Friedrich Wilhelm Neukam

TiO2 Nanotube Surfaces: 15 nm—An Optimal Length Scale of Surface Topography for Cell Adhesion and Differentiation†

Studies of biomimetic surfaces in medicine and biomaterial fields have explored extensively how the micrometer-scale topography of a surface controls cell behavior, but only recently has the nanoscale environment received attention as a critical factor for cell behavior. Several investigations of cell interactions have been performed using surface protrusion topographies at the nanoscale; such topographies are typically based on polymer demixing, ordered gold cluster arrays, or islands of adhesive ligands at distinct length scales. Recent work has indicated that the fabrication of ordered TiO2 nanotube layers with controlled diameters can be achieved by anodization of titanium in adequate electrolytes. Such surfaces can almost ideally be used as nanoscale spacing models for size-dependent cellular response. This is particularly important as these studies are carried out on titanium surfaces—a material used for clinical titanium implantations for the purpose of bone, joint, or tooth replacements. Therefore, principles elucidated from this work can guide implant surface modifications toward an optimized surface geometry and profile to best fit and cell interactions for adequate bone growth.

Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes.

Large bone defects resulting from nonunion fractures or tumour resections are common clinical problems. Recent studies have shown bone morphogenetic protein-2 (BMP-2) gene transfer using adenoviral vectors to be a promising new therapeutic approach. However, comparative studies of different vectors are required to identify the optimal system for possible clinical trials. This study compares the use of liposome-mediated and adenoviral gene transfer for the generation of autologous BMP-2-producing bone marrow stromal cells (BMSC). Primary BMSC isolated from the rat femur were treated ex vivo with either an adenovirus or a liposome carrying human BMP-2 cDNA. The genetically modified cells were evaluated in vitro and transplanted into critical size defects in the rat mandible in vivo. BMSC treated with a reporter gene vector or untreated BMSC served as controls. The newly formed tissue was analysed by in situ hybridization, radiography and immunohistochemistry. Both groups of genetically modified cells produced BMP-2 for at least 2 weeks, and markers of new bone matrix such as osteopontin and osteocalcin were observed within 2 weeks following gene transfer. In the liposome group, the critical size defects were found completely healed at 6 weeks after the gene transfer, whereas the more efficient adenoviral gene transfer allowed for complete bone healing within 4 weeks. None of the three control groups showed bone healing, not even after 8 weeks. Thus, both liposome-mediated and adenoviral BMP-2 gene transfer to primary BMSC are suitable methods to achieve the healing of critical size bone defects in rats. As liposomes have proven sufficient for this purpose and offer several advantages over any other vector, such as ease of preparation, theoretically no limitation of the size of the DNA, and less immunological and safety problems, they may represent the best vector system for future clinical trials of bone regeneration by BMP-2 gene therapy.

In vivo evaluation of anodic TiO2 nanotubes: an experimental study in the pig.

Because of their ability to mimic the dimensions of constituent components of natural bone and the possibility to serve as a gene and drug-delivery carrier, nanotubes seem to be a promising coating for medical implants. Aim of this study was to investigate the effects of a TiO(2) nanotube structured surface on periimplant bone formation in vivo when compared with an untreated standard titanium surface. Twenty-five titanium implants covered with an ordered TiO(2) nanotube layer with an individual tube diameter of 30 nm and 25 commercially pure titanium (cp-Ti) implants were placed in the frontal skull of 25 domestic pigs. To evaluate the effects of the nanotube structured implants on the periimplant bone formation, bone-implant contact (BIC), and immunohistochemistry analysis were performed at day 3, 7, 14, 30, and 90. Evaluating immunohistochemistry, a significantly higher collagen type- I expression occurred at day 7 (p = 0.003), day 14 (p = 0.016), and day 30 (p = 0.044), for the nanostructured implants in comparison with the control group. It could be found that a nanotube structured implant surface with a diameter of 30 nm does influence bone formation and bone development by enhancing osteoblast function. SEM evaluation of the specimen surfaces revealed that the nanotube coatings do resist shearing forces that evoked by implant insertion. Because of their simple, low cost, flexible manufacturing and the possibility for the usage as drug or growth factor delivery system, nanotubes seem to be a promising method for future medical implant coatings.

