Jörg Wiltfang

Different preparation methods to obtain platelet components as a source of growth factors for local application

BACKGROUND: Autologous platelet components were recently used as part of tissue‐engineering strategies in oral and maxillofacial surgery. Various preparation methods were investigated to define standardized blood bank components and to collect data on the growth factor content of human platelets before and after storage.

Bis-phossy jaws - high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw.

INTRODUCTION Bisphosphonates (BPs) have transformed our ability to treat certain malignancies, osteoporosis and hypercalcaemia. This class of drug is assumed to be well tolerated by most. There are some important caveats to this assumption, however, one of the significances being the risk of osteonecrosis of the jaw (ONJ). MATERIAL AND METHODS This multi-centre retrospective study examined the role of different BPs on the development of ONJ, its clinical presentation and the efficacy of various treatment modalities, comparing these findings with the available literature. RESULTS A total of 78 patients from 17 centres were identified with ONJ. A majority of patients identified with ONJ had used Pamidronate or Zoledronate (93.6%) intravenously. 94.9% of patients had received BP in the course of treatment for malignancies and a majority had also received prior chemotherapy or exogenous steroids. 82.1% of patients had received BP for more than 1 year. The mean time from the introduction of BP to the development of ONJ in 24 patients from our department was 31.8 months. CONCLUSIONS The most common intraoral manifestation was exposed necrotic jawbone. Tooth extractions and oral surgical intervention appear to place patients on BP therapy at risk of ONJ, especially after intravenous BP treatments. ONJ proved in this study to be remarkably refractory to treatment, with radical resection being the only curative approach. We recommend that all patients receive necessary dental treatment prior to commencing BP therapy.

Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence – a multi-centre study

INTRODUCTION Bisphosphonates (BPs) are powerful drugs that inhibit bone metabolism. Adverse side effects are rare but potentially severe such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, research has primarily focused on the development and progression of BRONJ in cancer patients with bone metastasis, who have received high dosages of BPs intravenously. However, a potential dilemma may arise from a far larger cohort, namely the millions of osteoporosis patients on long-term oral BP therapy. PATIENTS AND METHODS This current study assessed 470 cases of BRONJ diagnosed between 2004 and 2008 at eleven different European clinical centres and has resulted in the identification of a considerable cohort of osteoporosis patients suffering from BRONJ. Each patient was clinically examined and a detailed medical history was raised. RESULTS In total, 37/470 cases (7.8%) were associated with oral BP therapy due to osteoporosis. The majority (57%) of affected individuals did not have any risk factors for BRONJ as defined by the American Association of Oral and Maxillofacial Surgery. The average duration of BP intake of patients without risk factors was longer and the respective patients were older compared to patients with risk factors, but no statistical significant difference was found. In 78% of patients the duration of oral BP therapy exceeded 3 years prior to BRONJ diagnosis. DISCUSSION The results from this study suggest that the relative frequency of osteoporosis patients on oral BPs suffering from BRONJ is higher than previously reported. There is an urgent need to substantiate epidemiological characteristics of BRONJ in large cohorts of individuals.

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.

Ceramic scaffolds produced by computer-assisted 3D printing and sintering: Characterization and biocompatibility investigations

Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. However, in general HAP and TCP scaffolds are not tailored to the exact dimensions of the defect site and are mainly used as granules or beads. Some scaffolds are available as ordinary blocks, but cannot be customized for individual perfect fit. Using computer-assisted 3D printing, an emerging rapid prototyping technique, individual three-dimensional ceramic scaffolds can be built up from TCP or HAP powder layer by layer with subsequent sintering. These scaffolds have precise dimensions and highly defined and regular internal characteristics such as pore size. External shape and internal characteristics such as pore size can be fabricated using Computer Assisted Design (CAD) based on individual patient data. Thus, these scaffolds could be designed as perfect fit replacements to reconstruct the patients skeleton. Before their use as bone replacement materials in vivo, in vitro testing of these scaffolds is necessary. In this study, the behavior of human osteoblasts on HAP and TCP scaffolds was investigated. The commonly used bone replacement material BioOss(R) served as control. Biocompatibility was assessed by scanning electron microscopy (SEM), fluorescence microscopy after staining for cell vitality with fluorescin diacetate (FDA) and propidium iodide (PI) and the MTT, LDH, and WST biocompatibility tests. Both versions were colonised by human osteoblasts, however more cells were seen on HAP scaffolds than TCP scaffolds. Cell vitality staining and MTT, LDH, and WST tests showed superior biocompatibility of HAP scaffolds to BioOss, while BioOss was more compatible than TCP. Further experiments are necessary to determine biocompatibility in vivo. Future modifications of 3D printed scaffolds offer advantageous features for Tissue Engineering. The integration of channels could allow for vascular and nerve ingrowth into the scaffold. Also the complex shapes of convex and concave articulating joint surfaces maybe realized with these rapid prototyping techniques.

