Hydroxyapatite Granules Research Articles

Biodegradable Adhesive (LYDEX) with Hydroxyapatite Granules

A new biodegradable adhesive(LYDEX) which is based on Schiff base formation had developed. LYDEX is easy to control the setting time and degradation speed and it has no risk of infection. In the previous study, LYDEX showed high bonding strength and low cytotoxicity in vitro[1]. In the present study, good bone repair was seen in rat bone defect models, especially in rapidly degrading type. On the other hand, slowly degrading type kept its shape longer without excessive inflammation. In rabbit critical defect model with hydroxyapatite granules (HAs), more newly formed bone was seen in rapidly degrading group and hydroxyapatite group, in 3weeks. In 6weeks, more new bone was seen in slowly degrading type group, whereas, almost no new bone was seen in deep area of the fibrin group, in 12weeks. Direct bonding between HAs and bone was seen in HA group and LYDEX groups. These findings suggest that LYDEX with hydroxyapatite granules can be a promising bone substitute.

Differences of Bone Regeneration by Various Calcium Phosphate/Collagen Composites

Our previous studies showed that synthetic octacalcium phosphate (OCP) enhances bone regeneration more than hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Also, a synthetic bone substitute constructed of synthetic octacalcium phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) showed stable bone regeneration. The present study was designed to investigate the difference of bone regeneration by OCP/Col and other calcium phosphate-collagen composites. OCP/Col, β-TCP$-collagen% composite (β-TCP/Col), or HA$-collagen% composite (HA/Col) sponge was prepared from pepsin-digested atelocollagen isolated from the porcine dermis and OCP, β-TCP, or HA granules, respectively. A standardized critical-sized defect was made in the rat calvarium, and various calcium phosphate-collagen composites were implanted into the defect. The rats were fixed at four weeks after implantation and radiographic and histological examinations were performed by undecalcified cross sections of implants. Radiographic examination showed that uniform radiopaque masses were observed in the created defects treated with OCP/Col, whereas granulous and foggy radiopacity was observed in β-TCP/Col and HA/Col. Histological examination showed that newly formed bone was observed in the reticulum of OCP/Col and around the implanted OCP. The regenerated bone by β-TCP/Col or HA/Col seemed to be less than that by OCP/Col and would not to be nucleated by the granules of β-TCP or HA. The present study indicated that bone regeneration by OCP/Col was different from those of β-TCP/Col and HA/Col. Application of OCP/Col would be expected for clinical use in the future.

Effect of Hydroxyapatite and Zinc-Containing Hydroxyapatite on Osseous Repair of Critical Size Defect in the Rat Calvaria

Hydroxyapatite (HA), widely used as bone graft, can be modified by the incorporation of bivalent cations (Mg2+ and Zn2+) and its gradual release could favor the bone repair. The purpose of this research was to evaluate the effect of the HA and zinc-containing hydroxyapatite (Zn-HA) in the bone repair in rat calvaria in comparison to autogenous bone. Critical size defect in the calvaria was filled with the graft material and the samples were harvested at the 30, 90 and 180 days. The light microcopy observations showed the biocompatibility of the graft materials. In the Zn-HA group the area of neoformed bone was larger than in the HA group, but smaller than in the autograft. A fibrous connective tissue was more evident around HA granules. It could be conclude that the presence of zinc ions in HA crystal accelerated the osteogenesis and increased the area of newly formed bone in relation to HA.

