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Hydroxyapatite does not improve the outcome of a bipolar hemiarthroplasty.

In a one-surgeon study the clinical and radiographic results of 30 cementless bipolar hip prostheses in 24 patients younger than 55 years were evaluated. Eleven noncoated prostheses (Noncoated Group) and 19 hydroxyapatite-coated prostheses (Hydroxyapatite Group) were compared after a mean followup of 10.4 years. The Harris hip score increased from a preoperative average of 41 points to 76 points at final followup (Noncoated Group, 70 points; Hydroxyapatite Group, 80 points). Thigh or groin pain was present in 15 patients (16 hips) (Noncoated Group, 55%; Hydroxyapatite Group, 53%). Radiographically, subsidence was the major problem at the noncoated prostheses (Noncoated Group, 91%; Hydroxyapatite Group, 5%), whereas osteolysis mainly was seen at the hydroxyapatite-coated prostheses (Noncoated Group, 18%; Hydroxyapatite Group, 89%). The obtained aseptic revision rate of 27% (Noncoated Group, 27%; Hydroxyapatite Group, 26%) is too high to use this implant in young patients. The large amounts of polyethylene wear debris generated by the bipolar system play an important role in this limited success. In the initially well-fixed hydroxyapatite-coated prostheses the sealing effect of a hydroxyapatite coating creates high concentrations of polyethylene in the limited joint space, resulting in massive proximal femoral osteolysis. Consequently, a hydroxyapatite coating introduces a new failure mechanism. Therefore, hydroxyapatite does not improve the outcome of a cementless bipolar hemiarthroplasty in the long-term.

Adolescent↗

Alveolar bone response to submerged bisphosphonate-complexed hydroxyapatite implants.

BACKGROUND: In most studies using submerged hydroxyapatite implants, maintenance of alveolar bone after tooth extraction was attempted with plain hydroxyapatite materials. However, clinical results have shown that hydroxyapatite may require biological modification with a bone resorption-inhibiting agent which may be beneficial for maintenance of alveolar bone. We conducted experimental and clinical studies to evaluate the effect of highly bisphosphonate-complexed hydroxyapatite implants on osteoconduction and repair in alveolar bone. METHODS: Porous hydroxyapatite implants were pre-incubated in 10(-2)M bisphosphonate solutions at pH 3.49. The implants had a diameter of 2.1 mm and a height of 2 mm and adsorbed 115 microg bisphosphonate. Five goats were implanted with 4 plain hydroxyapatite implants on each side of the mandible in root extraction sockets for the precision analysis of dual x-ray absorptiometry (DEXA) measurements. Ten goats were implanted with 4 bisphosphonate/hydroxyapatite implants on one side of the mandible and 4 plain hydroxyapatite implants on the opposite mandible. In a clinical study, 23 bisphosphonate/hydroxyapatite implants were placed in periodontally destroyed tooth root sockets and followed up during one year. RESULTS: The range for the bone mineral density (BMD) measurement errors for goat histologic sections was 0.48% to 1.03%. There were large differences in peri-implant BMDs in the left and right mandible of the same goat, irrespective as to whether hydroxyapatite or bisphosphonate/hydroxyapatite implants were present. This was due to local anatomical differences typical of alveolar bone. These differences were not significant. Histologically, all bisphosphonate/hydroxyapatite as well as hydroxyapatite controls appeared to be fully integrated and effective as bone replacement material in goat alveolar bone. They exhibited vascularization and osteoconduction of alveolar bone growth along and inside their porous structure. In patients peri-implant healing was clinically and radiographically comparable to plain hydroxyapatite implants. All implants were retained and no dehiscences developed. Radiographically, peri-implant radiolucencies disappeared and alveolar bone was deposited in close proximity to the implants. CONCLUSIONS: This study contributes to the understanding of the biological properties of hydroxyapatite implants as carriers for the bone-modulating agent bisphosphonate. Our study suggests that normal osteoconduction and repair occurred in alveolar bone around the highly bisphosphonate-complexed hydroxyapatite implants.

