autologous bone as a free transplant. Bone regeneration and consolidation of the defects was analyzed radiographically and histologically. RESULTS: Following implantation of the osteoinductive implant, complete osseous consolidation of the continuity defect in the lower jaw was observed in all animals. The defects were completely filled with a biomechanically stable bone which showed signs of functional adaptation. The replantation of the orthotopic autologous bone did not lead to functional stability quickly enough. In the periphery only an incomplete bony bridge was formed which was interrupted by large pseudarthrosis. No consolidation of the defects was found in the control group (carrier alone). CONCLUSION: Direct reconstruction of an extensive, biomechanically loaded defect with an osteoinductive implant proved to be the superior method. The osseous regeneration observed shows an immediate functional orientation. The necessity for extensive adaptive remodeling is thus minimized.

Animals↗

[Evaluation of the osteoinductive potential of genetically modified BMP-2 variants].

BACKGROUND: The alteration of the N-terminal amino acid sequence of BMP-2 allows modification of heparin binding of the new protein. This leads to a change in the local retention time at the site of implantation. Mutants with increased (T3, T4) and with no binding (EHBMP-2) to heparin were assessed for their osteoinductivity in vivo and compared with the wild type BMP-2. METHODS: Cylindrical collagenous carriers (diameter = 5 mm, height = 10) were loaded with different concentrations (0.25-4 micro g) of the proteins. Following intramuscular implantation into the hind legs, the bone formation was measured in radiographic follow-ups. After 28 days the newly formed bone was characterized histologically. RESULTS: Elimination of the heparin binding leads to massive reduction in osteoinductivity. On the other hand, an increase in the heparin binding leads to enhancement in the osteoinductive properties, resulting in faster bone formation with a higher yield. CONCLUSION: It could be shown for the first time that modifications of BMP-2 by gene technology can lead to proteins with enhanced binding to components of the extracellular matrix. The resulting prolonged retention time at the implantation site results in an increased osteoinductivity compared with the wild type.

Amino Acid Sequence↗

[Bimaxillary osteotomy with and without condylar positioning--a 1981-2002 long-term study].

PURPOSE: The introduction of the four-splint technique in our hospital in 1997 made possible the reproducible centric condyle positioning in bimaxillary osteotomies, while taking the auto rotation of the mandible into consideration and avoiding steps in the mandibular osteotomy line. PATIENTS AND METHODS: From 1981 to 2002 a total of 622 patients underwent bimaxillary osteotomy surgery. During 1981-1997 a total of 395 patients (63.5%) underwent surgery without or only with centric condyle positioning in sagittal ramus osteotomy of the mandible. During 1997-2002 a total of 227 patients (36.5%) underwent surgery with continuous centric condyle positioning with the four-splint technique. RESULTS: In patients with preoperative functional disorders, surgery with continuous centric condyle positioning resulted in statistically significant (p<0.05) improvement compared to those who underwent surgery without continuous centric condyle positioning. CONCLUSION: The results confirm the indication for continuous centric condyle positioning in bimaxillary osteotomies.

Dental Occlusion, Centric↗

[Effect of periosteum on induced bone formation by autolyzed, antigen-extracted, allogeneic bone. Determination of the extent of bone formation using quantitative computerized tomography].

Autolyzed, antigen-extracted, allogenic (AAA) bone is an osteoinductive preparation of completely demineralized bone matrix. It has been clinically applied for years. In an experimental study in rabbits, we evaluated the influence of cortical bone and periosteum on the amount of bone formation following augmentation with AAA bone. Two implants of standardized size were placed on the femoral bone of rabbits. A cell-excluding PTFE membrane was wrapped circularly around the femur as well as the anterior implant shielding the implant from the surrounding periosteum. The posterior implant was exposed directly to the periosteum while being shielded from the cortical bone by the membrane. Thus, two compartments were created selectively, preventing contact between the periosteum or cortical bone and the implants. For each compartment the area and volume of the induced new bone were evaluated by computerized radiograph analysis and quantitative CT (pQCT) scans. Implantation of AAA bone led to new bone formation in both compartments. Contact of the periosteum and the implant led to an almost four-fold increase in bone volume. Although bone formation showed interindividual variations, the difference of both compartments was highly significant using the Student's t-test for paired samples (P < 0.0001). The data show that periosteum is the primary source of new bone formation in augmentations with osteoinductive materials as it is rich in inducible progenitor cells and is well vascularized. In osseous augmentations with AAA bone, the periosteum should be preserved in order to achieve a close contact of the osteoinductive implant. Shielding from the periosteum, e.g., by cell-excluding membranes, leads to significantly less bone formation following implantation of AAA bone and should therefore be avoided.

