Hydroxyapatite Granules Research Articles

Postoperative lumbar spinal stenosis after intertransverse fusion with granules of hydroxyapatite: a case report

In the present case of postoperative lumbar spinal stenosis after non-instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone union was not completed and the patient felt the recurrence of his symptoms within two years. We performed re-decompression with fusion, and in hematoxylin and eosin staining of HA granulation harvested during revision surgery, fibrous tissue with hyaline degeneration surrounded the cavity where the HA had existed. Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal layer of the cavity, and no obvious bony bridge had regenerated from autologous bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be seen in the new bone, suggesting that the activity of osteoclasts in the new bone decreased during the seven years after the primary surgery.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3483360258050263

Development and clinical cases of injectable bone void filler used in orthopaedic

This study reports several clinical cases for orthopaedic bone regeneration using an injectable bone substitute (MBCP Gel®) to demonstrate its safe use and efficiency in clinical applications. The biomaterial is a composite of microporous bioceramic hydroxyapatite granules that are associated with beta tricalcium phosphate (MBCP) and a synthetic hydrosoluble polysaccharide hydrogel (CE mark 123 and FDA dental domain registered). The present exploratory study demonstrated the generative osseous performance of this injectable bioceramic for filling various orthopaedic bone defects. The clinical cases showed bone ingrowth into the cavities created by drilling when removing the aseptic osteonecrosis of the femoral head during biopsy taking. Furthermore, bone reconstruction was seen after filling large cystic defects, at the time of the revision surgery of the hip prosthesis. Resorption and bone ingrowth with trabecular bone architecture were observed in defects created in long bones (femur and tibia). Patients were followed during 5 months to 1 year. The overall results demonstrated the safe use and the clinical performance of this injectable bioceramic in orthopaedics.

Heterobifunctional Poly(ethylene glycol) Derivatives for the Surface Modification of Gold Nanoparticles Toward Bone Mineral Targeting

Heterobifunctional poly(ethylene glycol)s can be used for many biomedical applications ranging from solubility enhancement of hardly soluble compounds to surface modification of medical devices. In order to modify gold nanoparticles as model particles for drug targeting applications, PEG derivatives are synthesized that possess a high affinity for gold surfaces, namely a thioalkyl function, known to form stable monolayers on gold. Additionally a bisphosphonate function is introduced in the PEG molecule to allow targeting of hydroxyapatite rich tissues, like bone. Gold nanoparticles are modified using the synthesized bifunctional PEG and investigated for their stability in biological fluids and their ability to bind to hydroxyapatite granules in these fluids.

Efficacy of Platelet Rich Plasma and Hydroxyapatite Crystals in Bone Regeneration After Surgical Removal of Mandibular Third Molars

This study evaluates the efficacy of platelet rich plasma (PRP) & porous hydroxyapatite crystals in bone regeneration after surgical removal of mandibular third molar with the help of radiographs and its comparison with control side. A total of 40 patients; both male and female aged between 18 and 35years, who had impacted mandibular third molars were randomly selected for this study. Twenty patients were taken for control group and 20 patients for study group. The extraction socket of the study group was packed with PRP and hydroxyapatite granules and that of control group was sutured without PRP and hydroxyapatite. The bone density of both extraction sockets were evaluated radiographically using gray level histogram and compared periodically on immediate postoperative day, 1st and 3rd month postoperatively and postoperative sequelae of both the control group and study group in terms of oedema & pain or any other adverse reactions were also assessed. Data suggested evidence of early bone formation and maturation radiographically in study group as compared to control group. The percentage of facial swelling was numerically greater on the control side as compared to the study side, Pain was also assessed with VAS and it was found that the severity of pain was equal in both study and control groups and the results were not significant. This study clearly indicated a definitive improvement in the wound healing, increase in bone density, which signifies and highlights the use of PRP and hydroxyapatite granules, certainly as a valid method in inducing and accelerating bone regeneration.