Absorptiometry, Photon↗

Effect of a ceramic and a non-ceramic hydroxyapatite on cell growth and procollagen synthesis of cultured human gingival fibroblasts.

BACKGROUND: Ceramic hydroxyapatites and non-ceramic hydroxyapatites have been used extensively as alloplastic materials for bone reconstruction. However, different forms of hydroxyapatite induce different types of tissue response. METHODS: Human gingival fibroblasts (FMM1 cells) were used to analyze ceramic and non-ceramic hydroxyapatite biocompatibility. The cells were grown on surfaces covered either by collagen (control group), collagen plus ceramic hydroxyapatite, or collagen plus non-ceramic hydroxyapatite. Scanning electron microscopy, growth and cell viability curves, and procollagen immunoprecipitation were obtained. For the growth and viability curves, 10(4) cells were seeded on 60 mm dishes. Cells from each group were counted, in triplicate, at 1, 3, 4, 5, and 6 days after seeding using the Trypan blue dye exclusion assay. RESULTS: The cells grew in close contact with both types of hydroxyapatite particles. No differences were found in the amount of procollagen synthesis among any experimental group. The cultures treated with ceramic hydroxyapatite had a growth delay for the first 5 days. There was no difference in cell viability between the control group and the non-ceramic hydroxyapatite group. However, cultures treated with ceramic hydroxyapatite showed significantly lower viability percentages than the other groups. CONCLUSIONS: Hydroxyapatite supports cell growth and fibroblast metabolism including collagen production, and hence is biocompatible. Cell viability and structural studies showed that non-ceramic hydroxyapatite has relevant physical and biological properties as an implant material.

Algorithms↗

Hydroxyapatite-coated acetabular components. Histological and histomorphometric analysis of six cups retrieved at autopsy between three and seven years after successful implantation.

BACKGROUND: Important questions remain regarding the use of hydroxyapatite-coated acetabular components in total hip arthroplasty. What is the relation of resorption of the hydroxyapatite coating to enduring fixation? Will unresorbed or dislodged hydroxyapatite particles cause adverse tissue reactions? Retrieval studies of clinically well-functioning acetabular components should help to answer these questions. METHODS: We examined six clinically successful hydroxyapatite-coated cementless acetabular components that were retrieved at autopsy between 3.3 and 6.6 years after implantation. All components were of the same design. The prostheses and the surrounding bone were prepared for qualitative histological and quantitative histomorphometric analysis. The percentage of bone growth onto the implant, the relative bone area around the implant, the extent of residual hydroxyapatite coating, and the coating thickness were measured. RESULTS: All of the cups showed bone ongrowth, with a mean bone-implant contact (and standard deviation) of 36.5% +/- 13.5%. The contact area was the same in all three zones delineated by DeLee and Charnley. The extent and thickness of the hydroxyapatite layer were much reduced in the specimens from older patients and in those associated with a longer duration of implantation. Degradation of the hydroxyapatite coating by osteoclasts was observed. We did not observe loose hydroxyapatite granules far from the coating, nor did we note any adverse tissue reaction to these granules. In contrast, polyethylene debris was noted in approximately half of the empty screw-holes. CONCLUSIONS: Cell-mediated hydroxyapatite resorption seems to be the main reason for loss of hydroxyapatite coating. The area of bone ongrowth was within a certain range (20% to 50%) of the measured surfaces, and it was independent of the amount of hydroxyapatite residue. The hydroxyapatite coating showed a slow rate of resorption with time, without any adverse tissue reactions.

Absorption↗

Proliferation and differentiation of human trabecular osteoblastic cells on hydroxyapatite.

