Luca Raffaelli

Development of a new zirconia-toughened alumina: promising mechanical properties and absence of in vitro carcinogenicity.

High purity alumina as well as zirconia ceramics have been widely used as orthopaedic implant biomaterials and dental devices displaying optimal, but sometimes exclusive, mechanical properties. In order to combine the advantages of alumina and zirconia ceramic materials different types of composites have been developed in which either zirconia is dispersed in an alumina matrix or vice versa. Orthopaedic and dental implant biomaterials are expected to be in contact with living tissues for a long period of time and their long term toxicity must be carefully evaluated. In this study we report the development of a high performance chromia-doped Zirconia Toughened Alumina (ZTA) material which displays promising mechanical properties in terms of hardness, strength and fracture toughness that make it suitable for prosthesis even for small joints. The long-term biocompatibility of this material was also evaluated, mainly in terms of DNA damage, mutagenicity and cancerogenetic potential in mammalian cells. The results obtained suggest that this new ZTA material does not display any long-term carcinogenic effect and it is suitable for biomedical applications from a cancerogenetic point of view. In conclusion, we report the development of a new chromia-doped ZTA material with interesting properties both from a mechanical and a biocompatibility point of view which warrant further studies on its suitability as a candidate biomaterial for orthopaedic implants and dental devices.

An overview about biomedical applications of micron and nano size tantalum.

Tantalum is obtained from the minerals colombite, tantalite and euxenite. It is greyish silver, heavy and very hard. Tantalum does not react with body fluids and is used to make surgical equipment. Tantalum also does not irritate the body and is used to make surgical sutures as well as implants, such as artificial joints and cranial plates. Bone growth around tantalum covered by calcium phosphate is described by in vitro experimentations. in vivo. Bioactive properties of porous tantalum have been recently developed. Porous tantalum consists of an interconnected porous structure with an average porosity diameter of approximately 400 microm. Hollow spheres with nanometre-to-micrometer dimensions are widely used in different range of applications such as drug delivery carriers and bioreactors. Porous tantalum metal is currently used in orthopaedic for manufacturing of structural component for primary and revision total hip and knee replacements and, more recently, in spine surgery. Good clinical outcomes have been achieved especially in hip revision surgery, using tantalum implants, and promising short term follow up have been reported for knee revision surgery. Some patents for tantalum biomedical applications have been obtained and this article reviews various recent patents on this material. Many patents are developed on tantalum for biomedical application. This paper review some of them with particular interested for biomedical applications in orthopaedic and dentistry.

N-3 polyunsaturated fatty acid effect in periodontal disease: state of art and possible mechanisms involved.

Anti-inflammatory properties have been widely reported for n-3 polyunsaturated fatty acids (PUFAs) and some studies have been focalized on their possible role in the modulation of gingivitis and alveolar bone resorption in periodontal disease (PD). Increased formation of arachidonic acid-derived inflammatory eicosanoids and augmented oxidative stress are two molecular mechanisms pathogenetically involved in the progression of PD and known to be inhibited by n-3 PUFAs in PD setting. The present review will focus also on other molecular pathways and factors known to be altered in the development of PD and known to be subject to n-3 PUFA modulation in other pathological settings different from PD. Overall, the available findings strongly encourage further experimental studies on animals subject to experimental PD and treated with n-3 PUFAs, long term n-3 PUFA intervention studies on PD patients and molecular studies to identify additional potential molecular routes of n-3 PUFA action in PD.

Periodontopathogen and Epstein-Barr Virus Contamination Affects Transplanted Bone Volume in Sinus Augmentation