Animals↗

[Effect of different factors on the bone forming properties of recombinant BMPs].

The extent of BMP-induced new bone formation is mainly determined by the number of mesenchymal target cells in the recipient bed as well as by the biological half-life of the BMP molecules within the tissue. While the number of inducible cells is determined by the age and vascularization of the tissue, the retention time of the BMP molecules can be influenced. One possibility is the coupling of BMPs to suitable carriers, which significantly increases the osteoinductive effect. The reason for this is the physical binding of BMPs to the carrier material, which delays the resorption of the proteins. Other factors are the composition of the carrier materials, their structural stability, and possible dislocations of carrier particles. The local tissue concentration of BMPs can also be increased by an enhanced binding of the proteins to the extracellular matrix. A BMP-2 mutant (BMP-2xa) was produced by the specific modification of the amino acid sequence using recombinant technologies. BMP-2xa induces heterotopic bone formation at significantly lower concentrations than natural BMP-2. Furthermore, BMP-2xa-induced bone tissue possesses a higher bone density.

Animals↗

[EHBMP-2. Initial BMP analog with osteoinductive properties].

For the first time a non natural BMP-variant (EHBMP-2) with osteoinductive properties was produced by expression in E. coli through specific mutation of the amino acid sequence. The substitution of 12 N-terminal amino acids by a nonsense sequence results in a neglectible affinity of EHBMP-2 to the extracellular matrix. In vitro EHBMP-2 induces dose-dependent cartilage formation in neonatal muscle tissue. Single intramuscular implantation in mice results in the formation of an ossicle with functional active bone marrow. The size of the ossicle depends on the amount of implanted EHBMP-2 and can significantly be increased by the combination with a collagen carrier. The largest bone formation is observed after injection of EHBMP-2 containing collagen suspensions. In rats a stronger osteoinductive activity can be achieved by coupling of EHBMP-2 to collagen discs than by coupling natural BMP-2 to the same collagen carrier. Critical size defects in rats' mandibular angels can be restored by the combination of granular collagenous bone matrix (ICBM) with EHBMP-2. Further investigations have to show whether the altered pharmacokinetics of EHBMP-2 has advantages regarding its therapeutical use and tissue-engineering.

Amino Acid Substitution↗

[Comparative studies of sinus floor elevation with autologous or allogeneic bone tissue].

In 63 patients, 82 elevations of the maxillary sinus were performed. As augmentation, materials autografts from the iliac crest (combined with alveolar ridge augmentations in 16 sinus lifts) were transplanted in 39 cases and osteoinductive, allogeneic bone powder (AAA bone (autolyzed, antigen-extracted, allogeneic bone): n = 8, DFDBA (demineralized freeze-dried bone allograft) and/or Grafton (demineralized bone matrix gel): n = 35) were used in 43 cases. Some 4-6 months after implantation, osteoinductive, allogeneic (demineralized) bone implants showed radio-opaque areas as an equivalent of bone formation. Histological examinations revealed that osteoinductive implants were completely transformed into patients' own bone tissue. The average augmentation height after autograft transplantations was 14 (+/- 3) mm in comparison with 9 (+/- 3) mm after allograft implantations. Histologically as well as radiologically no differences of the bone quality could be determined between the two augmentation materials. Endoscopic controls showed, in both groups, nonirritated mucous membranes. On an average 2 endosseous implants (Bone Lock or ITI-screw implants) were inserted into the augmentated maxillary sinus floors in both groups. No osseointegration was achieved in 4 out of 67 dental implants when bone autografts were used and in 2 out of 74 dental implants of the allogeneic bone group. Patients with bone autografts suffered from postoperative complaints on an average of 19 (+/- 9) days (without consideration of 2 patients with postoperative complaints persisting for more than 90 days). The average postoperative complaints of recipients of allogeneic bone implants continued for 3 (+/- 5) days. The 13 patients who underwent an ambulant sinus lift procedure with allogeneic bone powder were already symptom-free several hours after the operation. Under critical consideration of all investigated parameters, osteoinductive bone implants are preferable to iliac bone autografts for maxillary sinus augmentations in those cases in which no additional alveolar ridge augmentation is required.