Postoperative function after implant insertion in vascularized bone grafts in maxilla and mandible

&NA; Between 1988 and 1992, 80 Branemark‐type implants were inserted in 18 patients during reconstruction of the mandible or maxilla with vascularized iliac crest or scapula grafts with or without additional soft tissue pedicles. In these procedures, nine vascularized bone grafts were combined with a primary insertion of 32 implants and a secondary insertion of 48 implants. Twelve patients are currently wearing the implant‐borne dentures. From 32 implants inserted primarily, eight could not be used for prosthodontic rehabilitation because three were lost with a graft, three were left as sleepers, and two demonstrated a lack of osseointegration. None of the implants inserted secondarily in grafts were lost. Primary implant insertion should be performed only in close cooperation with the prosthodontist and in selected cases, for example, in freeend reconstruction of the mandible with a straight graft and where a limited number of implants is needed. Although restoration of masticatory function in patients with head and neck cancer can be achieved, compared with a healthy control group, functional impairments remain. Patients subjectively favor the nonreconstructed side of the mandible or maxilla for chewing. These findings can be correlated with a postoperative follow‐up investigation using a miniature force transducer and the T‐scan system. (Plast, Reconstr, Surg. 97: 719, 1996.)

In vivo performance of selective electron beam-melted Ti-6Al-4V structures.

Highly porous titanium structures are widely used for maxillofacial and orthopedic surgery because of their excellent mechanical properties similar to those of human bone and their facilitation of bone ingrowth. In contrast to common methods, the generation of porous titaniumproducts by selective electron beam melting (SEBM), an additive manufacturing technology, overcomes difficulties concerning the extreme chemical affinity of liquid titanium to atmospheric gases which consequently leads to strongly reduced ductility of the metal. The purpose of this study was to assess the suitability of a smooth compact and a porous Ti-6Al-4V structure directly produced by the SEBM process as scaffolds for bone formation. SEBM-processed titanium implants were placed into defects in the frontal skull of 15 domestic pigs. To evaluate the direct contact between bone and implant surfaces and to assess the ingrowth of osseous tissue into the porous structure, microradiographs and histomorphometric analyses were performed 14, 30, and 60 days after surgery. Bone ingrowth increased significantly during the period of this study. After 14 days the most outer regions of the implants were already filled with newly formed bone tissue (around 14%). After 30 days the bone volume inside the implants reached almost 30% and after 60 days abundant bone formation inside the implants attained 46%. During the study only scarce bone-implant contact was found around all implants, which did not exceed 9% around compact specimens and 6% around porous specimens after 60 days. This work demonstrates that highly porous titanium implants with excellent interconnectivity manufactured using the SEBM method are suitable scaffolds for bone ingrowth. This technique is a good candidate for orthopedic and maxillofacial applications.

Vascularization in the transition area between free grafted soft tissues and pre-irradiated graft bed tissues following preoperative radiotherapy in the head and neck region.

The healing of free vascular grafts in a pre‐irradiated graft bed is characterized by an increased risk of wound healing disorders. For that reason, the aim of this study was to examine quantitative vascularization pattern between free vascular grafts and the pre‐irradiated graft bed as a function of the preoperative irradiation dose.

Prospective study on post-traumatic and postoperative sensory disturbances of the inferior alveolar nerve and infraorbital nerve in mandibular and midfacial fractures

In a prospective study (January 1999 to December 1997), 34 patients with 26 mandibular and 20 midfacial fractures were investigated. All the fractures were managed by osteosynthesis. To evaluate the incidence and duration of recovery of post-traumatic and postoperative sensory disturbances, the following tests were carried out: sharp/blunt testing, and the two-point discrimination test as conventional clinical examination methods, and electromyographic recording of the masseter reflex to calibrate the clinical findings. To establish the sensory status of the inferior alveolar and the infraorbital nerves in the region of the fracture, and on the intact and control sides, the tests were performed pre-operatively and postoperatively on the seventh day, after 4 weeks and after 3, 6 and 12 months. The incidence of post-traumatic sensory disturbance was 46% for mandibular fractures and 65% for fractures to the midface (sharp/blunt test, two-point discrimination test). The rate of postoperative sensory disturbance in surgical treatment of mandibular fracture involving the region of the intra bony course of the inferior alveolar nerve, including the post-traumatic sensory disturbance, was 76.9%, and 55% following surgical treatment of midfacial fractures. The incidence of persistent sensory disturbances following surgical treatment was 7.7% in the case of mandibular fractures, and 15% in the case of midfacial fractures (sharp/blunt test, two-point discrimination test, masseter reflex). Recovery of neurological function is delayed in the presence of a displaced fracture (> 1 mm) as compared with non-displaced fractures. For the postoperative calibration of sensory disturbances, electromyographic recording of the masseter reflex from the fourth postoperative week onwards has proved useful.

