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The compression strength of the lumbar spine reinforced by newly developed hydroxyapatite (HA) bone cement was evaluated using a mechanical testing machine. Sixteen cadaveric lumbar vertebrae obtained from nine subjects (five men, four women) were used. The specimens were randomly divided into two groups. In group A ( n = 8), HA bone cement was injected into the vertebral body through curetted pedicles using specially designed needles and then pushed into the vertebral body by the surgeon's finger, simulating open surgery. In group B ( n = 8) the cement was injected using 16-gauge Ostycut biopsy needles via the pedicles through both sides, simulating percutaneous injection. The initial ultimate compression strength of the specimens was 28.6 +/- 13.4 MPa in group A and 25.2 +/- 12.6 MPa in group B. The value after reinforcement was 35.6 +/- 12.9 MPa in group A and 30.4 +/- 14.8 MPa in group B. There was no significant difference between the ultimate strength of the intact specimen and that after reinforcement. The present study demonstrated biomechanical characteristics of vertebral body fractures reinforced with newly developed HA bone cement.

Study Design: Transpedicular lumbar interbody fusion (TLIF) was performed in a sheep model comparing three treatment groups: a composite of osteogenic protein (OP)-1 and hydroxyapatite carrier (HA), HA without OP-1, and autograft., Objective: To evaluate the efficacy of the composite of OP-1 and HA (HA-OP-1) in achieving reliable TLIF., Summary of Background Data: Anterior fusion techniques directly address disc-related problems and achieve primary axial stability. However, they are characterized by high morbidity. Alternatively, the theoretically advantageous posterior TLIF technique using autograft fails clinically because it lacks compressive stability., Methods: In 36 sheep, lumbar vertebrae L4 to L6 were instrumented posteriorly. Endoscopically assisted TLIF of L4 to L5 was performed. In 12 sheep, the defect was filled with injectable HA-OP-1. Another 12 sheep were treated with HA and another 12 with autograft. Animals were killed at 8 weeks and evaluated by radiologic, histologic, and histomorphometric analysis and by fluorochrome labeling., Results: Only 10 autograft sheep were available for evaluation. Radiologically and histologically, TLIF with HA-OP-1 led to a fusion rate of 10 in 12 compared with autograft (one in 10 fused) and HA (two in 12 fused) ( = 0.0016). Semiquantitative radiologic and histologic scoring also revealed significant differences with superiority of HA-OP-1 ( = 0.0011). Compared with HA, HA-OP-1 presented significantly more ossification at the bone-cement interface ( = 0.0003) and less cement resorption ( = 0.0209). In four of 12 HA sheep, excessive resorption was responsible for local aseptic inflammation., Conclusions: Biointegration of the osteoconductive HA does not occur, because shear forces cause early HA fracture, subsequent fragmentation, and gross resorption (initiating severe inflammation in four of 12 sheep). In contrast, osteoinductive effects of HA-OP-1 enable bio-integration, resulting in full osseous composite sheathing and solid fusion. By use of this composite, TLIF is successfully applied in sheep. Harvesting autograft and the anterior approach are avoided.

On purpose to achieve better and more controlled alveolar ridge augmentation, biodegradable polyglycolide (PGA) curved implants with porous, particulate hydroxylapatite (HA) were developed to be used in an experimental augmentation in sheep mandible. Prior to surgery curved PGA implants were loaded with particulate HA with help of a rather fast degrading adhesive, polyglycolide/polylactide (PGA/PLA) copolymer. This augmentation device was inserted into the ridge using a slight modification of the tunnelling technique. Macroscopically, a dehiscence with loss of HA particles was observed in 3 of the 16 augmentations. Bone ingrowth was seen in a noticeable degree in one sheep at 24 weeks. Instead, foreign body-type cells were shown at the interface of mandibular bone and hydroxylapatite deposit, as well as abundant connective tissue reaction inside HA deposits. The results of the study give rise to concern about bony integration in the presence of biodegradable polyglycolide substances in HA augmentation. The findings call in question even their use as a carrier for bone forming agents in combination with HA.