In order to evaluate whether human osteoblastic cells differentiate normally on hydroxyapatite, we have compared the adhesion, proliferation, and differentiation of human trabecular (HT) osteoblastic cells on synthetic-dense hydroxyapatite and on standard plastic culture. We show here that initial HT cell attachment was 4-fold lower on hydroxyapatite than on plastic after 4 h of culture, and that normal cell attachment on hydroxyapatite was restored after 18 h of culture. HT cell proliferation was similar on the two substrates at 2-8 days of culture, but was lower on hydroxyapatite compared to plastic after 15 and 28 days of culture, as evaluated by DNA synthesis or cell number. HT cells cultured on both substrates produced an abundant extracellular matrix which immunostained for Type I collagen. The levels of carboxyterminal propeptide of Type I procollagen (P1CP) in the medium were lower in HT cell cultures on hydroxyapatite than on plastic. In addition, (3H)-proline incorporation into matrix proteins and the mean thickness of matrix layers were 52% and 26% lower, respectively, on hydroxyapatite compared to plastic after 4 weeks of culture, indicating that the total collagenous matrix synthesized by HT cells was lower on hydroxyapatite. However, (3H)-proline and calcium uptake expressed per cell was higher on hydroxyapatite than on plastic. The results show that human osteoblastic cells attach, proliferate, and differentiate on dense hydroxyapatite with a sequence similar to that of plastic. However, the growth of human osteoblastic cells is lower on hydroxyapatite in long-term culture, which results in a reduced amount of extracellular matrix, although matrix production per cell may be increased.

Biocompatible Materials↗

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.

Animals↗

Preliminary evaluation of hydroxyapatite cement as an augmentation device in the edentulous atrophic canine mandible.

OBJECTIVE: The purpose of this study was to answer the following two questions: (1) Can hydroxyapatite cement in combination with demineralized freeze dried bone feasibly augment the dimension of an atrophic edentulous canine mandible? (2) What is the histologic fate of an augmentation graft composed of hydroxyapatite cement and demineralized freeze dried bone placed on the surface of an atrophic edentulous canine mandible? STUDY DESIGN: Each of four mixed-breed canines (weighing 50 to 60 pounds) underwent bilateral mandibular dental extraction (canine to second molar) and radical alveolectomy. After 4 months of healing, a bilateral subperiosteal mandibular augmentation graft was put into place, with hydroxyapatite cement/demineralized freeze dried bone on the surface of one hemimandible and porous granular hydroxyapatite and demineralized freeze dried bone on the surface of the other hemimandible. The animals were killed after functioning on a soft diet for 9 months, and the grafted hemimandibles were harvested. RESULTS: Both hydroxyapatite cement and granular hydroxyapatite grafts appeared to augment the edentulous atrophic canine mandible. On histologic exam, the hydroxyapatite cement grafts showed osteoconduction and subperiosteal and endosteal osteonal bone formation, whereas the granular hydroxyapatite grafts showed only osteoconduction. Neither graft material showed chronic or acute inflammation. CONCLUSION: Hydroxyapatite cement can function feasibly as a mandibular augmentation device. The histologic fate of hydroxyapatite cement is different from that of granular hydroxyapatite. It has a fate comparable to autograft or allograft cortical bone grafts.

Alveolar Ridge Augmentation↗

The efficacy of interconnected porous hydroxyapatite in achieving posterolateral lumbar fusion in sheep.