BACKGROUND Bone microbial contamination can impair osteogenesis. Human herpesviruses-associated vasculitis can cause vascular damage within the osseous graft and host. This study is conducted to substantiate specific contamination and assess the impact 6 months after sinus augmentation. METHODS Culture- and polymerase chain reaction (PCR)-based identification were done on harvested bone particles and unstimulated whole saliva in a group of 30 patients undergoing maxillary sinus augmentation. Patients were divided into two groups: those with and those without a history of periodontitis. Radiographic evaluation was done to assess and compare bone healing and volume gain at baseline and 6 months post-transplantation. RESULTS Seventeen patients had a history of periodontitis, and 13 did not. Ten showed culture- and PCR-negative results and belonged to the periodontally healthy group. The 17 patients with periodontitis showed culture- or PCR-positive results for the targeted periodontal pathogens. Patients with periodontitis were 2.3 times more likely to have positive salivary Epstein-Barr virus type 1 (EBV-1) than those with no history of periodontitis. The likelihood of having moderate to pronounced bone volume loss 6 months postaugmentation was 7.5 times greater in those patients presenting contamination with ≥3 specific pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, or Prevotella intermedia) versus those with only one (P <0.05). The odds ratio (OR) of pronounced volume loss was 16.3 times higher in those contaminated with a combination of salivary EBV-1 and ≥3 of the previously mentioned species versus only EBV-1 (P <0.05). Individuals showing positive salivary EBV-1 had bone bacterial contamination associated 57% of the time. The OR of having bone microbial contamination in patients with a history of periodontitis was 37.5 times higher than in individuals without periodontitis. CONCLUSIONS This study confirms contamination of bone, harvested intraorally, with key periodontopathogens in individuals undergoing sinus augmentation. Specific microbial contamination can impair osteogenesis. Saliva may act as a vehicle to transport EBV and other pathogens into the sinus. Increased bone volume loss seems to be associated with the occurrence of specific periodontal anaerobic species, salivary EBV-1, or the combination of both.

Alumina and Zirconia Ceramic for Orthopaedic and Dental Devices

Ceramic materials are made of an inorganic non-metallic oxide. Usually ceramics are divided into two groups: silicon ceramics and aluminous ceramics. Ceramics are also divided into crystalline and non-crystalline depending on inner molecular organization. Depending on their in vivo behaviour, ceramics are classified as bioresorbable, bioreactive or bioinert. Alumina and zirconia are bioinert ceramics; their low reactivity togheter with their good mechanical features (low wear and high stability) led to use them in many biomedical restorative devices. Their most popular application is in arthroprosthetic joints where they have proven to be very effective, that make their use suitable especially in younger, more active patients. Also dental use of these materials was proposed to achieve aesthetic and reliability of dental restorations.

In vivo characterization of Zirconia Toughened Alumina material: a comparative animal study.

The development of a new chromia-doped Zirconia Toughened Alumina (ZTA) material was previously reported as displaying mechanical properties suitable for implants with load bearing applications, such as orthopaedic and dental implants. This type of biomaterial is expected to be in contact with living tissues for a long period of time and its long-term toxicity must be carefully evaluated. In this study the suitability of this ZTA material as a candidate biomaterial for orthopaedic implants and dental devices was further investigated in vivo in comparison to alumina and zirconia, which are currently used in orthopaedic and dental surgery. Cylinders of the materials were implanted in vivo in white rabbits, and local and systemic tissue reactions were analyzed at different time intervals after surgery. Radiologic examinations displayed the absence of radiolucence around cylinders and no signs of implant loosening up to twelve months. No tumours developed in the animals either locally (at the site of implantation), or systemically in the peripheral organs. The results obtained suggest that this new ZTA material does not display any long term pathogenic effect in vivo. These findings extend our previous observations on the biocompatibility and the absence of any long-term carcinogenic effect in vitro of this material which displays interesting properties for biomedical applications. In conclusion, we report the in vivo characterization of a new chromia-doped ZTA material and confirm its suitability as a candidate biomaterial for orthopaedic implants and dental devices since it does not give any local nor systemic toxicity even after a long period of time after implantation.

