Hendrik Terheyden

Mandibular reconstruction with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: an experimental study in miniature pigs. Part II: Transplantation

Osteogenic Protein-1 (rhOP-1), also called bone morphogenetic protein-7 (BMP-7), is osteoinductive. The aim of this study was to present a new surgical technique: the prefabrication of a vascularized bone graft using rhOP-1 and its microsurgical transplantation. During 6 weeks, osteomuscular grafts were prefabricated in the latissimus dorsi muscle of five adult minipigs. Six hundred micrograms rhOP-1 on a carrier of xenogenic bone mineral in block form were used. The grafts were transplanted into defects of the mandibular angles performing a microsurgical anastomosis and using miniplates for fixation. Identical defects of the contralateral side were treated by direct application of 600 microg rhOP-1 and xenogenic bone mineral. A polychrome sequential labelling was applied. After transplantation the bone stayed viable, demonstrated by continuous apposition of fluorochromes (non-decalcified histologic sections) and bone scintigraphy. The reconstructive result was significantly superior in the prefabrication technique, assessed by histology and computerized tomography (CT). In conclusion, the method has a potential to become a clinical alternative for conventional vascularized bone grafts.

Open reduction and internal fixation versus closed treatment and mandibulomaxillary fixation of fractures of the mandibular condylar process: a randomized, prospective, multicenter study with special evaluation of fracture level.

PURPOSE This randomized, clinical multicenter trial investigated the treatment outcomes of displaced condylar fractures, and whether radiographic fracture level was a prognostic factor in therapeutic decision-making between open reduction and internal fixation (ORIF) versus closed reduction and mandibulomaxillary fixation (CRMMF). PATIENTS AND METHODS Sixty-six patients with 79 displaced fractures (deviation of 10 degrees to 45 degrees, or shortening of the ascending ramus >or=2 mm) of the condylar process of the mandible at 7 clinical centers were enrolled. Patients were randomly allocated to CRMMF (n = 30 patients) or ORIF (n = 36 patients) treatment. The following parameters were measured 6 months after the trauma. Clinical parameters included mouth opening, protrusion, and laterotrusion. Radiographic parameters included level of the fracture, deviation of the fragment, and shortening of the ascending ramus. Subjective parameters included pain (according to a visual analogue scale), discomfort, and subjective functional impairment with a mandibular functional impairment questionnaire. RESULTS The difference in average mouth opening was 12 mm (P <or= .001) between both treatment groups. The average pain level (visual analogue scale from 0 to 100) was 25 after CRMMF, and 1 after ORIF (P <or= .001). In 53 unilateral fractures, better functional results were observed for ORIF compared with CRMMF, irrespective of fracture level (condylar base, neck, or intracapsular head). Unexpectedly, the subjective discomfort level decreased with ascending level of the fracture. In patients with bilateral condylar fractures, ORIF was especially advantageous. CONCLUSION Fractures with a deviation of 10 degrees to 45 degrees, or a shortening of the ascending ramus >or=2 mm, should be treated with ORIF, irrespective of level of the fracture.

Prospective observation of 41 perforations of the Schneiderian membrane during sinus floor elevation

OBJECTIVES The aim of this study was to follow 41 intraoperative perforations of the Schneiderian membrane during sinus floor elevation and to identify potential differences from patients without perforations. MATERIAL AND METHODS Two hundred and one sinus floor elevations were performed at the department of oral and maxillofacial surgery of the University Hospital of Schleswig-Holstein in the years 2005 and 2006. Forty-one intraoperative perforations (20.4%) were documented and treated according to the following scheme: defects smaller than 5 mm were covered with a collagen membrane. Larger defects were additionally sutured. Particulated jawbone mixed 50 : 50 with bone substitute (25 cases) and a 50 : 50 mix of particulated iliac crest bone and BioOss (six cases) mainly served as graft material in the perforation group. In 12 cases, implants were installed at the time of sinus grafting, and in 27 cases, a second operation was performed. RESULTS Four sinus lift procedures had to be discontinued intraoperatively. Over a mean control interval of 162 days, one implant of the 93 inserted had to be replaced in the perforation group. After 1 year, the implant survival rate was 14 out of 14 in the perforation group vs. 81/92 in the control group. CONCLUSIONS With appropriate treatment, intraoperative sinus membrane perforations did not represent an elevated risk for implant loss, infectious complications or displacement of graft material in the investigated population.

Maxillary sinus floor augmentation with Bio-Oss or Bio-Oss mixed with autogenous bone as graft: a systematic review.

