Susanne Jung

Release kinetics of VEGF165 from a collagen matrix and structural matrix changes in a circulation model

BackgroundCurrent approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model.MethodsRelease kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with light microscopy, native scanning electron microscopy (SEM) as well as with immuno-gold-labelling technique in scanning and transmission electron microscopy (TEM).ResultsWe established a biological half-life for VEGF165 of 90 minutes. In a half-logarithmic presentation the VEGF165 release showed a linear declining gradient; the release kinetics were not depending on VEGF165 concentrations. After 12 hours VEGF release reached a plateau, after 48 hours VEGF165 was no longer detectable in the complexes charged with lower doses, but still measurable in the 80 μg sample. At the beginning of the study a smear layer was visible on the surface of the complex. After the wash out of the protein in the first days the natural structure of the collagen appeared and did not change over the test period.ConclusionsBy defining the pharmacological and morphological profile of a cytokine collagen complex in a circulation model our data paves the way for further in-vivo studies where additional biological side effects will have to be considered. VEGF165 linked to collagen fibrils shows its improved stability in direct electron microscopic imaging as well as in prolonged release from the matrix. Our in-vitro trial substantiates the position of cytokine collagen complexes as innovative and effective treatment tools in regenerative medicine and and may initiate further clinical research.

Quantification of facial asymmetry by 2D analysis – A comparison of recent approaches

INTRODUCTION Symmetry has been found to play a crucial role in attractiveness assessment and so its restoration is an essential problem in oral maxillofacial surgery. This paper presents an overview of recent 2D asymmetry analysis techniques. These are techniques which are based on the evaluation of two-dimensional data, like photos. The aim of this paper is to find the most precise and practical techniques to investigate facial asymmetry. MATERIALS AND METHODS For this purpose studies addressing symmetry investigations are collected and categorized by the type of data they extract from the photos. The reference points on the facial surface, which are frequently used in these studies, are presented and calculation methods are described. RESULTS Three kinds of techniques using vertical or horizontal reference lines or centres of bilateral points appear to be most appropriate. Recommendations are made, which aspects should be taken into account when calculating symmetry/asymmetry indices from photos. Advantages and disadvantages of the three selected methods are summarized in a table. CONCLUSIONS Using one of the three recommended approaches denoted by FA, AI and z-score allows calculating meaningful asymmetry values. The proper selection and identification of reference points is crucial. For highest accuracy, a sufficient number of evenly distributed and reproducible reference points should be used.

Measured symmetry of facial 3D shape and perceived facial symmetry and attractiveness before and after orthognathic surgery.

One aim of cranio-maxillo-facial surgery is to strive for an esthetical appearance. Do facial symmetry and attractiveness correlate? How are they affected by surgery? Within this study faces of patients with orthognathic surgery were captured and analyzed regarding their symmetry. A total of 25 faces of patients were measured three-dimensionally by an optical sensor using the fringe projection technique before and after orthognathic surgery. Based upon this data an asymmetry index was calculated for each case. In order to gather subjective ratings each face was presented to 100 independent test subjects in a 3D rotation sequence. Those were asked to rate the symmetry and the attractiveness of the faces. It was analyzed to what extend the ratings correlate with the measured asymmetry indices and whether pre- and post-surgical data differ. The measured asymmetry indices correlate significantly with the subjective ratings of both items. The measured symmetry as well as the rated symmetry and attractiveness increased on average after surgery. The increase of the ratings was even statistically significant. A larger enhancement of symmetry is achieved in pre-surgical strongly asymmetric faces than in rather symmetric faces.

Dental implants in cleft lip, alveolus, and palate patients: a systematic review.