Synthesis of nanosized porous hydroxyapatite granules in hydrogel by electrophoresis

Nanosized porous hydroxyapatite (HA) granules are expected to be useful as DNA and drug carriers for cells. We attempted to synthesize nanosized HA granules in an agarose gel by electrophoresis of calcium and phosphate ions. Wells were prepared on an agarose gel, and a CaCl2 solution was placed in the wells on the positive side and a Na2HPO4 solution was placed in the wells on the negative side. After a potential was applied, white precipitates appeared in the gel. The precipitates were calcium-deficient HA granules of approximately 300–600nm in diameter. These granules were composed of fiber-like particles and had a porous structure. The diameters of the granules were decreased by an increase in the gel concentration. Hence, we successfully synthesized nanosized porous HA granules to be used as DNA and drug carriers.

Bovine hydroxyapatite (Bio-Oss®) induces osteocalcin, RANK-L and osteoprotegerin expression in sinus lift of rabbits

PurposeThe aim of this study was to analyze and compare the expression of osteocalcin, RANK-L, osteoprotegerin, in sinus lift procedures using bovine hydroxyapatite (HA). Material and methodsTwenty four male rabbits underwent bilateral sinus lift procedures were distributed into two groups, according to the sinus filling material: Group 1) autogenous bone graft; and Group 2) bovine HA. All groups were sacrificed after 14 and 30 days, for microscopic and immunohistochemistry analysis. ResultsAt 14 days after surgery, discrete osteogenesis was observed in the highly vascularized granulation tissue surrounding HA particles, as well as woven bone deposition on the biomaterial surface. Following 30 days, well organized bone trabeculas were seen surrounding the HA granules presenting areas of osteogenic activity. Morphometric findings did not show remarkable differences between groups. Bovine HA induced similar osteocalcin, RANK-L, osteoprotegerin immunoexpressivity when compared to autogenous bone graft group for both periods evaluated in this setting. ConclusionTaken together, these data are consistent with the notion that HA has a similar biological behavior to autogenous bone graft in sinus lift of rabbits.

Functionalisation of porous hydroxyapatite for bone substitutes

Abstract Calcium phosphate ceramics such as hydroxyapatite (HA) have been widely used to repair and reconstruct damaged parts of the human skeleton. This material is currently available as injectable cements, granules or macroporous blocks. The most common materials are granules because of their ability to be implanted in the human body. In this study, a new manufacturing procedure to fabricate either dense or microporous or macroporous hydroxyapatite spherical granules based on a lost wax method and leading to beads with a fully controlled porosity was developed. The as-obtained HA granules porous structure was impregnated by gentamicin and lambda phage and the antibiotic and phage releasing kinetics were studied as a function of time and porosity.

Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine

Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro- and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a “splitting” test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)—the cracks, in comparison, weaken the structure by one to two orders of magnitudes.

A Long Term Histological Analysis of Effect of Interposed Hydroxyapatite between Bone and Bone Cement in THA and TKA

The standard cementing technique for total hip and knee arthroplasty (THA, TKA) was modified by interposing osteoconductive porous polycrystalline hydroxyapatite (HA) granules at the cement-bone interface to augment cement-bone bonding. Twenty-one specimens from the acetabulum and two specimens from the femur containing well-fixed bone-cement interface were retrieved five months to twenty-two years after THA and TKA with an interface bioactive bone cement technique. Histological findings were evaluated in terms of the retrieved sites, the interval between index operation and revision, patient age at retrieval and bone pathology. Dense bone ingrowth was observed in all specimens retrieved from the superior wall of the acetabulum. Cancellous bone ingrowth was observed in specimens retrieved from the infero-medial wall of the acetabulum. Connective tissue interposition and osteolysis were observed at the sites where hydroxyapatite granules were absent. Findings of bone ingrowth for the HA interposed retrievals were similar regardless of the interval between index operation and revision, patient age at retrieval, and bone pathology. Longer survivability of the bone-cement bonding was attributed more to the interposed HA granules. In spite of various degrees of aging, postmenopausal osteoporosis, and pathological bone condition the histological findings were not affected by the bone pathology. There was long-term direct contact between the bone and hydroxyapatite granules. Thus, the interface bioactive bone cement technique can ensure longevity of bone-cement bonding even after the onset of osteoporosis and for pathological bone conditions.