Preparation of Porous Synthetic Nanostructured HA Scaffold

The low temperature macro and micro porous hydroxyapatite scaffold was synthesized. The synthetic nanostructured HA powder was prepared by the reaction of Ca(OH)2 and H3PO4. The ultrasound apparatus was used for the separation of the particles during the precipitation process. Hydrogen peroxide (H2O2) was used as a foaming agent. The samples were dried for 3 hours at 120°C. HA (hydroxyapatite) granules exhibited interconnected macro and micro porosity with the micro pore size in the order of 0.01 'm. The specific surface area of the precipitate reached the average value 64.8 ± 11.9 [m2.g-1]. The compressive strength of the low temperature porous HA scaffold granule was very similar to deproteinized bovine bone and other calcium phosphate ceramic materials used in bone regeneration and prepared by high temperature processes. The porosity of the scaffolds 50-75% was determined by mercury porosimetry. In-vitro cytotoxicity test proved the granules to be non toxic.

Preparation of Spherical Porous Granules Composed of Rod-Shaped Hydroxyapatite and Evaluation of their Protein Adsorption Properties

The present study examined the possibility of using spherical porous granules of hydroxyapatite (HA, Ca10(PO4)6(OH)2) composed of rod-shaped particles as the drug delivery system. The granules composed of rod-shaped HA were successfully prepared by an emulsion method and a hydrothermal treatment. When the rod-shaped granules were soaked in phosphate buffer salines containing lysozyme chloride or albumin, the granules of rod-shaped HA adsorbed more albumin than lysozyme. On the other hand, the HA granules prepared by a normal sintering method adsorbed little lysozyme chloride or albumin. The HA granules composed of rod-shaped particles are expected to be useful as carriers of negatively charged substances.

Histologic Findings at 14 and 18 Years After Cemented Total Hip Arthroplasty With Interface Bioactive Bone Cement Technique

To augment cement-bone bonding in total hip arthroplasty, we interposed hydroxyapatite (HA) granules at the interface. We report the histologic findings of 2 cases 14 and 18 years after cemented total hip arthroplasty with this technique. We found that a thick bony layer was observed where rich layers of HA granules existed. In areas without HA granules, the trabeculae did not form a thick bony layer. These bony layers around HA granules were observed at the interface of non–weight-bearing and weight-bearing areas in 2 acetabula after long-term follow-up.

Effect of Hydroxyapatite porous characteristics on healing outcomes in rabbit posterolateral spinal fusion model

Hydroxyapatite (HA) has been commonly used as a bone graft substitute in various kinds of clinical fields. To improve the healing capability of HA, many studies have been performed to reveal its optimal structural characteristics for better healing outcomes. In spinal reconstruction surgery, non-interconnected porous HAs have already been applied as a bone graft extender in order to avoid autogenous bone harvesting. However, there have been few experimental studies regarding the effects of the structural characteristics of HA in posterolateral lumbar intertransverse process spine fusion (PLF). The aims of this study were to investigate the effect of HA porous characteristics on healing outcomes in a rabbit PLF model in order to elucidate appropriate structural characteristics of HA as a bone graft extender. Thirty-six adult female Japanese White rabbits underwent bilateral intertransverse process fusion at the level of L5-6 without internal fixation. We prepared three types of HA with different porosities: HA with 15% porosity (HA15%), HA with 50% porosity (HA50%), and HA with 85% porosity (HA85%), all of which were clinically available materials. The HA15% and HA50% had few interconnecting pores, whereas the HA85%, which was a recently developed material, had abundant interconnecting pores. All rabbits were randomly divided into the following four groups according to the grafted materials: (1) HA15% + autogenous bone, (2) HA50% + autogenous bone, (3) HA85% + autogenous bone, (4) pure autogenous bone graft. The animals were euthanized at 5 weeks after surgery, and post-mortem analyses including biomechanical testing, radiographical and histological evaluations were performed. There was no statistically significant difference in either fusion rate and/or bending stiffness among the three HA groups. However, in histological and radiological analyses, both bone ingrowth rate and direct bone bonding rate in the HA85% group were significantly higher than those in the HA15% and HA50% groups, despite the similar value of bone volume rate in fusion mass among the three HA groups. In the HA85% group, bone ingrowth was achieved throughout the implanted HAs via interconnecting pores and there was excellent unification between the HA granules and the newly mineralized bone. On the other hand, in the non-interconnected porous HA groups, only a little bone ingrowth could be seen at the peripheral pores of the implanted HA, and its surface was mostly covered with fibrous tissue or empty space. The current study demonstrated that the HA porous characteristics had an effect on the histological outcomes in a rabbit PLF model. We would like to conclude that the interconnected high porous structure seems to be promising for the environment of PLF in the point of producing fusion mass with higher cellular viability. This is because the HA85% is superior in terms of integration with the newly formed bone in fusion mass compared to the non-interconnected porous HAs. However, the porous modifications of HA have little influence on fusion rate and mechanical strength because primary stabilization of the fusion segment is mainly achieved by bridging bone between the adjacent transverse processes outside the implanted materials, rather than the degree of integration between the newly formed bone and the HA granules in PLF.