PURPOSE Missing teeth are a major problem in cleft patients, who require specialized prosthetic management, including dental implants. The aim of this review was to investigate the optimal date for implant insertion in patients born with cleft lip and palate after bone grafting and to assess the long-term prognosis of the inserted dental implants. MATERIALS AND METHODS A systematic review of the current literature electronically in several databases and additional hand searching were performed. Relevant publications were assessed with regard to their evidence according to the guidelines of the Oxford Centre for Evidence-Based Medicine. RESULTS Forty-nine publications (prospective and retrospective clinical studies, case series, and case reports) were included for analysis, but only 18 clinical papers reported survival rates for dental implants (in all, 670 implants in 460 cleft patients). Most studies were evidence level 3b (case-control studies) or 4 (case series, case reports). Reported 5-year survival rates for dental implants in cleft patients ranged from 80% to 96% (mean, 88.6%). Implant placement is favored after growth is complete and is generally recommended within 4 to 6 months after bone grafting. CONCLUSIONS Dental implants in patients with cleft lip and palate show high success rates and allow for sufficient oral rehabilitation. However, because of a lack of sufficient prospective clinical studies on dental implants in cleft patients, the available evidence is poor and insufficient.

Nasopharyngeal Development in Patients with Cleft Lip and Palate: A Retrospective Case-Control Study

Introduction. The aim of this paper was to evaluate cephalometrically the nasopharyngeal development of patients with complete unilateral cleft lip and palate. Influencing factors were evaluated and cleft to noncleft subjects were compared to each other. Material and Methods. The lateral cephalograms of 66 patients with complete cleft lip and palate were measured and compared retrospectively to the cephalograms of 123 healthy probands. Measurements were derived from a standardized analysis of 56 landmarks. Results. We observed significant differences between cleft and control group: the cleft patients showed amaxillary retroposition and a reduced maxillary length; the inclination of the maxilla was significantly more posterior and cranial; the anterior nasopharyngeal height was reduced; the nasopharyngeal growth followed a vertical tendency with reduced sagittal dimensions concerning hard and soft tissue. The velum length was reduced. In the cleft group, an accumulation of mandibular retrognathia and an anterior position of the hyoid were observed. Skeletal configuration and type of growth were predominantly vertical. Conclusions. Our data provides a fundamental radiological analysis of the nasopharyngeal development in cleft patients. It confirms the lateral cephalogram as a basic diagnostic device in the analysis of nasopharyngeal and skeletal growth in cleft patients.

Results of speech improvement following simultaneous push-back together with velopharyngeal flap surgery in cleft palate patients

OBJECTIVE Velopharyngeal insufficiency (VPI) can be caused by a variety of disorders. The most common cause of VPI is the association with cleft palate. The aim of this study was to evaluate the effectiveness of different surgical techniques for cleft palate patients with VPI: (1) velopharyngoplasty with an inferiorly based posterior pharyngeal flap (VPP posterior, Schönborn-Rosenthal), and (2) combination of VPP posterior and push-back operation (Dorrance). PATIENTS AND METHODS 41 subjects (26 females, 15 males) with VPI were analysed. Hypernasality was judged subjectively and nasalance data were assessed objectively using the NasalView system preoperative and 6 months postoperative. RESULTS Subjective analysis showed improved speech results regarding hypernasality for all OP-techniques with good results for VPP posterior and VPP posterior combined with push-back with success rates of 94.4% and 87.7%, respectively. Objective analysis showed a statistically significant reduction of nasalance for both VPP posterior and VPP posterior combined with push-back (p < 0.01). However, there were no statistically significant differences concerning measured nasalance values postoperatively between the VPP posterior and VPP posterior combined with push-back. CONCLUSION Based on our findings, both VPP posterior and VPP posterior combined with push-back showed good results in correction of hypernasality in cleft patients with velopharyngeal insufficiency.

Regenerative potential of human adipose-derived stromal cells of various origins.