AIMS The objective of the present systematic review was to test the hypothesis of no differences in the implant treatment outcome when Bio-Oss or Bio-Oss mixed with autogenous bone is used as graft for the maxillary sinus floor augmentation (MSFA) applying the lateral window technique. MATERIAL AND METHODS A MEDLINE (PubMed) search in combination with a hand search of relevant journals was conducted by including human studies published in English from January 1, 1990 to June 1, 2010. The search provided 879 titles and 35 studies fulfilled the inclusion criteria. Considerable variation in the included studies prevented meta-analysis from being performed and no long-term study comparing MSFA with the two treatment modalities was identified. Also, the survival of suprastructures after the two augmentation procedures was not compared within the same study. RESULTS The 1-year implant survival was compared in one study demonstrating no statistically significant difference. The implant survival was 96% with Bio-Oss and 94% with a mixture of 80% Bio-Oss and 20% autogenous mandibular bone. Addition of a limited amount of autogenous bone to Bio-Oss seemed not to increase the amount of new bone formation and bone-to-implant contact compared with Bio-Oss. CONCLUSIONS Therefore, the hypothesis of no differences between the use of Bio-Oss or Bio-Oss mixed with autogenous bone as graft for MSFA could neither be confirmed nor rejected.

Three-dimensional cultivation of human osteoblast-like cells on highly porous natural bone mineral.

In this study, we investigated the growth and extracellular matrix synthesis of human osteoblast-like cells on highly porous natural bone mineral. Human bone cells were isolated from trabecular bone during routine iliac crest biopsies. Under conventional culture conditions, trabecular bone cells were able to assume the organization of a three-dimensional structure on a porous natural bone mineral (Bio-Oss(R) Block). Scanning electron microscopy examination after 6 weeks revealed multiple cell layers on the trabecular block. Transmission electron microscopy examination after 6 weeks revealed the accumulation of mature collagen fibrils in the intracellular and extracellular spaces, and showed multilayered, rough endoplasmic reticulum as well as mitochondria-rich cells surrounded by dense extracellular matrix. These morphological observations suggest that the cell layer may resemble the natural three-dimensional structure. Biochemical analysis revealed that the hydroxylysylpyridinoline, lysylpyridinoline, and hydroxyproline content of the cell layer increased in a time-dependent manner, whereas in monolayer culture without natural bone mineral, no measurable amounts of hydroxylysylpyridinoline or lysylpyridinoline, and a barely measurable amount of hydroxyproline, were noted. Mature collagen extracted by ethylenediaminetetraacetic acid-demineralization from the cell layer on natural bone mineral showed an identical electrophoretic pattern to that observed in human bone, as evaluated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The present study demonstrated an excellent biocompatibility of the highly porous natural bone mineral in a three-dimensional bone cell culture system, and thus its potential for tissue-engineered growth of human bone.

Facial attractiveness: visual impact of symmetry increases significantly towards the midline.

Symmetry is thought to be a major prerequisite for an attractive face. Many faces are not symmetric, yet are still regarded as beautiful. What role, then, does asymmetry play in the perception of beauty? We studied the assessment of computer-manipulated images by independent judges (n = 200–250): part A: nevi located at different positions; part B: standardized changes of the orbital region. The results showed that slight lateral orbital and facial asymmetry does not impair attractiveness at all and that asymmetries close to the midline are significantly less attractive than those affecting the lateral aspect of the face (P < 0.001). A single nevus which is located laterally on the face is significantly more attractive than a nevus close to the midline (P < 0.001). Faces with a completely symmetric bilateral pair of nevi in the same lateral positions (perceived as attractive when alone), received the worst ratings (P < 0.001). Symmetry is a characteristic of the attractive face, but there are exceptions to the rule. Under certain conditions symmetry can be completely unattractive. The visual impact of symmetry on the perception of beauty increases significantly when approaching the midline.

Volumetric changes of the graft after maxillary sinus floor augmentation with Bio-Oss and autogenous bone in different ratios: a radiographic study in minipigs

OBJECTIVE The objective of the present study was to learn about the volumetric changes of the graft after maxillary sinus floor augmentation with Bio-Oss and autogenous bone from the iliac crest or the mandible in different ratios in minipigs. MATERIAL AND METHODS Bilateral maxillary sinus floor augmentation was performed in 40 minipigs with: (A) 100% autogenous bone, (B) 75% autogenous bone and 25% Bio-Oss, (C) 50% autogenous bone and 50% Bio-Oss, (D) 25% autogenous bone and 75% Bio-Oss, and (E) 100% Bio-Oss. The autogenous bone graft was harvested from the iliac crest or the mandible and the graft composition was selected at random and placed concomitant with implant placement. Computed tomographies of the maxillary sinuses were obtained preoperatively, immediately postoperatively, and at euthanasia after 12 weeks. The volumetric changes of the graft were estimated using the Cavalieri principle and expressed as mean percentage with a 95% confidence interval (CI). RESULTS The mean volume of the graft was reduced by (A) 65% (95% CI: 60-70%), (B) 38% (95% CI: 35-41%), (C) 23% (95% CI: 21-25%), (D) 16% (95% CI: 12-21%), and (E) 6% (95% CI: 4-8%). The volumetric reduction was significantly influenced by the ratio of Bio-Oss and autogenous bone (P<0.001), but not by the origin of the autogenous bone graft (P=0.2). CONCLUSIONS The volume of autogenous bone grafts from the iliac crest and the mandible is reduced significantly after maxillary sinus floor augmentation in minipigs. The graft volume is better preserved after the addition of Bio-Oss and the volumetric reduction is significantly influenced by the ratio of Bio-Oss and autogenous bone. However, further studies are needed addressing the amount of new bone formation and bone-to-implant contact before the final conclusion can be made about the optimal ratio of Bio-Oss and autogenous bone.