Use of a novel bone graft substitute in peri-articular bone tumours of the knee

We treated three patients with aneurysmal bone cysts and seven with giant cell tumours who presented with a large osteolytic lesion in peri-articular areas of the knee. The patients age ranged from 8 to 49 years (mean 25 years). The average tumour volume was measured at 39.8 cm 3 (range 18 to 65 cm 3). The tumour cavities were treated with curettage, phenolisation and application of a composite bone graft substitute containing 35% calcium-sulphate hemihydrate and 65% hydroxyapatite granules. All patients were followed up for 4.0 to 5.2 years (mean 4.5 years). Tumour recurrence was noted in two cases. In the remaining patients consolidation of the lesion was considered complete at a mean of 4.5 months (3–6.5 months). During follow-up no deformities developed and no radiological signs of joint degeneration were noted. All patients regained close to normal function, with a mean Musculoskeletal Tumour Society Rating Score of 95.1%. Due to their good osteoconductive abilities, composite synthetic bone graft substitute combining porous hydroxyapatite with calcium-sulphate appears to be an effective alternative to autologous cancellous bone graft in the treatment of large osteolytic lesions in peri-articular areas around the knee joint. They bear major advantages through ubiquitous availability and the avoidance of morbidity associated with iliac crest harvest. Concerns remain as the radio-opaque appearance of the bone graft substitute may potentially delay the detection of tumour recurrence.

Acetabular Reconstruction Using a Cementless Cup and Hydroxyapatite Granules: 3- to 8-Year Clinical Results

We investigated 17 patients undergoing consecutive revision or conversion total hip arthroplasties with a cementless cup for acetabular bone defects. Patients were all women and the average age at the time of surgery was 61.2 years. All bone defects were filled and packed with porous hydroxyapatite (HA) granules. The average follow-up was 5.6 years (range, 3-8 years). The average Merle d'Aubigné functional hip score was 15.6 at the latest follow-up vs 11.6 before surgery. No patients needed additional revision surgery. In 4 cases in which a superior deficiency had been covered with HA granules, the cup migrated superior to the host bone but without any detrimental effect. The remaining 13 cases showed no migration of the cup. We conclude that acetabular reconstruction with a cementless cup and HA granules seems to provide encouraging intermediate results.

Heat‐shock‐induced three‐dimensional‐like proliferation of mouse fibroblasts mediated by hydroxyapatite