Study Design: A rabbit and rhesus monkey model of posterolateral intertransverse process spine arthrodesis was used., Objective: To test two new soft tissue compression resistant ceramic/collagen sponge carriers for recombinant human bone morphogenetic protein-2., Summary of Background Data: After determining that a plain collagen sponge was too compressible for large animals in a posterolateral fusion application, the authors demonstrated good bone induction using biphasic ceramic phosphate granules (60% hydroxyapatite/40% tricalcium phosphate) as the carrier matrix for recombinant human bone morphogenetic protein 2 in rhesus monkeys. A limitation of 60:40 biphasic ceramic phosphate was its slow resorption time caused by the high hydroxyapatite content, making radiographic detection of new bone formation very difficult., Methods: Adult New Zealand white rabbits (n = 14) underwent posterolateral spine arthrodesis at L5-L6 using 5:95 biphasic ceramic phosphate (5% hydroxyapatite/95% tricalcium phosphate) impregnated Type I collagen sponges (17 x 35 x 2.5 mm, two per side) loaded with 0.86 mg recombinant human bone morphogenetic protein 2. Additional rabbits (n = 14) received 60:40 hydroxyapatite-tricalcium phosphate granules as the carrier for bone morphogenetic protein 2. Adult rhesus monkeys (n = 6) underwent posterolateral arthrodesis at L4-L5 with ceramic/collagen sponge carrier loaded with 9 mg recombinant human bone morphogenetic protein 2 per side. Two monkeys received ceramic/collagen sponges containing 15:85 biphasic ceramic phosphate (15% hydroxyapatite/85% tricalcium phosphate) with two pieces per side; two received sponges containing 5:95 biphasic ceramic phosphate with two pieces per side, and two received sponges containing 5:95 biphasic ceramic phosphate with four pieces per side. The rabbits were killed after 5 weeks and the monkeys after 24 weeks; the spines were evaluated by manual palpation, radiographs, tensile mechanical testing (rabbits only), and histology., Results: The recombinant human bone morphogenetic protein 2 delivered in the 5:95 biphasic ceramic phosphate/collagen sponge achieved fusion in 100% of rabbits and had improved handling properties compared with the biphasic ceramic phosphate granules. Biomechanical results with 5:95 biphasic ceramic phosphate/collagen carrier were comparable to those obtained with the 60:40 biphasic ceramic phosphate granules and superior to those of autogenous bone graft (P < 0.05). The recombinant human bone morphogenetic protein 2 delivered in the 15:85 or the 5:95 biphasic ceramic phosphate/collagen sponge carrier (two pieces per side) induced fusion in nonhuman primates with normal bone histology, less residual ceramic, and more bone in the center of the carrier matrix in comparison with BCO granules alone. The 15:85 biphasic ceramic phosphate/collagen sponge resulted in fusion mass sizes closer to the original size of the matrix implanted than did the 5:95 biphasic ceramic phosphate/collagen sponge, which was considered a desirable feature. The monkeys with 9 mg recombinant human bone morphogenetic protein 2 spread over four sponges per side instead of two had half the effective recombinant human bone morphogenetic protein 2 concentration per sponge and inferior results., Conclusions: The new compression-resistant biphasic ceramic phosphate/collagen sponge matrices were biologically compatible with recombinant human bone morphogenetic protein 2 bone formation, resulted in biomechanically stiffer fusion masses than autograft, better space maintenance than plain collagen sponges, and improved handling and radiographic resorption properties over the ceramic carriers previously tested.

In this study, we hypothesize that loading more marrow-derived mesenchymal stem cells (MSCs) into porous material by using a low-pressure system during subculture, creating a composite which combines MSCs and a novel mechanical reinforced porous hydroxyapatite, can result in more bone tissue formation in vivo. Within 26 weeks postimplantation, we examined in vivo bone formation of the experimental group with 100 mmHg pressure applied to porous HA blocks loaded with MSCs. For in vivo testing, the 2-week subcultured HA/MSC composites were implanted into subcutaneous sites of syngeneic rats. These implants were harvested at 13 and 26 weeks after implantation. SEM showed that the pore surface is covered by osteoblasts as well as collagenous extracellular matrix at 13 weeks. Light microscopy revealed the quantity of bone at 26 weeks was greater than at 13 weeks. These results showed that the novel mechanical reinforced porous HA combined with MSC has more potential for bone formation at 100 mmHg, making this method very efficient for bone reconstruction.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