The comparative effectiveness of granules or blocks of superporous hydroxyapatite for the treatment of intrabony periodontal defects

The aim of the present controlled clinical study was to compare the clinical response of grafting superporous hydroxyapatite (HAp) granules to superporous HAp blocks in the treatment of human intrabony periodontal defects. Twenty interproximal intrabony os-seous defects in 20 healthy, non-smoking subjects diagnosed with chronic periodontitis were included in this study. These twenty subjects were randomly assigned to either the HAp granule or the HAp block groups. Clinical and radiographic measurements were determined at baseline, 3, 6, 9 and 12-month post-surgical evaluation time periods. When compared to baseline, the 12-month results indicated both treatment procedures resulted in statistically significant favorable changes in probing depth (mean value: 3.5 mm versus 3.5 mm), clinical attachment level gain (3.2 mm versus 2.3 mm) and radiographic infrabony defect depth decrease (2.9 mm versus 2.5 mm) for HAp granule and HAp block grafting respectively. At 3- and 6-months, the granule group, when compared to the block group, exhibited a statistically significantly more favorable clinical response in clinical attachment level (4.1 mm versus 5.9 mm, p < 0.05 at 3-months; 4.3 mm versus 6.5 mm, p < 0.01 at 6- months). The present study demonstrated that both grafting of superporous HAp granules and grafting of HAp blocks were similarly successful in the treatment of human intrabony periodontal defects.

Stimulation of Osteogenesis in Bone Defects Implanted with Biodegradable Hydroxyapatite Composed of Rod-Shaped Particles under Mechanical Unloading

The aim of this study was to evaluate the influence of mechanical unloading on the repair of bone defects with implantation of biodegradable bone substitutes. Spherical granules of biodegradable hydroxyapatite composed of rod-shaped particles (RHA) or beta-tricalcium phosphate composed of rod-shaped particles (RTCP) were implanted into a bone defect created in the distal end of the right femur of 8-week-old Wistar rats. Two, 6, 10, and 22 weeks after implantation, part of the sciatic nerve in the thigh was resected and exposed to mechanical unloading for 2 weeks. Then, 4, 8, 12 and 24 weeks after implantation, repair of the bone defect was analyzed. As a control, the bone defect without implantation of ceramic granules was also analyzed. Both RHA and RTCP tended to be reduced, but the reduction was not obvious during the experimental period. At 12 and 24 weeks after implantation, the amount of newly formed bone in the animal implanted with RHA was significantly greater than that at 4 weeks after implantation, but that in the animal implanted with RTCP or without implantation was not significantly different. The number of osteoclasts in the region implanted with RHA was significantly larger than that of the region implanted with RTCP or without implantation at 12 and 24 weeks. The activities of alkaline phosphatase in osteoblasts and tartrate-resistant acid phosphatase in osteoclasts were remarkably increased in the bone defects with implantation compared with those in the bone defects without implantation. These results suggested that RHA stimulated osteogenesis and osteoclastogenesis even after 2 weeks of mechanical unloading, and that RHA could be expected to improve the repair of bone defects in patients under the condition of skeletal unloading.

Crestal minimally-invasive sinus lift on severely resorbed maxillary crest: prospective study

This case series aimed to explore the clinical outcome of sinus floor elevation surgery using a crestal approach technique in case of severely resorbed maxillae. Seventeen edentulous patients received 20 implants and sinus floor elevation in posterior maxillae with residual crestal height of 1.2-5.0 mm and >7 mm. Drilling perforation was performed until the sinus floor was felt; the sinus mucosa was then lifted and magnesium-enriched hydroxyapatite granules (Mg-e HAP) were placed; and implants were immediately inserted. Four months later, definitive crowns were cemented, and patients were followed up for 24 months. Implant failures and complications 24 months after prosthetic loading were noted, and radiographic regenerated bone height was measured. No patient dropped out, and all implants were successfully osseointegrated. There was minimal postoperative patient discomfort, and the only complication was a minimal perforation of the sinus membrane with no negative consequences. At the time of implant insertion, the residual crestal height mean value was 4.12 mm. After surgery and at the last follow-up, the mean heights of bone were 13.51 and 12.98 mm, respectively. The procedure was able to obtain sinus elevation and implant osseointegration.