STUDY DESIGN: An animal study was performed to evaluate lumbar spinal fusion radiologically and mechanically. OBJECTIVES: To assess the efficacy of interconnected porous hydroxyapatite in achieving posterolateral lumbar arthrodesis in sheep. SUMMARY OF BACKGROUND DATA: Posterolateral spinal arthrodesis with autologous bone graft is the gold standard procedure for lumbar fusion. The procedure for harvesting bone from the iliac crest increases morbidity. Interconnected porous hydroxyapatite has been used effectively as an alternative to cancellous bone graft material in metaphyseal bone defects. Little is known about the efficacy of interconnected porous hydroxyapatite in achieving lumbar spinal fusion. METHODS: Four groups of seven sheep underwent bisegmental posterolateral lumbar fusion with instrumentation using different intertransverse graft material. In group 1, no graft material was used. In group 2, autologous bone was used. Group 3 had interconnected porous hydroxyapatite. Group 4 had an equip of interconnected porous hydroxyapatite and autologous bone. The animals were killed at 20 weeks after surgery. Radiographs and computed tomography images were obtained. The fusion masses were graded for bone resorption and trabecular connectivity on the computed tomography images. Mechanical testing of the specimens was performed, and the three-dimensional segmental motion was measured in flexion/extension, axial rotation, and lateral bending. RESULTS: The radiographic images were difficult to interpret because of the radiodense interconnected porous hydroxyapatite granules. According to mechanical stability criteria, the fusion rate for the different groups was as follows: 100% (14/14) for the autologous bone group, 72% (10/14) for the bone/interconnected porous hydroxyapatite group, 50% (7/14) for the pure interconnected porous hydroxyapatite group, and 15% (2/14) for the sham group. CONCLUSIONS: Spinal arthrodesis using interconnected porous hydroxyapatite alone or mixed with bone as graft material reduced segmental motion. It was not, however, as effective as autologous bone graft material in achieving spinal arthrodesis. The sheep model using autologous bone achieved a 100% fusion rate. Because the nonunion rate for a single level in humans may be as high as 40%, the fusion rate with bone/interconnected porous hydroxyapatite in humans may be lower than the 72% found in the sheep model. The little resorption of the radiodense interconnected porous hydroxyapatite granules made the radiologic evaluation of the fusion masses difficult.

Animals↗

Complications related to hydroxyapatite vertebral spacer in anterior cervical spine surgery.

STUDY DESIGN: This is a report of complications related to the hydroxyapatite vertebral spacer used for anterior cervical reconstructive surgery. Compression of the spinal cord by broken fragments of hydroxyapatite spacer as well as its surrounding radiolucent clear zone were observed in seven patients. OBJECTIVES: To report complications related to the use of hydroxyapatite vertebral spacer for anterior cervical reconstructive surgery and to discuss how to prevent these complications. SUMMARY OF BACKGROUND DATA: Despite previous articles reporting the clinical applications of hydroxyapatite vertebral spacer for the cervical spine, clinical reports regarding the long-term results of hydroxyapatite spacer for anterior cervical surgery and its complications have been limited. METHODS: The authors reviewed patients who underwent anterior reconstructive surgery using the hydroxyapatite spacer at other hospitals and had postoperative complications related to hydroxyapatite spacer. RESULTS: Seven patients previously treated by anterior cervical spine surgery using the hydroxyapatite vertebral spacer were referred to the authors because of unsatisfactory surgical outcomes. All the patients had a radiolucent clear zone around the spacer and experienced severe neck pain. Four had fracture of the hydroxyapatite spacer, and two had compression of the spinal cord by retropulsed fragments of broken hydroxyapatite spacers. CONCLUSIONS: Although hydroxyapatite has been used in many medical fields because of its bioactive characteristics, its mechanical properties should be improved to lessen the risks of breakage and subsequent spinal cord compression. Gentle insertion maneuvers are also important to avoid the production of cracks inside the spacer.

Aged↗

A 1-year study of hydroxyapatite-derived biomaterials in an adult sheep model: III. Comparison with autogenous bone graft for facial augmentation.