The possibility of application of HA-BIOCER synthetic hydroxyapatite in the treatment of enamel hypoplasia in children and adolescents manifested by mineralisation disorders, enamel underdevelopment, enamel deficiency and oversensitivity to mechanical, thermal and chemical stimuli was evaluated. The possibility of applying the same preparation in case of enamel fractures and teeth injuries type I according to Ellis was also examined. It was found that the application of hydroxyapatite stimulates processes of remineralization in decalcified places. It also causes removal of tooth oversensitivity to thermal and mechanical stimuli by closing open dentinal tubules or decrease in their size. HA-BIOCER preparation brings about smoothing and lighting of hypoplastic foci, improves aesthetic appearance and is not toxic to patients.

Selective drug delivery to any organ becomes very important in certain diseases and clinical manifestations, especially when the drug affects other exposed tissues adversely. The importance of selective drug action is still further increased when the affected part is poorly perfused. Although a network of blood vessels is present throughout skeletal tissue (or bone), it is not sufficient for immediate delivery of drugs to the desired site of action in the tissue and in sufficient amounts over appropriate time periods. Hence, selective drug delivery to the skeletal system has remained a great challenge to pharmaceutical scientists over the years. However, in the recent past, attention has been focused on the importance of skeletal drug delivery and the first Skeletal Drug Delivery System (SDDS) was introduced by Bucholz and Engelbrecht in 1970 for the delivery of drugs to skeletal tissues at a high concentration to achieve desirable therapeutic effects. SDDS is used to deliver the drug directly to skeletal tissue through self-setting cement, which also acts as a bone filler, thereby improving the therapeutic effectiveness of drugs in bone diseases. The present review highlights the applicability of various materials as bone fillers for the purpose of skeletal drug delivery.

Background: A great deal of interest has been focused on finding substitutes for autogenous bone grafts. Among the most interesting materials are different calcium phosphate compositions (e.g., hydroxyapatite [HA]), due to their biocompatible properties in hard and soft tissue., Purpose: The bone response to porous ceramic HA granules in combination with two lipid and one polysaccharide carrier was evaluated in an experimental bone defect model in rabbits., Materials and Methods: Circular defects (Ø 4 mm) were made in both tibias of 32 rabbits. The 64 defects were divided into four groups. Group A was augmented with a composite of HA granules and a phospholipid-diacetyl-glycerol carrier, group B with HA granules and a phospholipid carrier, group C received HA granules and a sodium hyaluronan carrier, and group D served as control. The animals were killed after 6 weeks and ground sections were evaluated using light microscopic morphometry. X-ray microfluorescence (XRF) was applied in order to evaluate the suitability of this method to examine bone-biomaterial interfaces. Calcium distribution was studied using x-ray fluorescence line scans at selected interface regions of two sections in group B., Results: The HA/phospholipid composites were easier to shape and handle than the HA/hyaluronan composite. Group A had 36% newly formed bone area within the defect. Groups B and C showed significantly more newly formed bone within the defect (47% and 49%, respectively) compared to the control group (31%). The XRF analysis revealed that the amount of calcium in the newly formed bone was similar to that observed for the HA granules and slightly lower when compared to the mature, lamellar bone., Conclusions: Synchrotron radiation may be a new, suitable technique to study the interface between bone and biomaterials with regard to mineral content. The results suggest that HA granule/lipid and HA granule/hyaluronan composites have interesting properties as bone-substitute materials.

Dental plaque fluid is normally supersaturated with respect to enamel mineral but this may change to a state of undersaturation when plaque pH falls following sugar exposure, placing the adjacent enamel at risk of caries. We have determined the saturation status of the fluid in both resting and fermenting plaque following mineral supplementation. Eleven subjects abstained from oral hygiene and rinsed their mouth 3 times/d for 3 d with a placebo solution or with test solutions designed to enrich plaque with hydroxyapatite or fluorhydroxyapatite. On the morning of day 4, plaque samples were collected before and after exposure to 10% sucrose. Compared to the placebo, use of the test rinses resulted in significantly higher concentrations of Ca, P and F in plaque residue. In plaque fluid, higher post-sucrose Ca2+ free concentrations and saturation levels with respect to enamel mineral and fluorapatite were found after use of the hydroxyapatite rinse compared to the placebo, effects that probably resulted from the release of cell-bound Ca2+ as well as from the dissolution of apatite. Thus, some evidence was obtained that the test mouthrinses can counteract the fall in saturation level found when plaque is exposed briefly to sucrose. Potential long-term benefits of the test mouthrinses deserve further study.