Fluoride-Treated Bio-Resorbable Synthetic Hydroxyapatite Promotes Proliferation and Differentiation of Human Osteoblastic MG-63 Cells

When resorbable hydroxyapatite (HA) granules, which are used as a bone supplement material, were treated in neutral 4% sodium fluoride (NaF) solution, formation of a reactant resembling calcium fluoride was observed on the surface of the granules. Immediate and slow release of fluoride from fluoridated HA (HA+F) granules was observed after immersion in culture fluid, and the concentration increased over time to 1.25 ± 0.05 ppm F at 0.5 hours, 1.57 ± 0.12 ppm F at 24 hours, and 1.73 ± 0.15 ppm F at 48 hours. On invasion assay, migration of human osteoblast-like MG-63 cells exposed to the released fluoride was confirmed in comparison to the cells incubated with a nonfluoridated control sample (P < .01). In addition, fluoride added to the medium increased MG-63 cell proliferation in a manner dependent on fluoride concentrations up to 2.0 ppm (P < .05). At 5.0 ppm, however, fluoride significantly inhibited cell proliferation (P < .005). Activity of the osteogenic differentiation marker, alkaline phosphatase (ALP), also increased with fluoride after exposure for 1 week, increasing significantly at 1.0 ppm (P < .05). The promotion of MG-63 cell migration and proliferation, as well as increased ALP activity, suggested that fluoride released from the surface of resorbable HA granules, which were fluoridated by prior treatment with neutral 4% NaF solution, can provide a superb method to supply fluoride and promote osteogenic cell differentiation.

Osteoconductive Capacity of Hydroxyapatite Implanted Into the Skull of Diabetics

Diabetes mellitus can cause various diseases, including loss of bone mineral density as a characteristic manifestation of osteoporosis. In this condition, bone is more vulnerable to pathologic fractures that can be treated by implantation of biomaterial grafts. The aim of this study was to evaluate the osteogenic capacity of hydroxyapatite implanted into bone defects in the skull of nonobese diabetic mice. Fifteen nonobese diabetic mice were divided into 3 groups: control (nondiabetic), spontaneously diabetic, and spontaneously diabetic receiving insulin replacement applied subcutaneously into the dorsum. Defects were created experimentally in the skull with a surgical bur and filled with hydroxyapatite granules. The animals were killed 4 weeks after surgery, and samples were obtained for analysis. Quantitative methods were used for measurement of the new bone formation. Data were analyzed by analysis of variance followed by the Tukey test (P < 0.05). Radiographic results showed good radiopacity of the hydroxyapatite; however, radiolucent spots were seen between the hydroxyapatite granules in the diabetic groups, indicating infiltration of connective tissue. Microscopic results showed projections of newly formed bone from the margin of bone defect toward the implant. The quantity of newly formed bone was significantly higher (P < 0.05) than that observed in the diabetic groups. The recipient area of diabetic groups contained a larger amount of connective tissue as demonstrated by radiographic analyses. In conclusion, the osteogenesis guided by the properties of hydroxyapatite may even occur in bone suffering from the effects of diabetes, but the quantity of newly formed bone is lower, and the process is slower.