Alveolar Bone Loss↗

[Biological activity of E. coli expressed BMP-4].

BMP-4 is physiologically present in low concentrations in human bone matrix. So far the protein has only been produced in small quantities by expression in mammalian cell cultures. In this study we investigated the biological activity of E. coli-expressed BMP-4. In vitro neonatal rat muscle tissue was incubated together with BMP-4 during 4 h, followed by an incubation period of 14 days on cellulose acetate membranes in BMP-free medium. The addition of 0.4 microgram BMP-4 induced cartilage formation in 1/8 samples while 4 micrograms BMP-4 showed chondroneogenesis in 2/10 samples. When the BMP-4 concentration was increased to 40 micrograms, new cartilage formation was seen in 5/7 samples. In vivo BMP-4 was implanted intramuscularly for 3 weeks in ICR mice. Amounts of 10 micrograms rhBMP-4 and more (up to 100 micrograms) constantly induced heterotopic ossicle formation. BMP-4 was also combined with a collagen carrier and implanted for 2 and 4 weeks in the abdominal muscle of SD rats. While 0.4 microgram BMP-4 showed no bone or cartilage formation, the amount of 40 micrograms BMP-4 showed new heterotopic cartilage formation, followed by endochondral ossification in almost all samples. The results prove that E. coli-expressed BMP-4 possesses the same inductive properties as mammalian-cell-expressed BMP-4.

Animals↗

[Clinical application of osteoinductive implants in craniofacial surgery].

Autolyzed, antigen-extracted, allogeneic bone (AAA bone) is prepared from cortical bones of human organ donors. AAA bone possesses osteoinductive properties as it delivers BMPs from its bone matrix. Within a prospective study, 37 cranial defects were reconstructed using AAA bone implants over a period of more than 7 years. The patients were followed-up at standardized intervals. Roentgenographic assessments and bone scintigraphies revealed osseous integration and remodelling of the AAA bone implants. In one quarter of the cases re-entry was performed 10 to 18 months after the cranioplasty (removal of osteosynthesis material, recurrence of tumor). All nine AAA bone reconstructions showed bleeding surfaces and bony integrations. A bone biopsy was taken from the center of one of these AAA bone implants and this showed new bone formation originating from the surface of the implant. In one case an AAA bone implant was lost due to infection. This is noteworthy as in approximately one third of the cases the bone implants were in direct contact with the frontal sinus. The clinical results clearly emphasize the therapeutical benefit of AAA bone for cranioplasties. Large AAA bone chips from human skull bones facilitate the reconstruction of the skull's convexity, especially when sterolithography-based operation planning is performed.

Adolescent↗

Inductive properties of recombinant human BMP-2 produced in a bacterial expression system.

Recombinant human BMP-2, produced in E. coli, refolded and concentrated to a purity of more than 98%, has been demonstrated to be biologically active. In vitro, amounts of 0.4 microg BMP-2 or more induced new cartilage formation in 27 out of 47 samples of a neonatal muscle tissue assay, with chondroneogenesis occurring 14 days after a four-hour contact between BMP-2 and the muscle tissue. In vivo, BMP-2 was implanted in the thigh muscle of ICR mice for a period of three weeks. Amounts of 4 microg BMP-2 and more showed heterotopic bone formation in 15 out of 17 samples. When BMP-2 was combined with a collagen carrier, amounts of 0.4 microg protein or more induced heterotopic bone formation in 30 out of 33 samples four weeks after the implantation in the abdominal wall of Sprague-Dawley rats. The results show that the E. coli-derived BMP-2 was active in different assay systems in concentrations equal to those required with mammalian cell-expressed BMP-2. It could also be demonstrated that a single morphogen (BMP-2) is enough to initiate the differentiation process associated with bone induction. The presented bacterial expression system also offers the opportunity to produce large quantities of recombinant BMP-2 for clinical applications.