BACKGROUND: The present study investigates onlay bone grafts and implants in a large-animal (sheep) model to determine whether there are composite biomaterials that can maximize long-term facial augmentation when compared with conventional bone grafts. METHODS: Facial augmentation was performed in 10 adult sheep. First, 16.8 x 5-mm disks were prepared from autogenous calvarial bone, hydroxyapatite ceramic, ceramic composite of 60 percent hydroxyapatite and 40 percent beta-tricalcium phosphate (60 percent hydroxyapatite ceramic), and hydroxyapatite cement paste. Facial recipient sites were the body of the mandible (depository), the maxillary region (resorptive), and the frontal bone (depository). The volume of all bone grafts and implants was determined using computed tomographic scans, and the amount of bone formation was measured by means of backscatter electron microscopy 1 year postimplantation. RESULTS: Cranial bone graft demonstrated a highly significant reduction in volume in all sites studied. Other than a slight decrease in volume of hydroxyapatite cement paste disks applied to the maxillary region, there was no significant change in volume of the biomaterials implanted in any of the remaining recipient sites. Bone replacement was greatest in hydroxyapatite ceramic (23.9 percent) followed by 60 percent hydroxyapatite ceramic (16.4 percent) and least with hydroxyapatite cement paste (4.2 percent). Minimal differences in bone replacement were noted between recipient sites. CONCLUSIONS: This study demonstrates that the volume maintenance of onlay hydroxyapatite composites is highly predictable, whereas that of cranial bone graft is unpredictable. Minimal differences were seen in bone replacement within biomaterials between "depository" and "resorptive" facial recipient sites. Ceramic forms of onlay hydroxyapatite implants demonstrated significantly greater bone replacement than did the cement paste forms of hydroxyapatite.

Animals↗

Experimental hydroxyapatite cement cranioplasty.

Hydroxyapatite cement is a calcium phosphate-based material that when mixed with water forms a dense paste that sets within 15 minutes and isothermically converts in vivo to a microporous hydroxyapatite implant. This cement was used to reconstruct bilateral 2.5-cm-diameter full-thickness critical-sized parietal skull defects in six cats. One side was reconstructed with 100 percent hydroxyapatite cement, and the other with a mixture of 50 percent hydroxyapatite cement and 50 percent ground autogenous bone by weight. These animals were sacrificed at 6 and 12 months after implantation. Positive and negative controls also were prepared. The anatomic contour of the soft tissue overlying all hydroxyapatite cement implants was well maintained, there were no wound infections or structural failures, and the implants were well tolerated histologically. None of the negative (unreconstructed) control defects was completely filled with repair bone, and all positive (methyl methacrylate) controls demonstrated foreign-body giant-cell formation and fibrous encapsulation of the implants. Examination of decalcified and undecalcified sections revealed progressive but variable replacement of the cement by new bone and soft tissue without a change in the shape or volume of the hydroxyapatite cement-reconstructed areas. New bone comprised 77.3 and 64.7 percent of the tissue replacing the hydroxyapatite cement and hydroxyapatite cement-bone implants, respectively. Replacement of the hydroxyapatite cement implants by new bone is postulated to occur by a combination of osteoconduction and implant resorption. These results indicate that further experimental research leading to the possible application of hydroxyapatite cement for full-thickness calvarial defect reconstruction in humans is warranted.

Animals↗

The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral.

The morphogenesis of bone in a porous hydroxyapatite substratum was studied after intramuscular implantation in adult primates. Replicas of porous hydroxyapatite that had been obtained after hydrothermal conversion of the calcium carbonate exoskeleton of coral (genus Goniopora) were implanted intramuscularly in twenty-four adult male baboons (Papio ursinus). Serial sections from specimens that had been harvested at three, six, and nine months showed that initially the formation of fibrous connective tissue was characterized by a prominent vascular component and by condensations of collagen fibers assembled at the interface of the hydroxyapatite. The morphogenesis of bone was intimately associated with the differentiation of the connective-tissue condensations. Bone formed without an intervening endochondral phase. Although the amount of bone varied considerably, in several specimens extensive bone developed, filling large portions of the porous spaces and culminating in total penetration by bone within the implants. The mean volume fraction composition of the specimens was 20.8 +/- 1.0 per cent (mean and standard error) for bone, 17.3 +/- 1.7 per cent for connective-tissue condensation, 31.9 +/- 1.0 per cent for fibrovascular tissue, 6.4 +/- 0.6 per cent for bone marrow, and 34.6 +/- 0.5 per cent for the hydroxyapatite framework. The amount of bone and marrow increased at each time-period, and the hydroxyapatite framework was significantly reduced between six and nine months. This indicated a moderate biodegradation over time, which was possibly a result of incomplete conversion of carbonate to hydroxyapatite. Linear regression analysis showed a negative correlation between the hydroxyapatite framework and the magnitude of bone formation within the porosities of the hydroxyapatite (p = 0.0001). Biochemical coating of the hydroxyapatite substratum with an allogeneic fibrin-fibronectin protein concentrate prepared from baboon plasma did not significantly increase the amount of bone formation within the porous spaces. The hydroxyapatite substratum may have functioned as a solid-phase domain for anchorage of bone morphogenetic proteins.