Three-dimensional Analysis of Facial Symmetry in Cleft Lip and Palate Patients Using Optical Surface Data

Aim:Presentation of a new technique to determine the plane of symmetry of a face, and to assess the degree of facial symmetry in patients with unilateral cleft lip and palate based on three-dimensional (3D) optical surface data.Patients and Methods:After having determined a plane of symmetry according to optical 3D facial surface data, we identified differences in landmarks, the surface areas of the upper lip vermilion and nostrils and virtual volumes of the midface, nose and upper lip for cleft and unaffected sides in forty 10-year-old patients suffering from complete unilateral cleft lip, alveolus and palate. The children had undergone lip repair via the Tennison-Randall technique and had received subsequent orthodontic treatment (but not secondary osteoplasty).Results:Statistically significant differences were apparent between cleft and non-cleft sides in terms of the nasal landmarks, nostril angle and virtual volume of the nose. The upper lip was symmetrical when cleft and non-cleft sides were compared.Conclusions:This new technique of symmetry analysis reveals that the noses of 10-year-old patients with complete unilateral cleft lip and palate who had not undergone revisional surgery present a measurable and significant degree of asymmetry, while the upper lip is symmetrical as a consequence of interdisciplinary treatment by orthodontists and oral and maxillofacial surgeons. Further 3D analyses on larger numbers of patients will allow more comprehensive and consistent analysis of the potential and limitations of various surgical and conservative methods so as to identify those techniques with the best outcome in terms of facial symmetry.ZusammenfassungZiel:Ziel der Studie war es, eine neue Technik zur Beurteilung der Symmetrieebene des Gesichts auf Basis dreidimensionaler Datensätze vorzustellen und ihre Anwendung bei Patienten mit einseitiger Lippen-Kiefer-Gaumen-Spalte zu demonstrieren.Patienten und Methodik:Bei vierzig 10-jährigen Patienten mit einseitiger, vollständiger Lippen-Kiefer-Gaumen-Spalte, die bisher keine sekundäre Osteoplastik erhalten hatte, aber alle kieferorthopädisch behandelt wurden, erfolgte mit Hilfe von optischen 3-D-Daten der Gesichtsoberfläche und einer spezialisierten Software die Bestimmung der Symmetrieebene. Danach wurden die Unterschiede zwischen Landmarken, Flächen des Lippenrots und der Nasenlöcher sowie virtueller Volumina des Mittelgesichts, der Nase und der Oberlippe getrennt nach Gesichtshälften berechnet.Ergebnisse:Zwischen der Gesichtshälfte mit Spaltbildung und der Seite ohne Spalte bestanden statistisch signifikante Unterschiede in Bezug auf Landmarken, Winkel, Flächen und Volumina der Nasen. Im Bereich der Oberlippe wurden keine statistisch signifikanten Unterschiede zwischen der Spaltseite und der nicht betroffenen Seite bestimmt.Schlussfolgerungen:Die vorgestellte Technik der Symmetrieanalyse zeigt beim vorliegenden Patientengut, dass 10-jährige Patienten mit einseitiger Lippen-Kiefer-Gaumen-Spalte, die keine Korrekturoperationen im Verlauf erhielten, eine messbare, statistisch signifikante Asymmetrie der Nase aufweisen. Die Oberlippe dagegen ist bedingt durch das interdisziplinäre Behandlungskonzept aus kieferorthopädischen und mund-, kiefer- und gesichtschirurgischen Maßnahmen symmetrisch. Weitere dreidimensionale Analysen einer größeren Anzahl von Patienten werden die Möglichkeiten und Grenzen der verschiedenen operativen und konservativen Behandlungsmöglichkeiten herausstellen und die Auswahl des Behandlungskonzeptes erleichtern, das in Bezug auf die Gesichtssymmetrie mit den besten Ergebnissen aufwartet.