Abdominal Muscles↗

Long-term maintenance of alveolar bone gain after implantation of autolyzed, antigen-extracted, allogenic bone in periodontal intraosseous defects.

This randomized controlled trial assessed the long-term maintenance of alveolar bone gain after implantation of autolyzed, antigen-extracted, allogenic (AAA) bone. AAA bone is a demineralized freeze-dried bone allograft processed after previously described methods. In each of 14 patients, AAA bone was implanted into the intraosseous defect of 1 tooth (test); a second tooth with an intraosseous defect was treated by modified Widman flap surgery alone (control). All patients were offered supportive periodontal therapy at 3- to 6-month intervals following treatment. Clinical measurements were taken prior to surgery, 6 months, and 3 years following surgery. Of the 14 patients enrolled, 11 patients completed the 6-month and 8 patients the 3-year examination. In test teeth, bone gain was significantly greater compared to control teeth at 6 months (2.2+/-0.5 mm and 1.2+/-0.5 mm, respectively) and 3 years (2.3+/-0.7 mm and 1.1+/-0.8 mm, respectively) (P < 0.05). Also, more probing attachment was gained in test compared to control teeth at 3 years (2.0+/-0.7 mm and 0.8+/-0.5 mm, respectively; P < 0.05). At 3 years, Porphyromonas gingivalis was detected in 3 test and 2 control teeth by polymerase chain reaction, whereas no Actinobacillus actinomycetemcomitans was found. Due to the low detection frequency, there was no clear correlation between the maintenance of alveolar bone during supportive periodontal therapy and subgingival infection with P. gingivalis. The data indicated that alveolar bone gain after implantation of AAA bone may be maintained over a minimum of 3 years in patients receiving periodontal supportive therapy.

Adult↗

[Osteosynthesis after sagittal division of the mandible. Biomechanical stability of various methods in a pig mandibular model].

Forty years after the introduction of sagittal split osteotomy for transposition of the mandible according to Obwegeser, very different procedures for osteosynthesis are still discussed and practised. In a simple biomechanical model in the porcine mandible, five different methods for osteosynthesis using metallic screws (titanium, cobalt-chromium-molybdenum alloy) and one using a polymer screw (polylactic acid-copolymer blend), as well as the use of miniplates, were studied with regard to the stability of the compound. The Kruskal-Wallis H-test (variance analysis by ranks) showed statistically highly significant differences (P = 0.00017) regarding maximum stability. Osteosynthesis by miniplates was very stable with regard to the maximum load (Fmax = 234 N +/- 47), but not so in terms of three-dimensional stability of the osteosynthesis itself. The highest stability of osteosynthesis with screws only (Fmax = 183 N +/- 65) was found for a 2.7-mm titanium screw in triangular geometry. The use of 2.7-mm cobalt-chromium-molybdenum screws (Fmax = 173 N +/- 42) and 3.5-mm titanium screws (Fmax = 160 N +/- 76) did not make an statistical difference (P = 0.37). The mechanical values of 2.0-mm titanium screws in linear (Fmax = 113 N +/- 37) or triangular (Fmax = 136 N +/- 62) geometry and of 3.5-mm polylactic acid-copolymer blend screws (Fmax = 121 N +/- 33) did not differ statistically from each other (P = 0.75) but they did from the previous group (P = 0.019). In consideration of the low biting forces following sagittal split osteotomy, all tested procedures of osteosynthesis meet the mechanical requirements for clinical practice.

Animals↗

[Interventions for improving the facial profile with osteoinductive bone implants].

