In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite.

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated by attenuated reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Calcium deposition, osteocalcin production, and expression of osteoblast genes were significantly higher in rat bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells seeded on uncoated titanium. Implantation into rat femurs also showed that the FHA-coated material had superior osteoinductive and osseointegration activity in comparison with that of traditional implants, as assessed by microcomputed tomography and histology. Thus, titanium coated with FHA holds promise as a dental implant material.

Genotoxicity assessment of biphasic calcium phosphate of modified porosity on human dental pulp cells using Ames and Comet assays.

Biphasic Calcium Phosphate (BCP) with a ratio of 20/80 Hydroxyapatite (HA)/Beta-tricalcium phosphate (ß-TCP) promotes the differentiation of human dental pulp cells (HDPCs). In the current study, the genotoxicity of locally produced BCP of modified porosity (65%) with a mean pore size of 300micrometer (µm) was assessed using Comet and Ames assays. HDPCs were treated with BCP extract at three different inhibitory concentrations which were obtained based on cytotoxicity test conducted with concurrent negative and positive controls. The tail moment of HDPCs treated with BCP extract at all three concentrations showed no significant difference compared to negative control (p>0.05), indicating that BCP did not induce DNA damage to HDPCs. The BCP was evaluated using five tester strains of Salmonella typhimurium TA98, TA100, TA102, TA1537 and TA1538. Each strain was incubated with BCP extract with five different concentrations in the presence and absence of metabolic activation system (S9) mix. Concurrently, negative and positive controls were included. The average number of revertant colonies per plate treated with the BCP extract was less than double as compared to the number of revertant colonies in negative control plate and no dose-related increase was observed. Results from both assays suggested that the BCP of modified porosity did not exhibit any genotoxic effect under the present test conditions.

Hydroxyapatite cement cranioplasty following translabyrinthine approach: Long-term study of 369 cases.

OBJECTIVE: To report the authors' experience with hydroxyapatite cement (HAC) cranioplasty and analyze the material's long-term safety and efficacy in repairing translabyrinthine skull-base defects by examining adverse events, specifically cerebrospinal fluid (CSF) leaks and surgical site infections. STUDY DESIGN: Retrospective case-control study (primary study arm); prospective cross-sectional study of patients not examined within the last 5 years (secondary arm). SETTING: tertiary-care neurotology private practice and academic practice (two centers). METHODS: Hydroxyapatite cement implanted following translabyrinthine approach, with or without fat graft, was included. Combined approaches were excluded. Implant-associated adverse events were defined as 1) CSF leaks requiring reoperation or spinal drainage, and (2) infections requiring reoperation. Patients not examined within 5 years were interviewed by telephone to update their condition. Incidence of adverse events was compared to published data for translabyrinthine cranioplasty using fat graft alone. Implant survival analysis was performed. RESULTS: The study cohort included 369 HAC implants in the same number of patients. There were seven CSF leaks and seven infections. Combined (n = 14) incidence of adverse events was 3.8% (2.09%, 6.28%). Compared to fat graft alone, the adverse events associated with HAC were fewer (P < 0.001). Up to 15 years (5,475 days), HAC cement maintained 95% adverse event-free survival. There were no cases of meningitis. CONCLUSION: Cranioplasty using HAC with autologous fat following translabyrinthine skull-base surgery is safer and more effective than fat graft alone, up to 15 years after surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2120-2125, 2017.

Is structural hydroxyapatite tricalcium-phosphate graft or tricortical iliac crest autograft better for calcaneal lengthening osteotomy in childhood? interim results from a randomised, controlled non-inferiority study.