Animals↗

Aqueous formation of hydroxyapatite.

The kinetics of stoichiometric (Ca/P = 1.67) and calcium-deficient (Ca/P = 1.5) hydroxyapatite formed in aqueous solution by acid-base reactions involving CaHPO4 and Ca4(PO4)2O were determined. Complete reaction occurs within 6 h at 37.4 degrees C regardless of composition with stoichiometric hydroxyapatite forming more rapidly. Stoichiometric hydroxyapatite formed more rapidly because the particle sizes of its precursors were smaller. Hydroxyapatite formation is characterized by an initial period of surface hydration of the precursors, an induction period, and a period during which the bulk of the conversion to hydroxyapatite occurs. During the first 3 h of reaction at 37.4 degrees C, the pH is about 8.25 and 7.6, respectively, as the stoichiometric and calcium-deficient hydroxyapatite are being formed. Subsequently the pH values move toward those of the related invariant points: Ca10(PO4)6(OH)2-Ca(OH)2 solution, and CaHPO4-Ca9HPO4(PO4)5OH solution. The concentrations of calcium and phosphate in solution never exceed those in serum. Seeding with 5 wt% hydroxyapatite eliminates induction regardless of composition. The kinetics are first-order and follow the Arrhenius relationship regardless of composition. The total heats of reaction (delta Hr) were determined at constant temperatures between 25 degrees C and 70 degrees C. delta Hr values of 261.3 and 320 kJ/mol were determined for the formation of calcium-deficient hydroxyapatite and stoichiometric hydroxyapatite, respectively. Activation energies of 84.5 and 87.4 kJ/mol were calculated for the formation of calcium-deficient and stoichiometric hydroxyapatite, respectively. Heats of formation for Ca4(PO4)2O and Ca9HPO4(PO4)5OH were calculated to be -4764.1 and -12707.7 kJ/mol, respectively.

Biocompatible Materials↗

In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora.

Hydroxyapatite cement was investigated in situ for the reconstruction of juxta-articular defects. Polymethylmethacrylate is currently the most commonly used material for the reconstruction of bone defects following the exteriorization and curettage of aggressive benign tumors. In vitro, we compared the effects of hydroxyapatite cement and polymethylmethacrylate in restoring the stiffness of the subchondral plate in a caprine femoral defect model. Ten matched pairs of caprine femora underwent nondestructive compression testing normal to the load-bearing surface. A standardized subchondral defect 12 mm in diameter was created in the medial femoral condyle. Compression testing was repeated to determine the reduction in stiffness caused by the defect. Each femur from each pair was randomly assigned to one of two groups (n=9), and the defects were augmented with either polymethylmethacrylate or hydroxyapatite cement. After 12 hours, compression testing was repeated to determine the subchondral stiffness after augmentation. Compared with intact femora, the defect specimens that were later treated with either polymethylmethacrylate or hydroxyapatite cement exhibited stiffness values of 70 (386+/-107 N/mm) and 59% (343+/-94 N/mm) respectively, which represented a significant reduction in stiffness (p=0.05). Augmentation with polymethylmethacrylate or hydroxyapatite cement restored stiffness by 81 (450+/-111 N/mm) and 71% (413+/-115 N/mm), respectively, of the values of intact specimens. Hydroxyapatite cement restored stiffness significantly (p=0.05) over the stiffness of the nonaugmented defect compared with the stiffness after augmentation with polymethylmethacrylate (p=0.12). Neither polymethylmethacrylate nor hydroxyapatite cement restored stiffness to that of intact femora (p=0.05). In the current detect model, hydroxyapatite cement was comparable with polymethylmethacrylate in restoring subchondral stiffness. Unlike polymethylmethacrylate, however, hydroxyapatite cement has the following advantages: it is osteoconductive, is replaced by host bone, and avoids the potential for thermal necrosis. Hydroxyapatite cement may therefore provide a viable alternative to polymethylmethacrylate for augmentation of juxta-articular and other bone defects.

Animals↗

Size-controlled hydroxyapatite nanoparticles as self-organized organic-inorganic composite materials.

This paper presents some results concerning the size-controlled hydroxyapatite nanoparticles obtained in aqueous media in a biopolymer matrix from soluble precursors salts. Taking the inspiration from nature, where composite materials made of a polymer matrix and inorganic fillers are often found, e.g. bone, shell of crustaceans, shell of eggs, etc., the feasibility on making composite materials containing chitosan and nanosized hydroxyapatite was investigated. A stepwise co-precipitation approach was used to obtain different types of composites by means of different ratio between components. The synthesis of hydroxyapatite was carried out in the chitosan matrix from calcium chloride and sodium dihydrogenphosphate in alkaline solutions at moderate pH of 10-11 for 24 h. Our research is focused on studying and understanding the structure of this class of composites, aiming at the development of novel materials, controlled at the nanolevel scale. The X-ray diffraction technique was employed in order to study the kinetic of hydroxyapatite formation in the chitosan matrix as well as to determine the HAp crystallite sizes in the composite samples. The hydroxyapatite synthesized using this route was found to be nano-sized (15-50 nm). Moreover, applying an original approach to analyze the (002) XRD diffraction peak profile of hydroxyapatite by using a sum of two Gauss functions, the bimodal distribution of nanosized hydroxyapatite within the chitosan matrix was revealed. Two types of size distribution domains such as cluster-like (between 200 and 400 nm), which are the habitat of ''small'' hydroxyapatite nanocrystallites and scattered-like, which are the habitat of ''large'' hydroxyapatite nanocrystallites was probed by TEM and CSLM. The structural features of composites suggest that self-assembly processes might be involved. The composites contain nanosized hydroxyapatite with structural features close to those of biological apatites that make them attractive for bone tissue engineering applications.

Biocompatible Materials↗

Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro.

This study describes the characteristics of the in vitro binding and release of the anti-tumor drug cisplatin by slurries of synthetic hydroxyapatite crystals carried out in aqueous media. The adsorption of cisplatin by slurries of hydroxyapatite and its release were found to depend significantly on the ionic composition of the aqueous media used. At a constant pH of 7.4, significantly more cisplatin is adsorbed by the hydroxyapatite crystals in the slurry from a chloride-free phosphate buffered solution or a Tris buffered solution than from a buffered phosphate solution containing chloride ions. The amount of hydroxyapatite-bound cisplatin desorbed into solution was also progressively increased as a function of the increasing concentration of chloride in the equilibrating solution. Very little hydroxyapatite-bound cisplatin was released from the crystals in either a Tris or phosphate buffer. These results suggest that it is the hydrated derivatives of cisplatin which are involved in the adsorption of cisplatin by hydroxyapatite crystals. The adsorption data can be expressed as a Freundlich isotherm from which the association constant can be calculated. The rate of release of cisplatin bound to crystals of hydroxyapatite is relatively slow even at the maximum concentration of chloride ions in the phosphate buffer. Approximately 33% of the total cisplatin bound to the crystals of hydroxyapatite was released after 4.25 days. An additional 15% of the remaining cisplatin bound to the hydroxyapatite cyrstals was released after an additional equilibration with fresh buffer for two weeks (58% of the total cisplatin originally bound). These findings suggest that cisplatin bound to slurries of hydroxyapatite crystals may be useful in the local treatment of malignant tumors.

