A comparative in vivo evaluation of bioactive glasses and bioactive glass-based composites for bone tissue repair

In this work a set of novel materials for bone tissue regeneration have been tested in vivo in an animal model. In fact, despite many studies have been devoted to amorphous 45S5 Bioglass®, there is lack in the literature of works aimed to study the in vivo performance of heat-treated – and thus partially crystallized – 45S5. As widely reported, crystallization limits the bioactivity of 45S5 and is the main reason that prevents a broader use of this material. Thus, in the present work, a recently developed bioactive glass (BG_Ca/Mix) is tested, since previous investigations demonstrated that BG_Ca/Mix is particularly promising by virtue of both its high bioactivity and lower tendency to crystallize with respect to 45S5. BG_Ca/Mix sintered powders and two composites, which contain BG_Ca/Mix and an increasing percentage (20 wt% or 70 wt%) of hydroxyapatite (HA), were considered. As a term of comparison, 45S5 sintered powders were also studied. The samples were implanted in rabbits' femurs and harvested after 8 weeks. The histological analysis demonstrated that BG_Ca/Mix has an osteoconductive ability slightly higher than that of 45S5 glass-ceramics, followed by that of the composites, which may represent the starting point for obtaining systems with degradation rate tailored for a given clinical application. Moreover, the 45S5 samples were locally cracked, probably because of a non-uniform dissolution in the physiological environment. On the contrary such cracks, which could lead to implant instability and unsuitable mechanical performance, were not observed in BG_Ca/Mix

Cell Proliferation to Evaluate Preliminarily the Presence of Enduring Self-Regenerative Antioxidant Activity in Cerium Doped Bioactive Glasses

(1) Background: a cell evaluation focused to verify the self-regenerative antioxidant activity is performed on cerium doped bioactive glasses. (2) Methods: the glasses based on 45S5 Bioglass®, are doped with 1.2 mol%, 3.6 mol% and 5.3 mol% of CeO2 and possess a polyhedral shape (~500 µm2). Glasses with this composition inhibit oxidative stress by mimicking catalase enzyme (CAT) and superoxide dismutase (SOD) activities; moreover, our previous cytocompatibility tests (neutral red (NR), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Bromo-2-deoxyUridine (BrdU)) reveal that the presence of cerium promotes the absorption and vitality of the cells. The same cytocompatibility tests were performed and repeated, in two different periods (named first and second use), separated from each other by four months. (3) Results: in the first and second use, NR tests indicate that the presence of cerium promotes once again cell uptake and viability, especially after 72 h. A decrease in cell proliferation it is observed after MTT and BrdU tests only in the second use. These findings are supported by statistically significant results (4) Conclusions: these glasses show enhanced proliferation, both in the short and in the long term, and for the first time such large dimensions are studied for this kind of study. A future prospective is the implantation of these bioactive glasses as bone substitute in animal models

PRELIMINARY FINDINGS OF A POTENZIATED PIEZOSURGERGICAL DEVICE AT THE RABBIT SKULL

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery

Sol-gel derived bioactive glasses with low tendency to crystallize: synthesis, post-sintering bioactivity and possible application for the production of porous scaffolds.

A new sol-gel (SG) method is proposed to produce special bioactive glasses (BG_Ca family) characterized by a low tendency to devitrify. These formulations, derived from 45S5 Bioglass®, are characterized by a high content of CaO (45.6 mol%) and by a partial or complete substitution of sodium oxide with potassium oxide (total amount of alkaline oxides: 4.6 mol%), which increases the crystallization temperature up to 900°C. In this way, it is possible to produce them by SG preserving their amorphous nature, in spite of the calcination at 850°C. The sintering behavior of the obtained SG powders is thoroughly investigated and the properties of the sintered bodies are compared to those of the melt-derived (M) counterparts. Furthermore, the SG glass powders are successfully used to produce scaffolds by means of a modified replication technique based on the combined use of polyurethane sponges and polyethylene particles. Finally, in the view of a potential application for bone tissue engineering, the cytotoxicity of the produced materials is evaluated in vitro

Bone regeneration by novel bioactive glasses containing strontium and/or magnesium: A preliminary in-vivo study

In this work, a set of novel bioactive glasses have been tested in vivo in an animal model. The new compositions, characterized by an exceptional thermal stability and high in vitro bioactivity, contain strontium and/or magnesium, whose biological benefits are well documented in the literature. To simulate a long-term implant and to study the effect of the complete dissolution of glasses, samples were implanted in the mid-shaft of rabbits' femur and analyzed 60 days after the surgery; such samples were in undersized powder form. The statistical significance with respect to the type of bioactive glass was analyzed by Kruskal-Wallis test. The results show high levels of bone remodeling, several new bone formations containing granules of calcium phosphate (sometimes with amounts of strontium and/or magnesium), and the absence of adverse effects on bone processes due to the almost complete glass dissolution. In vivo results confirming the cell culture outcomes of a previous study highlighted that these novel bioglasses had osteostimulative effect without adverse skeletal reaction, thus indicating possible beneficial effects on bone formation processes. The presence of strontium in the glasses seems to be particularly interesting

A microbiological and morphological study of blocked biliary stents

Biliary stent blockage represents the main limitation of the use of such devices in relieving obstructive jaundice due to a variety of malignant and benign conditions. Microbiological and morphological analysis of the occluding sludge present on the inner surface of 30 biliary stents was performed to evaluate the different components of such material and the effect of the antibiotic treatment on the biofilm formation. A highly organized biofilm, constituted by microbial cells embedded in an amorphous matrix together with crystallized bile salts, was observed Enterococcus spp . represented the most common isolate from both occluded and non-occluded stents. The antibiotic therapy, while selecting for multi-resistant bacteria and fungi, might possibly delay the biofilm formation. Key words: biliary stents, microbial colonization, biofilm

Pulsed Electro-Magnetic Field (PEMF) Effect on Bone Healing in Animal Models: A Review of Its Efficacy Related to Different Type of Damage

Biophysical energies are a versatile tool to stimulate tissues by generating biopotentials. In particular, pulsed electromagnetic field (PEMF) stimulation has intrigued researchers since the 1970s. To date, many investigations have been carried out in vivo, but a gold standard treatment protocol has not yet been defined. The main obstacles are represented by the complex setting of PEMF characteristics, the variety of animal models (including direct and indirect bone damage) and the lack of a complete understanding of the molecular pathways involved. In the present review the main studies about PEMF stimulation in animal models with bone impairment were reviewed. PEMF signal characteristics were investigated, as well as their effect on molecular pathways and osseous morphological features. We believe that this review might be a useful starting point for a prospective study in a clinical setting. Consistent evidence from the literature suggests a potential beneficial role of PEMF in clinical practice. Nevertheless, the wide variability of selected parameters (frequency, duration, and amplitude) and the heterogeneity of applied protocols make it difficult to draw certain conclusions about PEMF effectiveness in clinical implementation to promote bone healing. Deepening the knowledge regarding the most consistent results reported in literature to date, we believe that this review may be a useful starting point to propose standardized experimental guidelines. This might provide a solid base for further controlled trials, to investigate PEMF efficacy in bone damage conditions during routine clinical practic

Bone Healing Evaluation Following Different Osteotomic Techniques in Animal Models: A Suitable Method for Clinical Insights

Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings