Effect of nano-hydroxyapatite and ozone on approximal initial caries: a randomized clinical trial.

The aim of the study was to assess the efficacy of three methods of enamel remineralization on initial approximal caries: (1) a nano-hydroxyapatite gel, (2) gaseous ozone therapy, (3) combination of a nano-hydroxyapatite gel and ozone. Patients (n = 92, age 20-30 years) with initial approximal enamel lesions on premolar and molar teeth (n = 546) were randomly allocated to three groups subjected to a 6-months treatment: Group I: domestic nano-hydroxyapatite remineralizing gel, group II: in-office ozone therapy, group III: both domestic remineralizing gel and ozone therapy. Caries lesions were assessed on bitewing radiographs at baseline, after 1 year and after 2 years. At one-year follow-up, the smallest rate of lesions with remineralisation (36.5%) was found in group I, and the highest (69.3%)-in group III. In group III a significant remineralisation was noticed in after 1 year and then a demineralisation after 2 years. Thus nano-hydroxyapatite gel and ozone therapy exert some capacities to remineralize approximal enamel and dentine subsurface lesions of premolar and molar teeth. Moreover, the combination of both methods produces the best effect compared to nano-hydroxyapatite or ozone therapy applied alone. However, the treatment should be continued for a long time in order to achieve nonrestorative recovery of caries.

Nano-hydroxyapatite use in dentistry: a systematic review.

Nano-hydroxyapatite (nano-HA) is a material with multiple uses due to its biocompatibility and its resemblance to the nonorganic bone structure. It is used in various dental domains such as implantology, surgery, periodontology, esthetics and prevention. The aim of this study is to provide a wide understanding of nano-HA and to promote treatments based on nanomaterials in dentistry. A search in two data bases, Scopus, and PubMED, was conducted over a 5 years period. We chose a 5 years period because this revealed the most recent published studies with the key words 'nano-HA' and 'dentistry'. A number of 32 studies were included in this systematic review. In implantology the main use of nano-HA was as a coating material for titanium implants and its effect was assessed in the matter of osteointegration and inflammatory response as well as antibacterial activity. In tissue engineering the use of nano-HA was directed to surgery and periodontology and this material was assessed mainly as a grafting material. In esthetics and prevention its use was mainly focused on dentinal hypersensitivity treatment, remineralizing potential and as bleaching co-agent. Nano-HA is a relatively novel material with outstanding physical, chemical, mechanical and biological properties that makes it suitable for multiple interventions. It outperformed most of the classic materials used in implantology and surgery but it should be further investigated for bone engineering and caries prevention therapy.

A bioceramic scaffold composed of strontium-doped three-dimensional hydroxyapatite whiskers for enhanced bone regeneration in osteoporotic defects.

Reconstruction of osteoporotic bone defects is a clinical problem that continues to inspire the design of new materials. Methods: In this work, bioceramics composed of strontium (Sr)-doped hydroxyapatite (HA) whiskers or pure HA whiskers were successfully fabricated by hydrothermal treatment and respectively named SrWCP and WCP. Both bioceramics had similar three-dimensional (3D) porous structures and mechanical strengths, but the SrWCP bioceramic was capable of releasing Sr under physiological conditions. In an osteoporotic rat metaphyseal femoral bone defect model, both bioceramic scaffolds were implanted, and another group that received WCP plus strontium ranelate drug administration (Sr-Ran+WCP) was studied for comparison. Results: At week 1 post-implantation, osteogenesis coupled blood vessels were found to be more common in the SrWCP and Sr-Ran+WCP groups, with substantial vascular-like structures. After 12 weeks of implantation, comparable to the Sr-Ran+WCP group, the SrWCP group showed induction of more new bone formation within the defect as well as at the implant-bone gap region than that of the WCP group. Both the SrWCP and Sr-Ran+WCP groups yielded a beneficial effect on the surrounding trabecular bone microstructure to resist osteoporosis-induced progressive bone loss. While an abnormally high blood Sr ion concentration was found in the Sr-Ran+WCP group, SrWCP showed little adverse effect. Conclusion: Our results collectively suggest that the SrWCP bioceramic can be a safe bone substitute for the treatment of osteoporotic bone defects, as it promotes local bone regeneration and implant osseointegration to a level that strontium ranelate can achieve.

Nanohydroxyapatite Based Ceramic Carrier Promotes Bone Formation in a Femoral Neck Canal Defect in Osteoporotic Rats.

Hip fractures are among the most common types of fracture risks in old age osteoporotic patients that often end up with immobile disabilities. Weak bones due to loss of mineral content along with an increase in the porosity of the femur neck canal in osteoporosis reduce the mechanical properties of the bone and predispose the patients to fractures. In this study, we have used calcium sulfate/nanohydroxyapatite based nanocement (NC) as carrier of recombinant human bone morphogenetic protein-2 (BMP-2), zoledronate (ZA), and bone marrow mesenchymal stromal cells (MSCs) derived exosomes (EXO) to enhance bone formation and defect healing in a femur neck canal defect model in osteoporotic rats. A cylindrical defect in the femur neck canal with dimensions of 1 mm (diameter) × 8 mm (length) starting from the lateral cortex toward the apex of the femur head was developed. The defect was impacted using NC alone or functionalized as (a) NC + ZA (systemic), (b) NC + ZA (local), (c) NC + EXO + ZA, and (d) NC + BMP + ZA to evaluate bone formation by ex vivo micro-computed tomography (micro-CT) and histological analysis 16 weeks postsurgery. Moreover, the femurs (both defect and contralateral leg) were subjected to biomechanical analysis to assess the effect of treatments on compressive mechanical properties of the bones. The treatment groups (NC + ZA (L), NC + BMP + ZA, and NC + EXO + ZA) showed enhanced bone formation with complete healing of the defect. No differences in the mechanical properties of both the defect and contralateral across the leg were observed among the groups. However, a trend was observed where NC + BMP + ZA showed enhanced biomechanical strength in the defect leg. This suggests that NC could act as a potent carrier of bioactive molecules to reduce the risks of hip fractures in osteoporotic animals. This type of treatment can be given to patients who are at higher risk of osteoporosis mediated femur neck fracture as a preventive measure or for enhanced healing in already compromised situations. Moreover, this study provided a proof of concept regarding the use of exosomes in bone regeneration therapy, which might be used as a booster dose that will eventually reduce the dosage of BMP and hence circumvent the limitations associated with the use of BMP.

Improved Healing by Adjuvant Osteoconductive Therapy Using a Novel Cotton-Like Hydroxyapatite Sheet After Median Sternotomy.

The union rate of wire fixation after median sternotomy remains unsatisfactory. We developed a novel osteoconductive sheet composed of hydrophilized hydroxyapatite and evaluated its osteogenetic effect when interposed between sternal halves in a canine model. Eighteen canines were divided equally into groups based on the hemostatic agent used: osteoconductive sheet (S), none (C), and bone wax (BW). After median sternotomy, the sternal halves were closed by wire fixation. In each group, 3 canines were euthanized at 1 month, while 3 were euthanized at 2 months. Resected sternums were mechanically assessed by the 3-point bending test, radiographically assessed by micro-CT, and pathologically assessed to quantify the osteogenesis between sternal halves. Compared with the BW group, the S group had a greater maximum stress at 1 month (S: 322.9 ± 107.7 N, C: 233.0 ± 62.7 N, BW: 124.9 ± 88.4 N; P = 0.025), and greater maximum shear force at 1 month (S: 1.92 ± 0.67 N/m2; C: 1.23 ± 0.28 N/m2; BW: 0.68 ± 0.41 N/m2; P = 0.025). Micro-CT revealed that the S group had more osteogenesis than the BW group at 1 month (25.7% ± 9.8% vs 6.9% ± 9.2%), and 2 months (34.0% ± 15.1% vs 14.8% ± 9.4%); the respective values in the C group were 17.1% ± 7.2% and 29.7% ± 9.3%. Pathologic examination revealed that the S group had the greatest osteogenetic area at 2 months (S: 38.8% ± 18.8%; C: 24.5% ± 6.9%; BW: 24.7% ± 18.6%). Adjuvant osteoconductive therapy using a cotton-like hydroxyapatite sheet in addition to wire fixation significantly improved sternal healing compared with BW. This new material also showed relatively better outcome than the C group.

Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo.

Incorporating a biomimetic coating and integrating osteoinductive biomolecules into basic bone substitutes are two common strategies to improve osteogenic capabilities in bone tissue engineering. Currently, the underlying mechanism of osteoporosis (OP)-related deficiency of osteogenesis remains unclear, and few treatments target at OP-related bone regeneration. Herein, we describe a self-assembling polyelectrolyte multilayered (PEM) film coating with local immobilisation of calcitriol (Cal) in biphasic calcium phosphate (BCP) scaffolds to promote osteoporotic bone regeneration by targeting the calcium sensing receptor (CaSR). Methods: The ovariectomy-induced functional changes in bone marrow mesenchymal stem cells (BMSCs), protective effects of Cal, and the potential mechanism were all verified. A PEM film composed of hyaluronic acid (HA) and chitosan (Chi) was prepared through layer-by-layer self-assembly. The morphology, growth behaviour, and drug retention capability of the composite scaffolds were characterised, and their biocompatibility and therapeutic efficacy for bone regeneration were systematically explored in vitro and in vivo.Results: The osteogenic differentiation, adhesion, and proliferation abilities of ovariectomised rat BMSCs (OVX-rBMSCs) decreased, in accordance with the deficiency of CaSR. Cal effectively activated osteogenesis in these OVX-rBMSCs by binding specifically to the active pocket of the CaSR structure, while the biomimetic PEM coating augmented OVX-rBMSCs proliferation and adhesion due to its porous surface structure. The PEM-coated scaffolds showed advantages in Cal loading and retention, especially at lower drug concentrations. HA/Chi PEM synergised with Cal to improve the proliferation, adhesion, and osteogenesis of OVX-rBMSCs and promote bone regeneration and BCP degradation in the critical-size calvarial bone defect model of OVX rats. Conclusion: A composite scaffold based on BCP, created by simply combining a biomimetic PEM coating and Cal immobilisation, could be clinically useful and has marked advantages as a targeted, off-the-shelf, cell-free treatment option for osteoporotic bone regeneration.

A Comparative Study with Biphasic Calcium Phosphate to Deproteinized Bovine Bone in Maxillary Sinus Augmentation: A Prospective Randomized and Controlled Clinical Trial.

PURPOSE: The purpose of this study was to evaluate a new graft material, biphasic calcium phosphate, composed of 60% hydroxyapatite and 40% ß-Tricalcium phosphate and deproteinized bovine bone mineral, which is established as a predictable graft material for maxillary sinus augmentation. MATERIALS AND METHODS: Maxillary sinus augmentation was performed with different bone materials. Bone biopsies were performed on tissue harvested from the future implant bed using a trephine bur at 6 months after maxillary sinus augmentation. Resonance frequency analysis was performed immediately and at 6 months after the implant placement. Microcomputed tomography and histomorphometric analysis were performed in all patients. RESULTS: Fifty-six patients (60 sinuses) were included in the study. At 6 months postoperative, 31 biopsies were performed on tissues harvested from the calcium phosphate, and 29 biopsies on tissues from the bovine bone grafts. There was no implant failure during the 21-month mean follow-up period. The overall implant stability quotient values were higher than 60, and gradually increased for 6 months. Higher new bone volume fraction and new bone surface density were observed in the calcium phosphate group compared with the bovine bone group. In contrast, residual bone graft volume in the bovine bone group was higher than that in the calcium phosphate group. Nevertheless, there was no significant difference between groups in the microcomputed tomography and histomorphometric parameters. CONCLUSION: Within the study's limitations, both graft materials demonstrated similar biocompatibility and osteoconductivity in the maxillary sinus augmentation.

The synergistic effect of strontium-substituted hydroxyapatite and microRNA-21 on improving bone remodeling and osseointegration.

Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. As the population ages, improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Herein, we fabricated a titanium (Ti)-based SrHA/miR-21 composite coating that was generated by hydrothermal deposition of SrHA followed by miR-21 nanocapsule immobilisation. Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of Ti. In vitro experiments revealed that the composite coating was beneficial for osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of the angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength. Therefore, this method provides a new strategy for bone repair.

Injectable TEMPO-oxidized nanofibrillated cellulose/biphasic calcium phosphate hydrogel for bone regeneration.

Nanofibrillated cellulose, obtained from rice straw agricultural wastes was used as a substrate for the preparation of a new injectable and mineralized hydrogel for bone regeneration. Tetramethyl pyridine oxyl (TEMPO) oxidized nanofibrillated cellulose, was mineralized through the incorporation of a prepared and characterized biphasic calcium phosphate at a fixed ratio of 50 wt%. The TEMPO-oxidized rice straw nanofibrillated cellulose was characterized using transmission electron microscopy, Fourier transform infrared, and carboxylic content determination. The injectability and viscosity of the prepared hydrogel were evaluated using universal testing machine and rheometer testing, respectively. Cytotoxicity and alkaline phosphatase level tests on osteoblast like-cells for in vitro assessment of the biocompatibility were investigated. Results revealed that the isolated rice straw nanofibrillated cellulose is a nanocomposite of the cellulose nanofibers and silica nanoparticles. Rheological properties of the tested materials are suitable for use as injectable material and of nontoxic effect on osteoblast-like cells, as revealed by the positive alkaline phosphate assay. However, nanofibrillated cellulose/ biphasic calcium phosphate hydrogel showed higher cytotoxicity and lower bioactivity test results when compared to that of nanofibrillated cellulose.

Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat.

OBJECTIVES: To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model. MATERIAL AND METHODS: The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-µl single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks. RESULTS: The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM-0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05). CONCLUSIONS: When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive manner.

The Influences of Different Ratios of Biphasic Calcium Phosphate and Collagen Augmentation on Posterior Lumbar Spinal Fusion in Rat Model.

PURPOSE: To determine the influence of different ratios of hydroxyapatite (HA)/beta tricalcium phosphate (ß-TCP) and collagen augmentation for posterior lumbar fusion in a rat model. MATERIALS AND METHODS: We generated a posterior lumbar fusion model in 50 rats and divided it into five groups of equal number as follows; 1) autologous bone graft as group A, 2) 70% HA+30% ß-TCP as group B, 3) 70% HA+30% ß-TCP+collagen as group C, 4) 30% HA+70% ß-TCP as group D, and 5) 30% HA+70% ß-TCP+collagen as group E. Rats were euthanized at 12 weeks after surgery and fusion was assessed by manual palpation, quantitative analysis using microCT and histology. RESULTS: The score of manual palpation was significantly higher in group C than group E (3.1±1.1 vs. 1.8±0.8, p=0.033). However, in terms of microCT analysis, group D showed significantly higher scores than group B (5.5±0.8 vs. 3.1±1.1, p=0.021). According to quantitative volumetric analysis, 30% HA+70% ß-TCP groups (group D and E) showed significantly reduced fusion mass at 12 weeks after surgery (123±14.2, 117±46.3 vs. 151±27.3, p=0.008, 0.003, respectively). Collagen augmentation groups revealed superior results in terms of both microCT score and histologic grade. CONCLUSION: A 7:3 HA/ß-TCP ratio with collagen augmentation rather than a 3:7 HA/ß-TCP ratio could be a more favorable graft substitute for lumbar spinal fusion. There was positive role of collagen as an adjunct for spinal bone fusion process.

Treatment of Non-Contained Infrabony Defects With Enamel Matrix Derivative Alone or in Combination With Biphasic Calcium Phosphate Bone Graft: A 12-Month Randomized Controlled Clinical Trial.

BACKGROUND: Use of enamel matrix derivative (EMD) when dealing with non-contained defects may be limited because EMD does not maintain a space itself. Use of combined therapy has been proposed, using a bone graft in combination with EMD to avoid collapse of the flap into the bony defect during healing time. Therefore, the aim of this study is to evaluate the clinical and radiologic healing response of non-contained infrabony defects after treatment with a combination of EMD and biphasic calcium phosphate (BC) or EMD alone. METHODS: Fifty-two patients with at least one infrabony defect ≥3 mm in depth with a probing depth (PD) ≥6 mm were randomly treated with EMD/BC or EMD alone. Clinical and radiographic parameters were evaluated at baseline, 6, and 12 months after surgery. To standardize the procedure, an acrylic stent and millimeter radiographic grid were used. The primary outcome was the change in clinical attachment level (CAL). RESULTS: Analysis of the data demonstrated a statistically significant difference from baseline within each group (P <0.05), with a difference in clinical and radiographic parameters at 6 and 12 months. After 1 year, mean PD reductions of 3.14 ± 1.95 mm (39.6%) in the EMD/BC group and 3.30 ± 1.89 mm (48.7%) in the EMD group were achieved. A mean CAL gain of 2.38 ± 2.17 mm (24.9%) in the EMD/BC group and 2.65 ± 2.18 mm (36.2%) in the EMD group were obtained. Reduction in the infrabony component was 2.71 ± 1.79 mm (57.9%) in the test group and 2.60 ± 2.03 mm (28.5%) in the control group. There were no statistically significant differences between treatment groups. CONCLUSIONS: It was concluded that treatment of non-contained infrabony defects with EMD, with or without BC, resulted in statistically significantly better results after 12 months compared with baseline measurements. In contrast, the combined approach did not result in a statistically significant improvement.

Quantitative Kinetics Evaluation of Blocks Versus Granules of Biphasic Calcium Phosphate Scaffolds (HA/ß-TCP 30/70) by Synchrotron Radiation X-ray Microtomography: A Human Study.

INTRODUCTION: Successful bone regeneration using both granules and blocks of biphasic calcium phosphate materials has been reported in the recent literature, in some clinical applications for maxillary sinus elevation, but the long-term kinetics of bone regeneration has still not been fully investigated. MATERIALS AND METHODS: Twenty-four bilateral sinus augmentation procedures were performed and grafted with hydroxyapatite/ß-tricalcium phosphate 30/70, 12 with granules and 12 with blocks. The samples were retrieved at different time points and were evaluated for bone regeneration, graft resorption, neovascularization, and morphometric parameters by computed microtomography and histology. RESULTS: A large amount of newly formed bone was detected in the retrieved specimens, together with a good rate of biomaterial resorption and the formation of a homogeneous and rich net of new vessels. The morphometric values were comparable at 5/6 months from grafting but, 9 months after grafting, revealed that the block-based specimens mimicked slightly better than granule-based samples the healthy native bone of the maxillary site. CONCLUSION: The scaffold morphology was confirmed to influence the long-term kinetics of bone regeneration.

A high concentration of recombinant human bone morphogenetic protein-2 induces low-efficacy bone regeneration in sinus augmentation: a histomorphometric analysis in rabbits.

OBJECTIVES: The aim of the study was to elucidate the efficacy of bone regeneration at the early stage of healing in rabbit sinuses grafted with a biphasic calcium phosphate (BCP) carrier soaked in a high concentration of recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: Both maxillary sinuses of eight male rabbits were used. The sinus on one side (assigned randomly) was grafted with BCP loaded with rhBMP-2 (1.5 mg/ml; test group) using a soaking method, while the other was grafted with saline-soaked BCP (control group). After a 2-week healing period, the sinuses were analyzed by micro-computed tomography and histomorphometry. RESULTS: The total augmented area and soft tissue space were significantly larger in the test group than in the control group, whereas the opposite was true for the area of residual material and newly formed bone. Most of the new bone in the test group was localized to the Schneiderian membrane (SM), while very little bone formation was observed in the window and center regions of the sinus. New bone was distributed evenly in the control group sinuses. CONCLUSION: Within the limitations of this study, it appeared that application of a high concentration of rhBMP-2 soaked onto a BCP carrier inhibited bone regeneration from the pristine bone and increased soft tissue swelling and inflammatory response at the early healing stage of sinus augmentation, although osteoinductive potential was found along the SM.

Benefits of biphasic calcium phosphate hybrid scaffold-driven osteogenic differentiation of mesenchymal stem cells through upregulated leptin receptor expression.