Validation of in vivo assessment of facial soft-tissue volume changes and clinical application in midfacial distraction: a technical report.

&NA; The purpose of this study was to validate the assessment of visible volume changes of the facial soft tissue with an optical three‐dimensional sensor and to introduce new parameters for the evaluation of the soft‐tissue shape achieved from three‐dimensional data of selected cases of midfacial distraction. Images of a truncated cone of known volume were assessed repeatedly with an optical three‐dimensional sensor based on phase‐measuring triangulation to calculate the volume. Two cubic centimeters of anesthetic solution was injected into the right malar region of 10 volunteers who gave their informed consent. Three‐dimensional images were assessed before and immediately after the injections for the assessment of the visible volume change. In five patients who underwent midfacial distraction after a high quadrangular Le Fort I osteotomy, three‐dimensional scans were acquired before and 6 and 24 months after the operation. The visible soft‐tissue volume change in the malar‐midfacial area and the mean distance of the accommodation vector that transformed the preoperative into the postoperative surface were calculated. The volume of the truncated cone was 235.26 ± 1.01 cc, revealing a measurement uncertainty of 0.4 percent. The injections of anesthetic solution into the malar area resulted in an average visible volume change of 2.06 ± 0.06 cc. The measurement uncertainty was 3 percent. In the five patients, the average distance of maxillary advancement was 6.7 ± 2.3 mm after 6 months and 5.4 ± 3.0 mm after 2 years. It was accompanied by a mean visible volume increase of 8.92 ± 5.95 cc on the right side and 9.54 ± 4.39 cc on the left side after 6 months and 3.54 ± 3.70 cc and 4.80 ± 3.47 cc, respectively, after 2 years. The mean distance of the accommodation vector was 4.41 ± 1.94 mm on the right side and 4.74 ± 1.32 mm on the left side after 6 months and 1.62 ± 1.96 mm and 2.16 ± 1.52 mm, respectively, after 2 years. The assessment of visible volume changes by optical three‐dimensional images can be carried out with considerable accuracy. The determination of volume changes and accompanying accommodation vectors completes the cephalometric analysis during the follow‐up of patients undergoing midfacial distraction. The new parameters will help to assess normative soft‐tissue data on the basis of three‐dimensional imaging with a view to an improved three‐dimensional prediction of the operative outcome of orthognathic surgery. (Plast. Reconstr. Surg. 112: 367, 2003.)

Osseointegration of endodontic endosseous conesZirconium oxide vs titanium

OBJECTIVE The purpose of this investigation was to investigate the osseointegration of zirconium oxide (ZrO(2)) ceramic cones in comparison with that of titanium cones in apicectomy. STUDY DESIGN To evaluate the bone/implant interface, 20 ZrO(2) cones and 20 titanium cones were inserted into the mandibles of 4 Göttinger minipigs. During the 6-month healing period, intravital polychrome sequence marking was performed. Qualitative light microscopic, fluorescence microscopic, and quantitative histomorphometric assessment was carried out. Differences between continuous histomorphometric measures were tested through use of a 2-way analysis of variance. RESULTS Light microscopy revealed zones of direct bone contact with the ZrO(2) and titanium surfaces. Fluorescence microscopy revealed remodeling processes directly adjacent to both material surfaces. There was no significant difference in the distances of the fluorescence bands of each fluorescence marker for either the ZrO(2) surfaces or the titanium surfaces. Quantitatively and histomorphometrically, the mean ratio between the total cone/bone contact and the total cone/fibrous tissue contact was 0.95 (SD 1.10) on the titanium surface (n = 38) and 1.47 (SD 1.12) on the ZrO(2) surface (n = 78; P =.02). CONCLUSIONS The qualitative results show that the biocompatibility of ZrO(2) was similar to that of titanium. The use of ZrO(2) cones for sealing purposes in resected teeth after apicectomy appears to be acceptable.