Effect of zirconium oxide and zinc oxide nanoparticles on physicochemical properties and antibiofilm activity of a calcium silicate-based material

The aim of the present study was to evaluate the antibiofilm activity against Enterococcus faecalis, compressive strength. and radiopacity of Portland cement (PC) added to zirconium oxide (ZrO2), as radiopacifier, with or without nanoparticulated zinc oxide (ZnO).The following experimental materials were evaluated: PC, PC + ZrO2, PC + ZrO2 + ZnO (5%), and PC + ZrO2 + ZnO (10%). Antibiofilm activity was analyzed by using direct contact test (DCT) on Enterococcus faecalis biofilm, for 5 h or 15 h. The analysis was conducted by using the number of colony-forming units (CFU/mL). The compressive strength was performed in a mechanical testing machine. For the radiopacity tests, the specimens were radiographed together with an aluminium stepwedge. The results were submitted to ANOVA and Tukey tests, with level of significance at 5%. The results showed that all materials presented similar antibiofilm activity (

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.

Polycaprolactone fibres as a potential delivery system for collagen to support bone regeneration

Poly(e-caprolactone) (PCL) is biocompatible, non-immunogenic and non-toxic, and slowly degrades, allowing sufficient time for tissue regeneration. PCL has the potential for application in bone and cartilage repair as it may provide the essential structure required for bone regeneration, however, an ideal scaffold system is still undeveloped. PCL fibres were prepared using the gravity spinning technique, in which collagen was either incorporated into or coated onto the 'as-spun' fibres, in order to develop novel biodegradable polymer fibres which will effectively deliver collagen and support the attachment and proliferation of human osteoblast (HOB) cells for bone regeneration. The physical and mechanical characteristics and cell fibre interactions were analysed. The PCL fibres were found to be highly flexible and inclusion of collagen did not alter the mechanical properties of PCL fibres. Overall, HOB cells were shown to effectively adhere and proliferate on all fibre platforms tested, although proliferation rates were enhanced by surface coating PCL fibres with collagen compared to PCL fibres incorporating collagen and PCL-only fibres. These findings highlight the potential of using gravity spun PCL fibres as a delivery platform for extracellular matrix proteins, such as collagen, in order to enhance cell adherence and proliferation for tissue repair.

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically

Toward biomimetic materials in bone regeneration : functional behavior of mesenchymal stem cells on a broad spectrum of extracellular matrix components

Bone defect treatments can be augmented by mesenchymal stem cell (MSC) based therapies. MSC interaction with the extracellular matrix (ECM) of the surrounding tissue regulates their functional behavior. Understanding of these specific regulatory mechanisms is essential for the therapeutic stimulation of MSC in vivo. However, these interactions are presently only partially understood. This study examined in parallel, for the first time, the effects on the functional behavior of MSCs of 13 ECM components from bone, cartilage and hematoma compared to a control protein, and hence draws conclusions for rational biomaterial design. ECM components specifically modulated MSC adhesion, migration, proliferation, and osteogenic differentiation, for example, fibronectin facilitated migration, adhesion, and proliferation, but not osteogenic differentiation, whereas fibrinogen enhanced adhesion and proliferation, but not migration. Subsequently, the integrin expression pattern of MSCs was determined and related to the cell behavior on specific ECM components. Finally, on this basis, peptide sequences are reported for the potential stimulation of MSC functions. Based on the results of this study, ECM component coatings could be designed to specifically guide cell functions.

A bi-lineage conducive scaffold for osteochondral defect regeneration

Because cartilage and bone tissues have different lineage-specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium-containing mesoporous bioglass (Li-MBG) scaffold is developed. The efficacy and mechanism of Li-MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro-CT results show that Li-MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage-like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li-MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi-lineage conducive scaffolds that enhance regeneration of osteochondral defects.

Bone regeneration based on tissue engineering conceptions – a 21st century perspective

The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~ 100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity.