BACKGROUND: The use of mesenchymal stem cells (MSCs) and coralline hydroxyapatite (HA) or biphasic calcium phosphate (BCP) as a bone substitute for posterolateral spinal fusion has been reported. However, the genes and molecular signals by which MSCs interact with their surrounding environment require further elucidation. METHODS: MSCs were harvested from bone grafting patients and identified by flow cytometry. A composite scaffold was developed using poly(lactide-co-glycolide) (PLGA) copolymer, coralline HA, BCP, and collagen as a carrier matrix for MSCs. The gene expression profiles of MSCs cultured in the scaffolds were measured by microarrays. The alkaline phosphatase (ALP) activity of the MSCs was assessed, and the expression of osteogenic genes and proteins was determined by quantitative polymerase chain reaction (Q-PCR) and Western blotting. Furthermore, we cultured rabbit MSCs in BCP or coralline HA hybrid scaffolds and transplanted these mixtures into rabbits for spinal fusion. We investigated the differences between BCP and coralline HA hybrid scaffolds by dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT). RESULTS: Tested in vitro, the cells were negative for hematopoietic cell markers and positive for MSC markers. There was higher expression of 80 genes and lower of 101 genes of MSCs cultured in BCP hybrid scaffolds. Some of these genes have been shown to play a role in osteogenesis of MSCs. In addition, MSCs cultured in BCP hybrid scaffolds produced more messenger RNA (mRNA) for osteopontin, osteocalcin, Runx2, and leptin receptor (leptin-R) than those cultured in coralline HA hybrid scaffolds. Western blotting showed more Runx2 and leptin-R protein expression in BCP hybrid scaffolds. For in vivo results, 3D reconstructed CT images showed continuous bone bridges and fusion mass incorporated with the transverse processes. Bone mineral content (BMC) values were higher in the BCP hybrid scaffold group than in the coralline HA hybrid scaffold group. CONCLUSIONS: The BCP hybrid scaffold for osteogenesis of MSCs is better than the coralline HA hybrid scaffold by upregulating expression of leptin-R. This was consistent with in vivo data, which indicated that BCP hybrid scaffolds induced more bone formation in a spinal fusion model.

Effect of Local Sustainable Release of BMP2-VEGF from Nano-Cellulose Loaded in Sponge Biphasic Calcium Phosphate on Bone Regeneration.

Bone regeneration is a coordinated process mainly regulated by multiple growth factors. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and bone morphogenetic proteins (BMPs) induce osteogenesis during bone healing process. The aim of this study was to investigate how these growth factors released locally and sustainably from nano-cellulose (NC) simultaneously effect bone formation. A biphasic calcium phosphate (BCP)-NC-BMP2-VEGF (BNBV) scaffold was fabricated for this purpose. The sponge BCP scaffold was prepared by replica method and then loaded with 0.5% NC containing BMP2-VEGF. Growth factors were released from NC in a sustainable manner from 1 to 30 days. BNBV scaffolds showed higher cell attachment and proliferation behavior than the other scaffolds loaded with single growth factors. Bare BCP scaffolds and BNBV scaffolds seeded with rat bone marrow mesenchymal stem cells were implanted ectopically and orthotopically in nude mice for 4 weeks. No typical bone formation was exhibited in BNBV scaffolds in ectopic sites. BMP2 and VEGF showed positive effects on new bone formation in BNBV scaffolds, with and without seeded stem cells, in the orthotopic defects. This study demonstrated that the BNBV scaffold could be beneficial for improved bone regeneration. Stem cell incorporation into this scaffold could further enhance the bone healing process.

[Computed tomographic evaluation of the healing of experimental defect of a long bone of the skeleton after implantation into its cavity osteoplastic material "Cerabone®"].

Described in the literature properties of osteoplastic material "Cerabone®" have been obtained from studies in the maxilla and cancellous bone. The lack of data on the impact of «Cerabone®¼ on the dynamics of the healing of defects of compact substance of the long bones of the skeleton dictates the need for such studies. Implantation of osteoplastic material «Cerabone ®¼ was performed into the defect of rat femoral shaft followed by computer-tomographic analysis of its healing. Starting from the 30th day until the end of the experiment (120th day) there were found faint signs of rarefaction in the distal part adjacent to the defect of parent bone, with no signs of bone resorption in its proximal part. There was identified an extremely high density of the implantation site «Cerabone®¼, no visible radiographic evidence of resorption of osteoplastic material and ensuring by the latter the stability of volume of the defect in cortical bone at all stages of the experiment.

Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats.

AIMS: This study aimed to investigate the potential effects of a synthetic apatite (carbonated hydroxyapatite) on the detoxification of a group of male "Wistar" rats exposed to nickel chloride. METHODS: Toxicity was evaluated by rats' bioassay of nickel chloride. Wistar rats received this metal daily by gavage for seven days (4 mg/ml nickel chloride/200 g body weight, BW). To detoxify this organism, a subcutaneous implantation of the apatite is made. RESULTS: The results revealed that exposure to nickel induced oxidative stress, disorders in the balances of ferric phosphocalcic, renal failures, liver toxicity and significant increase in nickel rates in the bones of intoxicated rats. The application of the carbonated hydroxyapatite presented in this study restored those disorders back to normal. The synthetic apatite protected the rats against the toxic effects of nickel by lowering the levels of lipid peroxidation markers and improving the activities of defense enzymes. It also amended ferric and phosphocalcic equilibriums, protected liver and kidney functions and reduced the nickel rate in the bones of the rats. Overall, the results provided strong support for the protective role of carbonated hydroxyapatite in the detoxification of rats exposed to nickel. Those beneficial effects were further confirmed by physico-chemical characterization (X-ray diffraction and infrared spectroscopy), which revealed its property of anionic and cationic substitution, thus supporting its promising candidacy for future biomedical application. CONCLUSION: The hydroxyapatite is an effective biomaterial to solve health problems, particularly detoxification against metals (nickel).

Hydroxyapatite-reinforced in situ forming PLGA systems for intraosseous injection.

In situ forming poly(lactic-co-glycolic acid) (PLGA) implants have not been strongly considered for bone applications because of their poor mechanical properties. Here, in situ forming scaffolds containing hydroxyapatite micro- and nanoparticles were characterized to determine their mechanical properties, injectability, and microarchitecture. Scaffolds were prepared with various concentrations of hydroxyapatite, as well as poly(ß-amino ester) microparticles that facilitate drug delivery. Strength was increased threefold, from 2 to 6 MPa, while compressive modulus was improved sixfold, from 24 to 141 MPa, via the addition of 30% nanohydroxyapatite, which provided greater benefits at equivalent concentrations compared to micro-hydroxyapatite. Scaffolds retained a uniformly porous microarchitecture, and hydroxyapatite particles were distributed evenly throughout the PLGA phase. Injectability, determined by the force required to inject 0.5 mL of material within 60 s, remained clinically acceptable at <50 N at 30% w/w hydroxyapatite and up to 10% w/w PBAE microparticles. Ex vivo injections into intact porcine femoral heads increased compressive modulus of trabecular bone from 81 to 180 MPa and strength from 3.5 to 5.9 MPa. This injectable scaffold offers mechanical reinforcement coupled with previously demonstrated drug delivery potential in a single injection for bone-weakening conditions, such as osteonecrosis or osteoporosis.

Bone neo-formation and mineral degradation of 4Bone.(®) Part I: material characterization and SEM study in critical size defects in rabbits.

OBJECTIVE: This study reports the characterization process and in vivo application of a new high-porosity biphasic calcium phosphate (4Bone(®) - HA 60%/ß-TCP 40%) inserted into the critical size defect of a rabbit tibiae. MATERIAL AND METHODS: Two critical size defects of 6 mm diameter were created in each tibia of 15 New Zealand rabbits, and a total of 60 defects were divided into a test group filled with 4Bone(®) (n = 30) and a control group (n = 30). The material and the implants were characterized by scanning electron microscope (SEM) fitted with energy-dispersive X-ray spectroscopy (EDX). RESULTS: The biomaterial's grain size decreased progressively with the graft integration process over the 60-day study period. Element analysis revealed increased percentages of Ca/P (2.86 ± 0.32 vs. 1.97 ± 0.59) in new bone and at the interface (P < 0.05). Element mapping showed that Ca and P were concentrated in the medullary and cortical zones in the test group but were concentrated only in cortical zones in the control group. CONCLUSIONS: Critical size defects in a rabbit tibia model can be sealed using this highly porous biphasic calcium phosphate; it supports new bone formation, creates a bridge between defect borders, and facilitates bone in growth.