Objective: To evaluate whether the addition of an ossein-hydroxyapatite compound (OHC) may improve the effect of hormone replacement therapy (HRT) on postmenopausal bone loss., Study Design: Of the 118 recent surgically postmenopausal women initially selected for this open study, 96 completed one-year follow-up. Patients were allocated into four groups. The first group received 50 micrograms/d of transdermal 17-beta estradiol continuously (group E, n = 23), the second received 3.32 g/d of an OHC every day (group OHC, n = 23), the third received 50 micrograms/d of transdermal 17-beta estradiol continuously plus 3.32 g/d of the OHC every day (group E-OHC, n = 26), and an additional 24 women were used as untreated controls (group C). Bone mass, assessed by dual x-ray absorptiometry, was measured prior to and at the end of treatment. Samples, including serum calcium, phosphate and osteocalcine level, were collected before therapy and during the 6th and 12th treatment months., Results: All treatment groups showed an increase in bone mineral content. This increase was higher in the E-OHC group (4.7%, P < .01). Concomitant biochemical effects at 6 and 12 months were compatible with the observed effects on bone mineral., Conclusion: The combined regimen of OHC and HRT increased vertebral bone mass in postmenopausal women to a greater extent than did OHC or HRT alone, suggesting that this drug combination may be useful in the management of postmenopausal bone loss.

Calcium hydroxyapatite (HA) ceramics are widely used in orthopaedic surgery and are known to be biocompatible, biodegradable, and osteoinductive. Recent studies of HA have identified early stage inflammatory reactions and third-body wear following hip replacement surgery. The aim of this study was to investigate the early stage inflammatory response toward HA by means of conventional radiography, histopathology, and scanning electron microscopy (SEM). HA was implanted into the medullary area of the tibiae of rabbits and followed from one week to six months. Radiography revealed local osteoporosis on Week 6 and Month 6 in some, but not, all rabbits. SEM presented favorable bonding between the implant and the cortical bone. Eosinophilic deposition, non-specific local inflammation, and bone marrow depletion were the histopathological findings. Multinuclear cells were identified in the inflammation area. Although bone ingrowth into the pores of the HA was demonstrated, there is no doubt that HA may cause an early inflammatory reaction in the bone marrow. This inflammatory reaction is followed by bone marrow depletion and may be the early sign and the cause of HA-coated implant failure.

Spontaneous mammary tumourigenesis in a high mammary tumour strain of SHN virgin mice was inhibited by the chronic ingestion of a diet containing hydroxyapatite [HAP: Ca5(OH)(PO4)3] at 2.5% or 5% up to 7 months of treatments, while not thereafter. The decrease in the excretion of urinary component levels associated with mammary tumour development was prevented in the experimental group given HAP, which resulted in the higher component levels in the experimental group than in the control of the tumourous mice. The treatment little affected body weight change, the pattern of the oestrous cycle, endocrine organ weights, glucose tolerance, serum levels of glucose and free fatty acid and serum superoxide dismutase activity. The results suggest that the inhibition by HAP of mammary tumourigenesis is at least partly ascribed to its prevention of a decreased metabolic turnover as reflected by the higher excretion of urinary components in tumourous mice given HAP.

In the quest for bioinert, easily applicable, and individually adaptable alloplastic materials, hydroxyapatite (HA) has gained a new application in onlay craniofacial augmentation. On the basis of clinical and experimental proof that intraosseous translocation of HA occurs after HA onlay augmentation, we conducted an animal study on 16 adult Goettingen minipigs in which HA, as blocks or granular, was implanted for a maximum time of 72 weeks. Our aim was to study the difference between periosteal and subperiosteal onlay augmentation of two different HA forms by comparing HA-bone interface on the intact frontal bone treated with a block form of HA versus granular HA, with special emphasis on the periosteum. Within a few weeks after subperiosteal augmentation, subimplant changes in the grafted bone became evident to such an extent that within 72 weeks the granules migrated into the frontal sinus. In contrast, in epiperiosteal HA onlay augmentation, no intraosseous migration of HA particles was observed, regardless of the type of HA implants. The HA particles were integrated within the connective tissue, and the connective tissue infiltrated the interstitial spaces. For the most part, the location and the shape of the implant remained stable. The periosteum assumed the function of a limiting membrane. We recommend that epiperiosteal onlay augmentation with HA be performed only if previous studies have proven that shape and location are stable. The periosteum should be preserved because it functions as a limiting membrane, retaining the HA and preventing it from migrating into the subimplant bone.