AIMS: To compare the structural durability of hydroxyapatite-tricalcium phosphate (HATCP) to autologous iliac crest bone graft in calcaneal lengthening osteotomy (CLO) for pes planovalgus in childhood. PATIENTS AND METHODS: We present the interim results of ten patients (HATCP, n = 6 and autograft, n = 5) with a mean age of 11.5 years (8.2 to 14.2) from a randomised controlled non-inferiority trial with six months follow-up. The primary outcome was the stability of the osteotomy as measured by radiostereometric analysis. A non-inferiority margin of ≤ 2 mm osteotomy compression was set. RESULTS: At six months the data showed that the osteotomy had been compressed by a mean 1.97 mm (99.8% confidence interval -1.65 to 5.60) more in the HATCP group than in the autograft group. Migration of the CLO grafted with HATCP stabilised at six months rather than at six weeks with autograft. CONCLUSION: This is the first randomised trial to compare the efficacy of HATCP graft with autograft in terms of stability of CLO in children. Because of problems with the HATCP the trial was stopped. We do not recommend HATCP graft in its current structure for use in unfixed CLOs. Cite this article: Bone Joint J 2016;98-B:1554-62.

Comparison of the Potential Discoloration Effect of Bioaggregate, Biodentine, and White Mineral Trioxide Aggregate on Bovine Teeth: In Vitro Research.

INTRODUCTION: Tricalcium silicate cements can be used for pulp capping, pulpotomies, apical barrier formation in teeth with open apices, repair of root perforations, regenerative endodontics, and root canal filling. The aim of this study was to evaluate and compare the discoloration potential of 3 different tricalcium cements using a bovine tooth model. METHODS: Forty bovine anterior teeth have been used for the study. Crowns separated from the roots were randomly divided into 4 groups: the BioAggregate (IBC, Vancouver, Canada) group, the Biodentine (Septodont, Saint Maur des Fosses, France) group, the mineral trioxide aggregate Angelus (Angelus, Londrina, PR, Brazil) group, and the only blood group. Materials have been placed to the standardized cavities on the lingual surfaces of the crowns, and their contact with blood has been provided. The color values of the samples were measured with a digital tooth shade determinator (VITA Easyshade; VITA Zahnfabrik, Bad Sackingen, Germany) before the placement of the materials, after the placement of the materials, in the 24th hour, in the first week, in the first month, in the third month, and in the first year. The mean value of all groups was compared using the Tukey multiple comparison test (α = 0.05). RESULTS: All groups displayed increasing discoloration during a period of the first year. The "only blood group" showed the highest color change values, and it was followed as BioAggregate, mineral trioxide aggregate Angelus, and Biodentine, respectively. Statistically significant differences were found for Biodentine when compared with the only blood and BioAggregate groups (P < .05). CONCLUSIONS: Considering the results of the study, Biodentine is found to have the least discoloration potential among the tested materials.

Hydroxyapatite deposition disease around the hip: outcomes of CT-guided treatment.

PURPOSE: Hydroxyapatite deposition disease (HADD) around the hip joint is a self-limiting condition usually treated conservatively. The aim of the present study is to directly compare the outcomes of CT-guided and conservative treatments in cases of refractory hip HADD. METHODS: Two groups of patients with refractory hip HADD were prospectively constructed from a pool of 484 patients referred for greater trochanter pain syndrome, based on the presence of calcifications around the hip and the failure of conservative treatment. Study group included 22 hips, which underwent CT-guided barbotage and steroid injection treatment, whereas control group consisted of 28 hips that were treated conservatively. Evaluation of the outcome of both groups was performed over a one-year follow-up period with the use of a score measuring clinical improvement in terms of pain and functional impairment. RESULTS: Three weeks after the initiation of treatment, study group exhibited significantly higher scores compared with the control group (P < 0.001). Improvement scores of the control group were similar to the study group after three months of treatment (P > 0.1). CONCLUSION: CT-guided treatment provides relief of debilitating symptoms in the acute phase.

Dislodgement resistance of calcium silicate-based materials from root canals with varying thickness of dentine.