Computer-Aided Design Evaluation of Harvestable Mandibular Bone Volume: A Clinical and Tomographic Human Study

PURPOSE To evaluate and compare the volume of bone graft material that can be safely harvested from the mandibular symphysis and rami using a computer-aided design (CAD) software program. MATERIALS AND METHODS Preoperative computerized tomography scans from 40 patients undergoing bone augmentation procedures were analyzed. Symphysis and rami cross sections were mapped using a CAD software program (AutoCAD(®), Autodesk, Inc., San Rafael, CA, USA) to evaluate the bone volume that can be safely harvested. CAD calculations were contrasted to intrasurgical measurements in a subgroup of 20 individuals. RESULTS CAD calculations yielded a safe harvestable osseous volume of 1.44 cm(3) ± 0.49 for the symphysis and 0.82 cm(3) ± 0.21 for each ramus (p < .0001, confidence interval [CI] 95%: 0.47-0.78). These measurements were significantly lower (p < .0001) than the bone volumes harvested intrasurgically for both symphysis and ramus, respectively (2.40 cm(3) ± 0.50 vs. 2.65 cm(3) ± 0.45). CAD calculations of harvestable symphysis and ramus bone translated into an average of 2.40 cm(3) ± 0.50 (range: 1.80-3.10 cm(3)) and 2.65 cm(3) ± 0.45 (range: 1.90-3.50) of particulate bone graft intrasurgically, respectively. Ramus cortical was significantly thicker than the symphysis cortical, 2.9 ± 0.4 mm versus 2.19 mm ± 0.4 mm (p < .0001, CI 95%: 0.45-1.03). CONCLUSION The symphysis and rami are good harvesting sources to obtain dense corticocancellous bone. The significant volumetric CAD differences between the symphysis and ramus seem to balance out intrasurgically and may be due to the greater cortical bone volume at the ramus area. It is plausible to harvest an average of 7.70 cm(3) from the symphysis and rami alone. The use of a CAD software program can enhance surgical treatment planning prior to bone transplantation.

Morphological Modifications in Osteoarthritis: A Scanning Electron Microscopy Study

The chondrocyte, the only cellular component of adult articular cartilage, plays a key role in the pathogenesis of osteoarthritis (OA). The evolution of this process is very slow: the first changes involve the cell-matrix morphofunctional unit known as chondron. In this study we analyzed the cartilage of 10 patients with primary osteoarthritis. The cartilage was retrieved during total knee replacement (TKR) and maxillofacial surgery procedures. All patients presented an osteoarthritis of at least grade III. The preparation of the specimens was made by taking cartilage from both well-preserved and macroscopically degenerated areas. Specimens underwent histological evaluation with conventional staining and ultrastructural analysis. Age appeared to be a high risk factor in the development of articular cartilage damages. Depth of injury was also found to be age-related as more extensive lesions were found in the elderly, either in the knee or in the mandibular condyle. Whatever the cause of possible damage, Scanning Electron Microscopy (SEM) observations showed that at the beginning most degenerative changes in articular cartilage involved the chondron unit, a concept first introduced by Benninghoff. These changes generally go through three phases. During OA progression all degenerative changes begin from the chondron, which is why it is extremely important to understand the molecular anatomy and physiology of this pericellular microenvironment and its form, function and failure in adult articular cartilage. It is also fundamental to understand the mechanism of adaptation of the cartilage and bone disruptions, given the physiological relationship between these tissues, essential to maintain normal joint structure and function.

Examination of periodontal pathogens in stenotic valve specimens and in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis

Periodontitis may be a risk factor for atherosclerosis and coronary heart disease. The influence of periodontal pathogens in cardiovascular diseases needs further investigation. Therefore, the aims of this clinical study are: to test the presence of periodontal bacteria DNA in aortic valves and to assess the concomitant presence of the same periodontal bacteria DNA in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis. Nineteen consecutive patients (12 males and 7 females, age: 49–85 years) were enrolled in this study after having been subjected to a complete periodontal evaluation to confirm the diagnosis of chronic periodontitis. All patients were scheduled for aortic valve replacement surgery. After clinical and microbial periodontal examination, the aortic valve tissue specimens were obtained by excision during valve replacement surgery and the patients were subjected to the whole blood sampling before the surgery. The polymerase chain reaction technology was used to detect the putative periodontal pathogens Tannerella forshytia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens and Treponema denticola. Neither the 19 aortic valve specimens nor the blood samples were positive for the genoma of the selected periodontal pathogens. The selected periodontal pathogens did not colonize the aortic valve of patients affected by stenosis and bacterial genoma was not present in whole blood samples. A high blood pressure at the aortic valve may prevent the adhesion and proliferation of bacterial colonies.