Platelet-rich Plasma and Platelet-rich fibrin in human cell culture

OBJECTIVES The clinical use of platelet-rich plasma (PRP) for preprosthetic surgery has been a matter of controversy until now. Only recently, a new blood preparation has been developed which results in platelet-rich fibrin (PRF). The objective of the present investigation was to examine the growth factor release from PRP and PRF in vitro. STUDY DESIGN Whole blood samples from healthy participants (n = 10) were drawn to generate PRP and PRF. Human osteoblasts (O), human fibroblasts (F), and human osteoblast-derived osteosarcoma cells (Saos-2) were used for the cell culture. Cells of each cell line were cultivated, and PRP- or PRF-preparations added for ten days. The drawn medium was pooled and the quantities of growth factors (platelet-derived growth factor isomers AB and BB, insulin-like growth factor I, and transforming growth factor (TGF) isomers beta1 and beta2) analyzed by enzyme-linked immunosorbent assay. RESULTS In osteoblast and Saos-2 cultures, cytokine concentrations were significantly higher for PRP than for PRF (P < .05). In fibroblast cultures, results were the same with the exception of TGF-beta2 (P < .05). CONCLUSIONS This study demonstrates that PRP application in cell cultures leads to higher levels of growth factors than PRF application.

Platelet‐rich fibrin membranes as scaffolds for periosteal tissue engineering

OBJECTIVES Platelet-rich fibrin (PRF)-based membranes have been used for covering alveolar ridge augmentation side in several in vivo studies. Few in vitro studies on PRF and no studies using human periosteal cells for tissue engineering have been published. The aim is a comparison of PRF with the commonly used collagen membrane Bio-Gide as scaffolds for periosteal tissue engineering. MATERIAL AND METHODS Human periosteal cells were seeded on membrane pieces (collagen [Bio-Gide] and PRF) at a density of 10(4) cells/well. Cell vitality was assessed by fluorescein diacetate (FDA) and propidium iodide (PI) staining, biocompatibility with the lactate dehydrogenase (LDH) test and proliferation level with the MTT, WST and BrdU tests and scanning electron microscopy (SEM). RESULTS PRF membranes showed slightly inferior biocompatibility, as shown by the LDH test. The metabolic activity measured by the MTT and WST tests was higher for PRF than for collagen (BioGide). The proliferation level as measured by the BrdU test (quantitative) and SEM examinations (qualitative) revealed higher values for PRF. CONCLUSION PRF appears to be superior to collagen (Bio-Gide) as a scaffold for human periosteal cell proliferation. PRF membranes are suitable for in vitro cultivation of periosteal cells for bone tissue engineering.

Intraindividual Comparative Animal Study of α- and β-Tricalcium Phosphate Degradation in Conjunction with Simultaneous Insertion of Dental Implants

An intraindividual comparative study of proximal tibial marrow defects in nine adult Goettinger miniature pigs (GMPs) was undertaken. The left side of the defect was filled with granular &bgr;-tricalcium phosphate (TCP) ceramic ad modum Cerasorb, and the right side was filled with granular &agr;-TCP ceramic ad modum Biobase &agr; pore. Simultaneously, dental screw implants were inserted in each ceramic and fixed within the orthotopically replanted corticalis lids. Control defects were made in two other animals. The survival period ranged from 4 to 86 weeks (control study, 16 and 20 weeks). The reorganization and degree of bone regeneration, dynamics of ceramic degradation, and remodeling characteristics of the bone regenerate referring to osseo-integration of the dental implants were examined histomorphologically in nondecalcified specimens. The results reveal that both ceramic types were osteoconductive exclusively. Centripetally oriented angiogene bone regeneration occurred at the margins of the circular defects. Ceramic degradation was performed hydrolytically and within cells. Furthermore, it was demonstrated that decomposition of the intratrabecularly integrated ceramic residues underlies a dynamic process of degradation. Within 86 weeks, nearly 80% to 90% of the larger &agr;-TCP granules, and nearly 90% to 95% of the &bgr;-TCP granules were degraded. At this time, especially for the &agr;-TCP modification, ceramic microparticles were found in the marrow, either unbound or within polynuclear macrophages. The predictable degradation of both ceramic types provides an early functional adaptation of bone regenerates and facilitates a biofunctional, anisotropic orientation of the neotrabeculae without delay. It is concluded that because of the initially pronounced accumulation of macrophages, dental implants should not be inserted simultaneously with ceramic, but after further progress of ceramic degradation (5 to 6 months after TCP implantation).

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.

Long-term results of distraction osteogenesis of the maxilla and midface

Since the beginning of 1998, eight patients have been treated by osteodistraction to correct hypoplasia of the maxilla and midface of various origins. Among them were five patients who were treated by high LeFort I osteotomies and insertion of subcutaneous intraoral distraction devices in the malar region. In the remaining three patients, extraoral distraction devices were applied after LeFort II and III osteotomies. Distraction osteogenesis was successful in all cases, resulting in a mean sagittal bone gain measured parallel to the skull base of 9.0 mm (range 4.5-12.0) in the group treated with intraoral distractors and a mean of 20.3 mm in the extraoral distraction group (range 15.0-25.0). All patients were kept under orthodontic supervision before, during, and after osteodistraction. Long-term cephalometric and clinical evaluation after a mean follow-up period of 24 months in the intraoral distraction group (range 22-26) and 12 months in the extraoral distraction group (range 10-14) show stable results concerning the skeletal and dental relations. Long-term follow-up is necessary.