The aim of the present study was to determine both the minimal and the optimal conditions under which heat treatment is effective for enhancing 3D (three-dimensional)-like cell proliferation. C3H10T1/2 mouse fibroblasts were cultured with hydroxyapatite granules for 10 weeks after heat treatment at 40, 41.5, 43, 44 or 45 degrees C for 2, 10, 15, 20, 30, 45, 60, 90, 180 and 360 min. Then minimal and optimal conditions of temperature and duration of heat treatment for induction of 3D-like proliferation of cells were determined. The minimal conditions of heat treatment to induce 3D-like proliferation were 43 degrees C for 2 min and the optimal conditions were 43 degrees C for 10 min. The mean rates of formation of 3D-like proliferation patterns by cells heat-treated at 43 degrees C for 2 and 10 min were significantly higher (1.7- and 3.7-fold respectively) than that by untreated cells (P<0.05). We also observed significantly greater effects of heat treatment on 3D-like proliferation at 40 degrees C for 90 or 180 min and at 41.5 degrees C for 15 min and 44 degrees C for 10 min. We found that apoptosis had occurred in 7.5 and 87.0% of the cells at 1 week after heat treatment at 43 degrees C for 10 min and 30 min respectively. Western-blot analysis demonstrated that phosphorylation of p38 MAPK (mitogen-activated protein kinase) was markedly increased by heat treatment at 43 degrees C for 10 min. These findings suggest that activation of p38 MAPK by heat shock is associated with 3D-like cell proliferation. The results of the present study should be useful for further studies aimed at elucidation of the physiological mechanisms underlying thermotherapy and hyperthermia.

Exogenous Recombinant Human BMP-2 Has Little Initial Effects on Human Osteoblastic Cells Cultured on Collagen Type I Coated/Noncoated Hydroxyapatite Ceramic Granules

Tissue engineering of bone entails the successful interplay between osteoinductive factors, osteogenic cells, their extracellular environment, and an osteoconductive biomaterial scaffold. Naturally produced ceramics, like hydroxyapatite (HA) calcified from red algae, are the most promising materials for use as scaffolds in this field. We hypothesized that extracellular matrix compartments and osteoinductive factors could further ameliorate the bioactivity of the scaffold. Osteosarcoma cells with proven osteogenic phenotype (SaOS-2) were cultured onto type I collagen coated (Coll I/HA) and noncollagen coated HA granules (NC/HA) gained from red algae (C GRAFT/Algipore). Cells grown on tissue culture polystyrene dishes (TCPS) were used as controls. Second, SaOS-2 cells cultured on Coll I/HA, NC/HA, and TCPS were treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in different concentrations (10, 100, and 500 ng/mL). Non rhBMP-2-treated cultures were used as controls. Cultures of both experiments were grown under osteogenic differentiation conditions and after 24, 48, and 72 hours assays for cell viability, apoptosis, alkaline phosphatase activity (ALP), and osteocalcin (OC) secretion were done. Coating of HA granules with type I collagen showed higher cell viability in rhBMP-2-treated and nontreated cells. Supplementation of cultured cells with exogenous rhBMP-2 showed a dose-dependent effect only in the TCPS group. No alterations of the apoptotic rate within 1 investigation group were found. Addition of rhBMP-2 did not significantly alter the specific OC secretion of cells grown on Coll I/HA and TCPS. These in vitro findings show that in the initial period of cultivation and up to 72 hours, the coating of HA granules with collagen type I had positive effects on cell viability and osteoblastic characteristics of osteoblastic cells. In contrast, the supplementation with exogenous rhBMP-2 shows no dose-dependent effects. The combination of collagen type I and exogenous rhBMP-2 did not ameliorate the bioactivity of hydroxyapatite calcified from red algae in the initial period of cultivation.

Clinical Results of Total Knee Arthroplasty by Using Improved Cement Technique by Interposing Hydroxyapatite Granules

Improved cement technique by interposing less than two layers of hydroxyapatite (HA) granules between bone and bone cement at the cementing (Interface Bioactive Bone Cement : IBBC) have been performed in total knee arthroplasty (TKA). 140 knees (120 patients) could be followed up clinically and radiologically. As a control, clinical results of TKA with conventional cementing (Non-IBBC) were used. In IBBC cases, the appearance rate of the radiolucent lines on the tibial components and the periprosthetic osteolysis of the tibial components were significantly low. In IBBC, bone cement bound to HA mechanically immediately after surgery and HA granules bound to the bone physicochemically after bone ingrowth into the spaces around the HA granules. Thus, we believe that IBBC is a method combining the advantage of cementless HA coating and bone cement.

Selective Bone Formation on Hydroxyapatite-Granule-Implanted Titanium

Hydroxyapatite (HA)-granule-implanted cylindrical titanium composites, which uniformly have HA granules on the curved surface, were formed by a hot pressing using HA-granuleimplantation system under the conditions of 1023 K, 1 h, 1960 N in vacuo. Cracks were not observed in the HA granules. The HA-granule-implanted titanium samples were implanted in a mandible of a dog. After 1 year, new thin bones like pillars were selectively structured on the HA granules with bone induction ability. The HA-granule-implantation technique is expected to be useful for designing shape of bone around titanium implant in order to match living bones.

Preparation of a Bioactive Xenograft

The method which gives a low crystalline hydroxyl carbonated apatite forming ability to originally non-bioactive high crystalline hydroxyapatite surface was newly developed. The granules of trabecular bovine bone, which had a size range from 212 to 1000 μm, were defatted, deproteinized, and then heat-treated at 1000 oC for 3 hours to remove organics completely. They were treated with the mixed solution of calcium chloride and calcium hydroxide in Soxhlet’s apparatus at 100 oC for 3 days and then dried completely. Low crystalline hydroxyl carbonated apatite was observed to occur on the surface of high crystalline hydroxyapatite granules after soaking them into the simulated body fluid (SBF) for 1 week. This method is likely to have a potential to be used as a new process to give a bioactivity to originally non-bioactive materials.

Nanohydroxyapatite microspheres as delivery system for antibiotics: Release kinetics, antimicrobial activity, and interaction with osteoblasts

Severe periodontitis treatment, where massive alveolar bone loss occurs, involves bone defect filling and intensive systemic log-term antibiotics administration. This study aims at developing novel injectable drug delivery systems (nanohydroxyapatite microspheres) with the drug releasing capability for periodontitis treatment and simultaneously initiating the osteointegration process. Materials were characterized by XRD, SEM, inverted stand optical microscope analysis, and mercury porosimetry method. Amoxicillin, amoxicillin + clavulanic acid, and erythromycin were the antibiotics used. Release properties during 28 days from the hydroxyapatite (HA) granules, and two types of nanoHA microspheres were investigated. Biocompatibility was assessed by cytotoxicity assays. HA granules were inadequate, releasing all antibiotic during the first hours. The concentration of antibiotics released in the first days from HA-2 was higher than from HA-1 microspheres, because of the increased porosity and surface area. The release profiles (fast initial release followed by long-term sustained release) of effective doses of antibiotics make these systems good alternatives for antibiotics delivery. Osteoblasts proliferated well on both types of microspheres, being cell growth enhanced in the presence of antibiotics. Erythromycin presented the most beneficial effect. Combining the sustained antibiotic release with the osteoconduction, resorbability, and potential use as injectable bone filling material of porous HA microspheres, these systems provided a forth fold beneficial effect.

Encapsulation of Protein-Loaded Hydroxyapatite Granules with Poly (lactic-co-glycolic acid)

A solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation method was applied to encapsulate protein-loaded hydroxyapatite (HAp) granules (D50=19.5 μm) with a biodegradable polymer of poly (lactic-co-glycolic acid) (PLGA). After loading bovine selum albumin (BSA), the HAp granules were mechanically dispersed in oil phase (PLGA dissolved in CH2Cl2), and then the suspension was dropped into water containing an emulsion stabilizer of polyvinyl alcohol (PVA). Stirring of the dropped suspension in the water phase produced S/O/W emulsions. The emulsions were diluted with excess water to facilitate removal of the organic solvent (CH2Cl2) from the oil phase. After the evaporation of CH2Cl2, the particulate materials were separated, washed and vacuum-dried. The resultant particles had very smooth PLGA surface with spherical shape, and their mean particle size was about several microns larger than that of the HAp granules. Fluorescently-labeled confocal laser scanning microscopy (CLSM) revealed that the protein-loaded HAp granules were encapsulated in the PLGA microsphere.