Effect of calcium deficiency on the mechanical properties of hydroxyapatite crystals

The deterioration of the mechanical properties of bone with age is related to several factors including the structure, organization and chemistry of the constituent phases; however, the relative contribution of each of these factors is not well understood. In this study, we have investigated the effect of chemistry (calcium deficiency) on the mechanical properties of single crystals of hydroxyapatite. Single crystals of stoichiometric crystals grown by the flux method and calcium-deficient platelet crystals grown using wet chemical methods were used as model systems. Using nanoindentation, we show that calcium deficiency leads to an 80% reduction in the hardness and elastic modulus and at least a 75% reduction in toughness in plate-shaped hydroxyapatite crystals. Measurement of local mechanical properties using nanoindentation and nanoscale chemistry through elemental mapping in a transmission electron microscope points to a direct correlation between the observed spatial variation in composition and the large scatter in the measured hardness and modulus values. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

Objectives: A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1-RHLI positive control, 2-RHLI plus ZOL (50 mu g/kg, i.v. single dose), 3-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week), 4-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week) plus ZOL (50 mu g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats. Conclusions: These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

The spectroscopic properties of Er3(+)-doped TeO2-Nb2O5 glasses with high mechanical strength performance

(100 - x)TeO2 - xNb(2)O(5) (x=5-20) mobic tellurite glasses doped with 0.5 mol.% Er2O3 were synthesized, and their thermal, mechanical, and spectroscopic properties were measured and compared to the properties of the typical 75TeO(2)-20ZnO-5Na(2)O (TZN) tellurite glass. The refractive index (n(d)), density (p), and glass transition temperature (T-g) of bulk glasses increase with the Nb2O5 content. The Vickers microhardness (H-v) of bulk glass in niobic tellurite glasses also increases with the Nb2O5 content. The values (2.5-3.2 GPa) of H, in the niobic tellurite glasses are 47-88% larger than that (1.7 GPa) in TZN glass. The effect of Nb2O5 content on absorption spectra, the Judd-Ofelt parameters Omega(t) (t = 2, 4, 6), fluorescence spectra and the lifetimes of Er3+ :I-13/2 level were also investigated, and the stimulated emission crosssection was calculated from McCumber theory. With increasing Nb2O5 content in the glass composition, the Omega(t) (t = 2, 4, 6) parameters, fluorescence full width at half maximum (FWHM) Of I-13/2 of Er3+ increase, while the I-4(13/2) lifetimes of Er3+ decreases. Compared with TZN glass, the gain bandwidth properties of Er3+-doped TeO2-Nb2O5 glass is much larger than in tellurite glass based TeO2-ZnO-Na2O system, bismush-based glass, germanate, and silicate glasses, which indicates that TeO2-Nb2O5 glasses are better choice as a practical available host material for broadband Er3+-doped amplifier. (c) 2005 Elsevier B.V. All rights reserved.

Allogenic Peripheral Blood Derived Mesenchymal Stem Cells (MSCs) Enhance Bone Regeneration in Rabbit Ulna Critical-Sized Bone Defect Model

Mesenchymal stem cells (MSCs) were demonstrated to exist within peripheral blood (PB) of several mammalian species including human, guinea pig, mice, rat, and rabbit. Whether or not the PB derived MSCs (PBMSCs) could enhance the regeneration of large bone defects have not been reported. In this study, rabbit MSCs were obtained from mononuclear cells (MNCs) cultures of both the PB and bone marrow (BM) origin. The number of PBMSCs was relatively lower, with the colony forming efficiency (CFE) ranging from 1.2-13 per million MNCs. Under specific inductive conditions, PBMSCs differentiated into osteoblasts, chondrocytes, and adipocytes, showing multi- differentiation ability similar to BMMSCs. Bilateral 20 mm critical-sized bone defects were created in the ulnae of twelve 6-month old New Zealand white rabbits. The defects were treated with allogenic PBMSCs/Skelite (porous calcium phosphate resorbable substitute), BMMSCs/Skelite, PBMNCs/Skelite, Skelite alone and left empty for 12 weeks. Bone regeneration was evaluated by serial radiography, peripheral quantitative computed tomography (pQCT), and histological examinations. The x-ray scores and the pQCT total bone mineral density in the PBMSCs/Skelite and BMMSCs/Skelite treated groups were significantly greater than those of the PBMNCs/Skelite and Skelite alone groups (p