Osteoinductive bone allografts (autolyzed, antigen-extracted, allogeneic bone; AAA bone) were implanted in 207 cases. The patients had plastic surgery procedures to improve their profiles and were followed up for a maximum of 72 months. Twenty-two patients had an asymmetric mandible corrected with AAA bone chips. In 14 cases AAA bone implants were used for genioplasties. Forehead defects were reconstructed in 20 patients using AAA bone. Hypoplasia of the midface was corrected in 88 cases by augmentations with AAA bone chips or powder. A total of 63 patients underwent rhinoplasties in which AAA bone chips were used to shape or erect the dorsum nasi. Patient follow-up and reoperations to remove the osteosynthesis material revealed that the AAA bone implants were remodeled in the patients' own bone within several months. Less than 3% of the AAA bone implants were lost due to local infections. Except for rhinoplasties, secondary resorption of the bone allografts was extremely low. However, in cases in which strong tension resulted from scar formation or from lack of soft tissue, considerable resorption was observed, especially when AAA bone was implanted in the nose (25% of the rhinoplasties). On the other hand, this biodynamic behavior protected the implants from soft tissue perforation. In summary, AAA bone implants represent a convenient alternative to bone autografts in recipient beds with strong regenerative capacity. Since they are remodeled into the patient's bone none of the late complications found with alloplastic implants need to be expected.

Adolescent↗

[Therapeutic concept in comminuted and defect fractures of the mandible].

Immediate live-saving emergency treatment of patients with heavily communited and partially defective mandibles by airway intubation, control of haemorhage and primary treatment of wounds necessarily must be followed by a staged concept of treatment for the functional and aesthetic rehabilitation of hard and soft tissue in order to enable the patient to survive not only biologically but also socially. Out of 384 patients with surgically treated mandibular fractures, 120 had multiple fractures, 24 heavily comminuted fractures and 6 sustained vast defects. All multiple and communited fractures could be treated successfully by an intraoral approach using function-orientated miniplate-osteosynthesis and in 30 cases functionally stable plates. In patients having sustained vast avulsions of soft and hard tissue, immediate emergency-revascularisation was well to the fore. In cases of tissue destruction, primarily the position of the jaw stumps was secured by plates and reconstruction was done in the early secondary stage using composed microvascularly transferred scapular flaps.

Adult↗

Stereolithography in oral and maxillofacial operation planning.

Stereolithography (STL) is a method of organ-model-production based on computed tomography scans which enables the representation of complex 3-dimensional anatomical structures. Surfaces and internal structures of organs can be produced by polymerization of UV-sensitive liquid resin using a laserbeam. In oral and maxillofacial surgery this technique is advantageous for reconstruction of severe skull defects because a more accurate preoperative planning is possible. Using recently developed software we are able to reconstruct unilateral bony defects by virtual mirror imaging of the contralateral side and production of a STL mirror model as well as the reconstruction of non-mirrorable defects by superposition. Advantages of STL are the representation of complex anatomical structures, high precision and accuracy, and the option to sterilize the models for intraoperative use. More accurate planning using this method improves postoperative results, decreases risks and shortens treatment time.

Aged↗

[Microsurgical scapula transplants for reconstruction of the facial skull--experiences with 44 patients].

Great versatility gives composed scapular flaps a particular significance for the reconstruction of defects in face and skull: According to individual requirements one up to five separate elements may be transferred with one vascular pedicle. Anatomical studies of 120 scapulas measured a mean length of 13.4 cm and a mean diameter of 1.2 cm of the lateral margin offering sufficient bone for most indications in the visceral skull. Up to three cutaneous flaps may cover nearly every defect in the head. 44 patients were treated in the years 1989 to 1993 using scapular flaps, most of them combinations consisting of bone and skin elements. In two patients a so called 4-in-1-flap was transferred including the latissimus-dorsi-flap. All donor sites could be closed primarily. Venous thrombosis caused one loss of a flap. Infections healed without sequelae. Medical gymnastics brought full rehabilitation of the donor site within 6 months.

Bone Transplantation↗