Adsorption↗

A randomized trial of hydroxyapatite coated prostheses in total hip arthroplasty.

In a prospective randomized trial, 62 consecutive primary cementless total hip arthroplasties in 55 patients were performed by one surgeon using either hydroxyapatite coated (35 hips) or nonhydroxyapatite coated femoral prostheses (27 hips). The dual tapered femoral stem had a Ti-6AI-4V plasma sprayed circumferential proximal porous coat applied to the proximal 1/3 of the stem. The middle 1/3 had a roughened blasted textured surface, and the distal 1/3 had a smooth surface. The hydroxyapatite coated femoral stems had an additional hydroxyapatite coating applied to the proximal porous coat with use of an air plasma process. The patients in the two groups were not significantly different regarding age (48.2 +/- 9.0 years hydroxyapatite group, 50.4 +/- 8.7 years control group), gender, Charnley class, or length of followup (4.4 +/- 0.7 years hydroxyapatite group, 4.9 +/- 1.0 years control group). Forty-nine patients (54 hips) were available for clinical followup, and 45 patients (50 hips) had radiographic followup. A minimum 3-year followup was recorded. To date, there have been no femoral prostheses failures. No femoral implant has migrated or subsided. Radiographically, the hydroxyapatite coated stems showed trends toward increased distal stem related cortical hypertrophy, increased cancellous condensation and less endosteal cavitation. Two nonhydroxyapatite coated stems had distal endosteal cavitation, whereas no hydroxyapatite coated stems did. There were two cases of acetabular osteolysis (revision in one) and two cases of acetabular cup migration (nonrevised), all occurring in the control group. The overall revision rate was 4%. There was no difference in Harris hip scores at 6 months (80.6 +/- 13.0 points hydroxyapatite group, 83.8 +/- 12.4 points control group) or at last followup (85.6 +/- 15.4 points hydroxyapatite group, 89.7 +/- 13.4 control group). The Harris hip pain scores also were not significantly different at 6 months or at last followup. Multiple linear regression analysis controlling for age, gender, and length of followup revealed no significant predictors of Harris hip or pain scores. The results of this study at an average of 4.6 years do not indicate a significant clinical advantage to the use of hydroxyapatite coated femoral prostheses in primary cementless total hip arthroplasty when judged by the criteria of Harris hip scores and femoral stem survivorship.

Acetabulum↗

Bone differentiation in porous hydroxyapatite in baboons is regulated by the geometry of the substratum: implications for reconstructive craniofacial surgery.

Previous studies have shown the morphogenesis of bone in a porous hydroxyapatite substratum when implanted intramuscularly in baboons. This hydroxyapatite-induced osteogenesis model was used to study the effect of geometry and pore size of the substratum on bone differentiation. Two distinct geometric configurations of porous hydroxyapatite of different pore size were obtained after hydrothermal conversion of the calcium carbonate exoskeleton of corals (genera Porites and Goniopora). Substrata were blocks of hydroxyapatite in rod configuration of 200- and 500-microns pore size and granular hydroxyapatite (400 to 620 microns in diameter) of 200- and 500-microns pore size. A total of 64 granular hydroxyapatite implants and 32 hydroxyapatite rods were implanted intramuscularly in 8 subadult male baboons (Papio ursinus). Specimens were harvested on days 60 and 90 and subjected to histologic and histomorphometric analysis. With the exception of an island of bone that formed in two implants of granular hydroxyapatite of 500-microns pore size, bone differentiation occurred only in blocks of hydroxyapatite in rod configuration of either pore size at both observation periods. The lack of bone formation in the granular hydroxyapatite indicates the critical role of geometry of the substratum in bone differentiation. These results in primates may have implications for the appropriate selection of porous bone substitutes for reconstructive craniofacial surgery in humans.

Animals↗