Evaluation of the bone repair in defects grafted with hydroxyapatite and collagen membrane combined with laser therapy in rats

Bone regeneration is the result of cellular events such as osteogenesis and neovascularization. However, implantation of autogenous grafts may be necessary in cases of bone mass loss due to high impact trauma. The disadvantages of the latter approach include morbidity of the donor area. Biomaterials represent an alternative for bone restoration. The most widely used compounds are collagen or hydroxyapatite membranes because of their biocompatibility and osteoconductivity. Laser therapy has been applied in combination with these implants to accelerate bone regeneration. The objective of this study was to evaluate the effects of low-level laser therapy (LLLT) on the healing of rat left tibial bone defects filled with hydroxyapatite or collagen membrane. Twenty rats were used. Surgical bone defects were created in the proximal third of the left tibia, and the animals were divided into four groups according to treatment: animals receiving hydroxyapatite implants (group H), animals receiving collagen implants (group C), animals treated with hydroxyapatite plus LLLT (group HL), and animals treated with collagen membrane plus LLLT (group CL). The animals were sacrificed 8 weeks after surgery, and the bone samples were obtained for analysis. Histomorphometrical methods were used for new bone quantification. Data were analyzed by analysis of variance (p &amp;lt; 0.05). Histological analysis showed the formation of new bone in the implant area with cortical aspect in groups. Bone neoformation was also demonstrated on radiographs as radiopacity of the hydroxyapatite granules and of the contour of the defects implanted with the collagen membrane. However, no significant difference for new bone formation was observed between the groups studied. The biomaterials used were presented good osteoconduction; however, the laser therapy protocol used was not adequate to accelerate the osteogenic process in the bone defect regeneration in the advanced bone healing process.

Incorporation of strontium up to 5 Mol. (%) to hydroxyapatite did not affect its cytocompatibility

The aim of this work was to produce hydroxyapatite (HA) granules containing 0, 0.5, 1 and 5 mol. (%) of strontium (Sr), evaluate the physico-chemical properties and also the cytotoxicity by three different parameters of cell viability (ISO 10993-5, 10993-12). The physico-chemical characterization was carried out by using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and X-ray fluorescence (XRF). The XRD profile presented the main peaks of HA (JCPDS 860740) and the absorption bands of HA were identified by FTIR. The XRF results showed that the strontium concentration was close to the theoretical value. Regarding the cytotoxicity assays, the incorporation of strontium up to 5 mol. (%) to the HA did not affected dehydrogenase activity (XTT, 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide), membrane integrity (neutral red uptake) or DNA contend (incorporation of crystal violet), in relation to HA alone. In conclusion, hydroxyapatite containing from 0.5 to 5 mol. (%) of Sr was successfully produced and presented no cytotoxicity.

Osseoinduction Evaluation of Hydroxyapatite and Zinc Containing Hydroxyapatite Granules in Rabbits

This study investigated the osteoinductive potential of granules of stoichiometric hydroxyapatite (HA) and 0.5% zinc containing hydroxyapatite (ZnHA) in intramuscular (IM) site of rabbit’s abdomen. The biomaterials were both used in granular form, with 75% porosity and particle diameter between 450 and 500μm, sintered at 1100°C. Both materials performed adequately on a multiparametric in vitro cytocompatibility assay, indicating their suitability for in vivo testing. After approval by the Ethics Commission on Teaching and Research in Animals, fifteen rabbits were submitted to general anesthesia, incision and tissue dilatation, and a small site was created for HA (right incision) and ZnHA (left incision) intramuscular implantation. The animals were killed after 2, 4 and 12 weeks for biomaterials and surrounding tissues removal. Histological analysis after 2 weeks revealed the presence of granulation tissue surrounding biomaterials with multinucleated giant cells and no newly formed bone for both materials. After 4 weeks there was fibrous tissue involving the material and few inflammatory cells. Following 12 weeks it was observed the presence of connective tissue surrounding the biomaterial, cellularized enough for the two experimental groups, but it was not observed the presence of bone matrix associated with the biomaterials. We conclude that both biomaterials are cytocompatible and did not present the property of osseoinduction after 12 weeks of implantation.