A comparison of biocompatibility and osseointegration of ceramic and titanium implants: an in vivo and in vitro study

This study compared the biocompatibility in vitro and the osseointegration in vivo of zirconium and titanium implants regarding implant surfaces and the bone-implant contacts. The different implant surfaces and the biocompatibility of zirconium versus titanium implants were determined by vitality and cytotoxic tests in vitro. The contact of the osteoblasts to the implant surface was determined by scanning electron microscopy (SEM). The in vivo study for osseointegration was performed in domestic pigs over 4 and 12 weeks. In each animal, 4 zirconium and 4 titanium implants (WhiteSky, BlueSky, Bredent, Germany) were inserted in the os frontale and analysed by histomorphometry. Cytotoxicity and SEM showed good biocompatibility in relation to the investigated implant materials. Histological results showed direct bone-implant contact of the implant surfaces. The zirconium implants showed a slight delay in osseointegration in terms of bone-implant contact as measured by histomorphometry (after 4 weeks, zirconium (59.3 ± 4.6%) versus titanium (64.1 ± 3.9%); after 12 weeks, zirconium (67.1 ± 2.3%) versus titanium (73.6 ± 3.2%). A statistically significant difference between the two groups was not observed. The results indicated similar biocompatibility and osseointegration for zirconium compared to titanium implants.

Use of a new cross-linked collagen membrane for the treatment of dehiscence-type defects at titanium implants: a prospective, randomized-controlled double-blinded clinical multicenter study.

OBJECTIVES The aim of the present randomized-controlled double-blinded clinical multicenter study was to assess the use of either a new cross-linked (VN) or a native collagen membrane (BG) for the treatment of dehiscence-type defects at titanium implants. MATERIAL AND METHODS A total of n=54 patients were recruited in four German university clinics. According to a parallel-groups design, dehiscence-type defects at titanium implants were filled with a natural bone mineral and randomly assigned to either VN or BG. Submerged sites were allowed to heal for 4 months. Primary (e.g., changes in defect length - DeltaDL, quality of newly formed tissue [0-4] - TQ) and secondary parameters (e.g., membrane exposure, tissue conditions at dehisced sites) were consecutively recorded. RESULTS Four patients were excluded due to an early wound infection (VN:3; BG:1), and one patient was lost during follow-up (VN). The mean DeltaDL was 3.0 +/- 2.5 mm in the VN, and 1.94 +/- 2.13 mm in the BG group. The assessment of TQ revealed comparable mean values in both groups (VN: 3.05 +/- 1.66, BG: 3.46 +/- 1.48). A significant correlation between membrane exposure and inflammation of the adjacent soft tissue was observed in the VN group. In both groups, the mean DL and TQ values were not significantly different at either non-exposed or exposed implant sites. CONCLUSION The results of the present study have indicated that VN supported bone regeneration on a level non-inferior to BG. However, in case of a premature membrane exposure, cross-linking might impair soft-tissue healing or may even cause wound infections.

Effects of bone morphogenetic protein‐7 stimulation on osteoblasts cultured on different biomaterials

The objective of the present study was to investigate the effects of an in vitro stimulation of human osteoblasts by recombinant human bone morphogenetic protein‐7 (rhBMP‐7) on the collagen types and the quantity of the collagen cross‐links synthesized in a three‐dimensional culture on various biomaterials for bone replacement. Trabecular bone chips were harvested from human iliac crests, and cell cultures were established at standard conditions. One hundred and fifty nanograms per milliliter of rhBMP‐7 was added. For the second passage a cell scraper was used to bring the cells into suspension, and 100 μl osteoblasts (at a density of 3.3 × 105) were transferred onto nine blocks of either Bio‐Oss®, Tutoplast®, or PepGen p‐15™. Blocks incubated with cells that were not treated with rhBMP‐7 served as controls. Cell colonization of the biomaterials was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) after a period of 2, 4, and 6 weeks. Throughout the experiment medium, supernatants were collected and collagen was characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). Finally, the collagen cross‐link residues hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were quantified by HPLC. Within 4 weeks the cells became confluent on all of the studied biomaterials. All samples synthesized bone specific LP and collagen type I. However, in rhBMP‐7‐stimulated samples, the amount of HP and LP found was increased by 45% compared to non‐stimulated samples. Cell proliferation and collagen synthesis was similar on the different biomaterials, but was consistently reduced in specimen not stimulated with rhBMP‐7. In vitro stimulation of osteoblasts on Bio‐Oss, Tutoplast, or PepGen p‐15 with rhBMP‐7 and subsequent transplantation of the constructs might lead to an enhanced osseointegration of the biomaterials in vivo. J. Cell. Biochem. 86: 90–98, 2002.