A drug composition LINCOGAP is assessed, consisting of lincomycin hydrochloride (33%), ultrahighly dispersed hydroxyapatite (HA) (33%), gelatin (7%), and water (27%). Distribution of tritium-labeled lincomycin in organs and tissues of experimental animals was studied by the radiometric method after implantation of the composition into a standard rat mandibular defect. Lincomycin concentration surpassing by orders of magnitude the minimal inhibitory concentration for the main lincomycin-sensitive microorganisms persisted at the site of implantation of the composition for at least 7 days, while the concentration in internal organs and tissues was the minimum. Microbiological findings indicate active diffusion of lincomycin from the site of injection into the adjacent bone. Thus, LINCOGAP exerts an antibacterial effect in the pathological focus while its general toxic effect is low and, therefore, side effects are minimized. Combination of the antibiotic with ultrahighly dispersed HA helps regulate the process of bone repair, stimulating the proliferative and functional activity of osteoblasts. Hence, combined drug LINCOGAP is a promising agent for the treatment of inflammatory destructive diseases of osseous tissue.

Hydroxyapatite (HA) granules of 100 to 300 microm, 0.9 to 1.2 mm and 3.0 to 5.0 mm were mixed in a ratio of 10:45:45 and packed into massive bone deficiencies in revision operations for total hip arthroplasty. We did not use additional graft or cup support for deficiencies of the lateral and medial wall. The procedure was carried out in 40 hips between 1986 and 1992. The radiographic spaces seen at the interface between HA and bone immediately after surgery disappeared within three months. Some spaces appeared between HA granules near the bone in the lateral part of two joints, and three sockets migrated in patients with severe segmental and cavitary deficiencies. Direct bonding of HA to bone was observed radiologically without morphological changes, except in the three joints with migration. All patients could walk without pain but the three with definite loosening needed crutches.

The purpose of this in vitro study was to evaluate the effects of acidulated calcifying fluids (CF) on remineralization of caries-like lesions of enamel. Lesions were created in sound enamel using an acidified gel. Central longitudinal sections were taken from each tooth (N = 20) following lesion formation to serve as control lesions (CL). Each tooth was sectioned into quarters and each quarter was assigned to one of four groups: 1) 1 mM calcium CF at pH 7.0 (CF1); 2) 1 mM calcium CF at pH 5.0 (ACF1); 3) 3 mM calcium CF at pH 7.0 (CF3); 4) 3 mM calcium CF at pH 5.0 (ACF3). Tooth quarters were treated with assigned CFs (HAP [Ca/P = 1.63], pH 7.0 or 5.0, 0.05 mM Fl) for ten 60-sec periods. Longitudinal sections were prepared and imbibed in water for polarized light study. Mean lesion depths were determined and compared (ANOVA and DMR). With 1 mM calcium CFs, mean lesion depths were 187 microns for CL, 154 microns for CF1 and 133 microns for ACF1. With 3 mM calcium CFs, mean lesion depths were 192 microns for CL, 172 for CF3 and 149 for ACF3. Acidulated (22%, 29%) and nonacidulated (10%, 18%) CFs resulted in significant reductions (P < 0.05) in lesion depths when compared with control lesions. Acidulated CFs (13%, 14%) resulted in significant lesion depth reductions (P < 0.05) when compared with nonacidulated CFs. The acidulated 1 mM calcium CF produced the greatest degree of remineralization. Acidulation of CFs enhanced the degree of remineralization over that attained by nonacidulated CFs. This improvement in remineralizing ability of acidulated calcifying fluids may be due to creation of a more reactive enamel surface.