Interobserver variability of dynamic MR imaging of the temporomandibular joint

PurposeThis study investigated the interobserver variability of dynamic magnetic resonance (MR) imaging of the temporomandibular joint (TMJ).Materials and methodsSixty-two patients with internal derangement of the TMJ (124 TMJs) were investigated with a 1.5-T MR imaging system during physiological opening and closing of the mouth. Two readers evaluated independently the quality of the dynamic examination (Q: nondiagnostic, diagnostic, optimal), condylar motion (CM: limited, suboptimal, optimal), condylar orientation (CO: in-plane, through-plane shift), disc visibility and movement (DV: visible, nonvisible; DM: normal, reducing, nonreducing dislocation) and joint effusion (JE: present, absent). For each TMJ, the condylar path was measured by tracing the position of the condyle in the frames of the dynamic acquisition. Agreement between the two readers was assessed with Cohen’s Kappa and the Bland-Altman method.ResultsInterobserver agreement was almost perfect for Q (nondiagnostic, diagnostic, optimal: 0.8%, 4.9%, 94.3%; κ=1), CM (limited, suboptimal, optimal: 14%, 26.4%, 59.5%; κ=0.84) and DV (visible, nonvisible: 100%, 0%). Substantial agreement was found for DM (normal, reducing, nonreducing: 66.1%, 14.8%, 19.1%; κ=0.64) and JE (present, absent: 41.3%, 58.7%; κ=0.67). Moderate agreement was found for CO (in-plane, through-plane shift: 94.2%, 5.8%; κ=0.41). As for the condylar path, the means of the percentage differences and limits of agreement (LA) were −3% (LA: −34.5%, 28.3%) on the right and −1.2% (LA: −35%, 32.6%) on the left.ConclusionsIn dynamic imaging of the TMJ, qualitative assessment of condyle-disc movement and joint effusion is minimally dependent on the reader’s evaluation. Measurement of the condylar pathway shows an interobserver variability of ±30%.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la variabilità inter-osservatore della risonanza magnetica (RM) dinamica dell’articolazione temporo-mandibolare (ATM).Materiali e metodiSessantadue pazienti con disfunzione condilo-meniscale (124 ATM) sono stati studiati con tecnica RM dinamica dell’ATM su apparecchio da 1,5 T durante movimento fisiologico di apertura e chiusura buccale. Due lettori hanno valutato indipendentemente la qualità dell’esame (Q: non diagnostico, diagnostico, ottimale), il movimento condilare (MC: limitato, subottimale, ottimale), l’orientamento condilare (OC: nel piano, fuori dal piano), visibilità e movimento del disco (VD: visibile, non visibile; M: normale, dislocazione ridotta, dislocazione non ridotta) e il fluido articolare (F: presente, assente). Per ogni ATM, è stato inoltre misurato il percorso condilare demarcando la posizione del condilo nei frame dell’acquisizione dinamica. È stata stimata la concordanza tra i due osservatori (κ di Cohen, Bland-Altman).RisultatiLa concordanza è risultata ottimale per Q (non diagnostico, diagnostico, ottimale: 0,8%, 4,9%, 94,3%; κ=1), MC (limitato, subottimale, ottimale: 14%, 26,4%, 59,5%; κ=0,84) e VD (visibile, non visibile: 100%, 0%), buona per M (normale, dislocazione riducibile, non riducibile: 66,1%, 14,8%, 19,1%; κ=0,64) e V (presente, assente: 41,3%, 58,7%; κ=0,67), moderata per OC (nel piano, fuori dal piano: 94,2%, 5,8%; κ=0,41). Per il percorso condilare, la media delle differenze percentualizzate ed i limiti di concordanza (LC) sono risultati −3%, (LC: −34,5%, 28,3%) a destra e −1,2% (LC: −35%, 32,6%) a sinistra.ConclusioniLa valutazione qualitativa del movimento condilo-meniscale e della presenza di fluido intraarticolare nell’imaging dinamico dell’ATM è solo minimamente dipendente dalla stima dell’osservatore, mentre la misurazione del tracciato condilare presenta una variabilità inter-osservatore pari a ±30%.