In regenerative concepts, the potential of adult stem cells holds great promise concerning an individualized therapeutic approach. These cells provide renewable progenitor cells to replace aged tissue, and play a significant role in tissue repair and regeneration. In this investigation, the characteristics of different types of adipose tissue are analysed systematically with special attention to their proliferation and differentiation potential concerning the angiogenic and osteogenic lineage. Tissue samples from subcutaneous, visceral, and omental fat were processed according to standard procedures. The cells were characterized and cultivated under suitable conditions for osteogenic and angiogenic cell culture. The development of the different cell cultures as well as their differentiation were analysed morphologically and immunohistochemically from cell passages P1 to P12. Harvesting and isolation of multipotent cells from all three tissue types could be performed reproducibly. The cultivation of these cells under osteogenic conditions led to a morphological and immunohistochemical differentiation; mineralization could be detected. The most stable results were observed for the cells of subcutaneous origin. An osteogenic differentiation from adipose-derived cells from all analysed fatty tissues can be achieved easily and reproducibly. In therapeutic concepts including angiogenic regeneration, adipose-derived cells from subcutaneous tissue provide the optimal cellular base.

Angiogenesis — The Key to Regeneration

The fundament of regeneration is the tissue’s potential to grow, to differentiate and therefore to continually bridge permanently emerging damages. It is a stepless coexistence of build-up and degradation processes in which a plethora of enzymes, signal proteins, ligands and their corresponding receptors on different regulatory levels are involved. These processes concern every part of the body; the least common denominator of all these physiological events that include a transition from single cells to a complex tissue structure is their demand for energy and substrates. It becomes obvious that there can never arise a regenerative course without a functioning vasculature to provide the essential cells and proteins, to ensure the oxygen and nutrient supply and to evacuate accumulating metabolic products. Any regeneration is only able to develop with a simultaneously developing vessel system. The realisation seems to be trivial, but the vital importance of a functional vasculature is not generally considered in regenerative concepts.

Objective Assessment of Hypernasality in Patients with Cleft Lip and Palate with the NasalView System: A Clinical Validation Study.

Introduction. The objective of this investigation was to evaluate the reliability and validity of the NasalView system as a screening tool for hypernasality within the scope of a routine diagnostic procedure in cleft lip and palate patients. Material and Methods. In a collective of 95 patients with cleft and lip palate ranging from 4 to 25 years of age, hypernasality was exploited perceptually, patients were classified in four degrees, and nasalance was measured objectively with the NasalView system. Speech stimuli existed in one nasal and one nonnasal sentence; nasalance ratio and distance were calculated. Results. The test-retest error was within a range of 2%. Sensitivity ranged from 83.3% to 91.1% for the nonnasal sentence, from 70% to 78.4% for nasalance ratio and from 68.1% to 81.1% for nasalance distance. Specifity ranged from 87% to 93.1% for the nonnasal sentence, from 69.6% to 97.5% for nasalance ratio, and from 70.7% to 73.9% for nasalance distance. Conclusions. With a quick and gentle screening procedure, it is easily possible to identify hypernasal patients by an objective diagnostic tool of hypernasality, the NasalView system, with good reliability and validity.

Measuring facial symmetry: a perception-based approach using 3D shape and color

Abstract Objective: Facial symmetry is an important factor affecting esthetics. Thus, its restoration is an essential task in maxillofacial surgery. The aim of this study is to develop an objective measure of facial asymmetry by a novel approach where both the shape and the color are taken into account and to validate its correlation with perception. Methods: Optical three-dimensional (3D) face scans of 30 healthy adults are performed. Face-specific asymmetry indices are calculated by quantifying color differences as well as spatial distances between 3D data of a face and its mirrored copy. Subjective ratings of symmetry and attractiveness of the faces by 100 subjects are used to validate these indices. Results: The symmetry ratings show significant correlations with color and geometric asymmetry indices. The attractiveness ratings correlate only weakly with both indices. However, the product of the indices exhibits significant correlations with both attractiveness and symmetry ratings. Conclusion: The presented combined asymmetry index comprising shape and coloring turned out to reflect subjective perception of both facial symmetry and attractiveness. It thus promises to be a valid objective measure for facial esthetics, which could contribute, e.g., to the evaluation of surgical methods as well as to the design of craniofacial prostheses.