The effects of an hydrosoluble fraction of the bovine bone extract Ossopan on cultured murine osteoblasts were assessed in this study. The hydrosoluble fraction from Ossopan, obtained by acid/ethanol extraction, contained significant amounts of TGF-beta 1. Calvariae from new-born rats were cultured for 1 month in synthetic medium (DMEM) supplemented with 10% fetal calf serum to allow cell proliferation; immunocytochemistry studies performed with a rabbit serum raised against alkaline phosphatase indicated that only osteoblasts were present in cell cultures. Using an XTT-based colorimetric cell proliferation assay, we showed that the hydrosoluble fraction of the bovine bone extract dose-dependently reduced the proliferation of cultured osteoblasts. A similar inhibition was obtained with a recombinant TGF-beta 1. Thus, the inhibitory effect of the hydrosoluble fraction of Ossopan on osteoblast proliferation should be due to the cytokines contained in this preparation.

Hydroxyapatite-sol was prepared by dispersing hydroxyapatite microcrystals into saline. The hydroxyapatite microcrystals were synthesized by neutralization reaction of calcium hydroxide suspension and phosphoric acid solution. Sizes of the hydroxyapatite microcrystals were less than 0.1 microns, and the mean value was 0.05 microm. The 0.2 ml hydroxyapatite-sol with a concentration of 14.8 mg/ml was injected into medullary cavities of rat femurs. Both sintered hydroxyapatite powder suspension and saline as comparative materials were injected into the medullary cavities in the same way. Reaction of the hydroxyapatite-sol in the bone medullary cavities was investigated histologically using light and transmission electron microscopes. After 3 days, new bone formation was observed by injection of hydroxyapatite-sol, while no bone formation was observed by injection of sintered hydroxyapatite powder and saline. Osteoblasts were observed endocytosing the hydroxyapatite-sol in the medullary cavities of the rats. Macrophages and undifferentiated osteoblasts were found around the hydroxyapatite-sol aggregation by transmission electron microscope. After 5 days, amounts of new bone increased and matured, forming trabeculae. Many osteoblasts were observed in a line along the surface of the bone. On the other hand, 5 days after injection of sintered hydroxyapatite powder and saline to bone formation was observed while at 10 days after injection, some immature new bone formation started to be observed. New bone increased and matured at 15 days postoperatively. From these results, it was concluded that hydroxyapatite-sol only quickly promotes the formation of new bone in bone marrow and can be used as injection liquid of new biomaterials for bone formation.

Self-setting apatite cement (apatite cement) with a phase of hydroxyapatite (HAP) was employed as a delivery system for bone morphogenetic protein (BMP). A composite of BMP and apatite cement (BMP/HAP composite) was implanted both in thigh muscle and surgically created defect of a critical size of 5 mm, which is a size that does not heal spontaneously in the femur of mice, to evaluate its osteogenetic potential as an augmentation and reconstructive material for clinical usage. The histological and immunohistochemical assessment of proteoglycans reiterated osteogenesis in the muscle tissue. On day 14 postimplantation of BMP/HAP composite, chondroid tissue was formed in the muscle, and HAP particles were seen in newly formed chondroid tissue. On the 21st day, endo-chondral ossification had occurred, however, small HAP particles remained in the newly formed bone, i.e., HAP particles and newly formed osseous tissues coexisted in a central area. BMP/HAP composite was incorporated by newly formed osseous tissue in the experimented animals. HAP particle found in BMP/HAP composite implanted into the bone defect was resorbed and replaced by osseous tissue. The apatite cement was proved to have advantages for its shaping as well as collapsing properties, and thus, apatite cement containing BMP is suggested as a favorable augmentation material in clinical usage for delivery system of BMP.

Hydroxylapatite and tricalcium phosphate are bioactive ceramic materials resembling the mineral matrix of bone. Implants have been used for the reconstruction of the posterior auditory canal wall and the ossicular chain. In this report the application of macroporous biphasic calcium phosphate implants for the reconstruction of defects in the anterior skull base is described. A mixture of granules of tricalcium phosphate and hydroxylapatite (Triosite, Xomed-Zimmer Inc) and two-component fibrin adhesive (Tissucol, Immuno AG Wien) is used. The technique is presented in detail and preliminary results are discussed.