Update on the Use of Hydroxyapatite Granules in Aesthetic and Reconstructive Facial Surgery

Augmentation of the craniomaxillofacial region is required for many aesthetic and reconstructive procedures. Although a variety of different materials and techniques have been described, hydroxyapatite granules seem to be the ideal material. They can provide the exact shape and size of the area to be augmented. In this study, the surgical technique with the results and the complications, derived from a retrospective review of patient charts between January 1981 and November 2006, are reviewed. Included in the study were 524 procedures in 270 patients, treated between January 1981 and November 2006. The mean postoperative follow-up was 11 months (range, 1 to 121 mos). Almost half (46.7%) of patients had one area augmented while the remainder had either two or more areas treated. The range of weight of hydroxyapatite granules injected was 0.4 to 8.0 gm (mean, 2.2 gm). The distribution of the injection sites were maxilla (48.1%), mandibula (21.9%), zygoma (12.2%), mentum (4.4%), nose (1.9%), temporal bone (3.1%), periorbital (6.1%), frontal (1.9%), and hard palate (0.002%). In the 524 procedures, there were 39 complications (7.4% of all cases). Contour irregularity was the most common complication, followed by seroma, hematoma, extrusion and gravity displacement, and infection. After a 25-year experience, we know that hydroxyapatite granules can be placed into a preformed cavity and can be molded by hand to obtain the desired reconstruction. Complications are few. The technique is simple and quick. Any bony facial area can be altered and cost is much lower than other implants.

Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.

Transpedicular hydroxyapatite grafting with indirect reduction for thoracolumbar burst fractures with neurological deficit: A prospective study.

Background:The major problem after posterior correction and instrumentation in the treatment of thoracolumbar burst fractures is failure to support the anterior spinal column leading to loss of correction of kyphosis and hardware breakage. We conducted a prospective consecutive series to evaluate the outcome of the management of acute thoracolumbar burst fractures by transpedicular hydroxyapatite (HA) grafting following indirect reduction and pedicle screw fixation.Materials and Methods:Eighteen consecutive patients who had thoracolumbar burst fractures and associated incomplete neurological deficit were operatively treated within four days of admission. Following indirect reduction and pedicle screw fixation, transpedicular intracorporeal HA grafting to the fractured vertebrae was performed. Mean operative time was 125 min and mean blood loss was 150 ml. Their implants were removed within one year and were prospectively followed for at least two years.Results:The neurological function of all 18 patients improved by at least one ASIA grade, with nine (50%) patients demonstrating complete neurological recovery. Sagittal alignment was improved from a mean preoperative kyphosis of 17°to −2°(lordosis) by operation, but was found to have slightly deteriorated to 1° at final followup observation. The CT images demonstrated a mean spinal canal narrowing preoperatively, immediate postoperative and at final followup of 60%, 22% and 11%, respectively. There were no instances of hardware failure. No patient reported severe pain or needed daily dosages of analgesics at the final followup. The two-year postoperative MRI demonstrated an increase of one grade in disc degeneration (n = 17) at the disc above and in 11 patients below the fractured vertebra. At the final followup, flexion-extension radiographs revealed that a median range of motion was 4, 6 and 34 degrees at the cranial segment of the fractured vertebra, caudal segment and L1-S1, respectively. Bone formation by osteoconduction in HA granules was unclear, but final radiographs showed healed fractures.Conclusions:Posterior indirect reduction, transpedicular HA grafting and pedicle screw fixation could prevent the development of kyphosis and should lead to reliable neurological improvement in patients with incomplete neurological deficit. This technique does not require fusion to a segment, thereby preserves thoracolumbar motion.

Improved Malar Projection with Transconjunctival Hydroxyapatite Granules

Improved Malar Projection with Transconjunctival Hydroxyapatite Granules