Cytocompatibility and Structural Arrangement of the Collagen Fibers: An &lt;i&gt;In Vitro&lt;/i&gt; and &lt;i&gt;In Vivo&lt;/i&gt; Evaluation of 5% Zinc Containing Hydroxyapatite Granules

Hydroxyapatite (HA) is one of the most employed materials for bone therapy due to its structural similarity with bone, its biocompatibility and physicochemical properties. Additionally, HA performance may be improved by ionic substitution of calcium with divalent bioactive metallic cations such as zinc. In this context, zinc incorporation into HA have been well studied, in spite of conflicting results regarding its biocompatibility: while previous reports on in vitro cytocompatibility have described 5% zinc containing HA (ZnHA) as slightly cytotoxic, this material presented an excellent response on in vivo studies. In order to bring more information on ZnHA biocompatibility, we performed a multiparametric assay evaluating sequentially on the same cells three different viability parameters: mitochondrial activity (XTT), membrane integrity (Neutral Red) and cell density (Crystal Violet Dye Exclusion test). Additionally, we intended to complement the existing data on ZnHA in vivo performance, by assessing its ability to affect the arrangement of collagen fibers on the grafted area, an important indicative of bone maturation. MC3T3-E1 cells were exposed to 24-hours extracts of ZnHA or stoichiometric HA on culture medium (DMEM) and cell viability was assayed. ZnHA was very cytocompatible, since the levels of viable cells on all 3 tests were similar to the HA and polystyrene (negative control) extracts, but significantly higher than cells treated with 4% phenol (positive control). For the in vivo studies, critical size defects in rats calvaria were filled with HA or ZnHA granules. The histological evaluation after 30 and 180 days revealed an increase along time. Event tough ZnHA is cytocompatible the presence of Zn was unable to alter the interaction between collagen fibers and the mineral bone phase, as compared to stoichiometric HA.

Characterisation and photocatalytic activity of structure-controlled spherical granules of an anatase/hydroxyapatite composite

Materials that can purify the environments are desirable. Anatase (TiO 2) has received attention because it is stable and can decompose organic substances because of its photocatalytic activity. To make use of anatase effectively, we deposited nano-sized anatase particles on porous hydroxyapatite (HA) ceramics composed of rod-shaped particles. Spherical porous HA granules composed of rod-shaped HA particles were prepared using a hydrothermal process. The granules were soaked in a solution containing a water-soluble titanium complex and then hydrothermally treated. Nano-sized anatase particles were deposited on each rod-shaped HA particle. The anatase/HA granules composed of rod-shaped HA particles showed higher photocatalytic activity than those composed of globular HA particles. The granules are expected to be useful as an environment-purifying material with high manageability and photocatalytic activity.

Bone Regeneration Using Porous Titanium Particles versus Bovine Hydroxyapatite: A Sinus Lift Study in Rabbits

The first objective of this study was to qualitatively and quantitatively assess the bone formation process, particularly the long-term behavior and three-dimensional volume stability of subsinusal bone regeneration, using titanium (Ti) or bovine hydroxyapatite (BHA) granules, in a rabbit model. The second objective was to evaluate the effect of the hydration of the BHA particles with a therapeutic concentration of doxycycline solution on the osteogenesis and biomaterial resorption. Rabbits underwent a double sinus lift procedure using one of three materials: grade 1 porous Ti particles, BHA, or BHA hydrated with doxycycline solution (0.1mg/ml) (BHATTC). Animals were sacrificed after 1 week, 5 weeks, or 6 months. Samples were analyzed using µCT and nondecalcified histology. The materials used in each of the three groups allowed an optimal bone formation; bone quantities and densities were not statistically different between the three groups. At 6 months, more stable three-dimensional volume stability was found with Ti and BHATTC (p=.0033). At 5 weeks and 6 months, bone to material contact corroborating osteoconduction was significantly higher with BHA and BHATTC than with Ti (p<.0001). Even though the studied biomaterials displayed different architectures, they are relevant candidates for sinus lift bone augmentation prior to dental implants because they allow adequate three-dimensional stability and osteogenesis. However, to recommend the clinical use of Ti, both an observation on the drilling effects of Ti particles and clinical trials are needed.