AIM: To evaluate the dislodgement resistance of DiaRoot BioAggregate and Biodentine from canals in roots with varying amounts of remaining dentine thickness. METHODOLOGY: A total of 90 maxillary incisor teeth with similar dimensions were used. The teeth were extracted for periodontal reasons from adult subjects aged between 52 and 61 years. They were decoronated at the cemento-enamel junction. Simulated internal cavities with a depth of 3 mm were performed by widening the canals on the coronal thirds of the roots, leaving varying amounts of remaining dentine thickness. The canals were enlarged progressively using round diamond burs until the desired dentine wall thickness was obtained. The samples were divided into three main groups (n = 30 each) according to the dentine thickness as follows: group 1: dentine thickness of 0.75 mm, group 2: dentine thickness of 1.50 mm and group 3: dentine thickness of 2.25 mm. Then, these main groups were further divided into two subgroups (n = 15 each) according to the filling material (DiaRoot BioAggregate or Biodentine). Horizontal root slices of 1 mm were obtained from each specimen. Vertical loading was applied to the filling materials at a cross-head speed of 1 mm min-1 using a universal testing machine. The force that led to dislodgement of the filling was recorded in Newtons. The resistance to dislodgement was calculated in megapascals (MPa) by dividing the load in Newtons by the area of the bonded interface. The data were statistically analysed with two-way anova with Tukey's honestly significant difference (HSD) test. RESULTS: Biodentine had significantly higher resistance to dislodgement than DiaRoot BioAggregate (P < 0.001). The specimens with thinner remaining dentine had lower dislodgement resistance compared to those with dentine thicknesses of 1.50 and 2.25 mm (P < 0.001). The lowest mean value for dislodgement resistance was obtained from the DiaRoot BioAggregate group with 0.75 mm dentine thickness (2.72 ± 0.90 MPa). CONCLUSION: The dislodgement resistance of Biodentine and DiaRoot BioAggregate from root dentine was influenced by remaining dentine thickness, which determines dentinal tubular density.

Revision stapes surgery for lysis of the long process of the incus: comparing hydroxyapatite bone cement versus malleovestibulopexy and total ossicular replacement prosthesis.

The objective of the study was to report audiological results in revision stapes surgery, comparing hydroxyapatite (HAP) bone cement, malleovestibular (MV) prosthesis, and total ossicular replacement prosthesis (TORP). The study is a retrospective case review conducted in a tertiary referral center. Patients treated for revision stapes surgery from 2010 to 2014, where a lysis of the long process of the incus (LPI) was observed with the use of HAP bone cement, MV prosthesis, or a TORP were included in the study. The main outcomes measured were pre- and postoperative bone conduction (BC) and air conduction (AC) pure-tone averages (PTA) (0.5, 1, 2, 3 kHz), including high frequencies BC (HFBC) (1, 2, 3, 4 kHz) and air-bone gap (ABG). 107 revision stapes surgery were performed in 96 ears. Main cause of failure was LPI lysis in 38 cases (39.6 %). 31 patients were analyzed: HAP bone cement was used in 11 patients (Group I), MV prosthesis in ten patients (Group II), and TORP in ten patients (Group III). The mean post-operative ABG was 10.7 dB (±7.4) (p = 0.003), 10.7 dB (±8.8) (p = 0.001), and 16.9 dB (±9.8) (p = 0.001), respectively. There were no significant differences between groups. In Group I, the mean change in HFBC revealed an improvement of 5.6 dB (±7.9) (p = 0.03), while in Group III there was a significant deterioration of the thresholds of 5.8 dB (±7.6) (p = 0.04). There were no cases of post-operative anacusis. In revision stapes surgery when LPI is eroded, we recommend to perform a cement ossiculoplasty for stabilizing a standard Teflon piston when LPI is still usable, the LPI lengthening with cement being not recommended. When LPI is too eroded, we prefer performing a malleovestibulopexy, and reserve TORP for cases with a bad anatomical presentation.

Migration of alloplastic bone graft material in infected conditions: a case study and animal experiment.

PURPOSE: Distant migration associated with sinus lifting procedures has not been investigated. In the present study, a case of distant migration of graft material was observed, and the potential mechanisms of migration were analyzed using material analysis and in vivo experiments. MATERIALS AND METHODS: The migrated graft material was biphasic calcium phosphate-based alloplastic material (BCP), and its physical properties were compared with those of xenogenic material (Bio-Oss). The comparisons of the physical properties were performed using scanning electronic microscopic, x-ray diffraction, and Fourier-transform infrared absorbance spectra analysis. The comparative graft migration study was performed using the subcutaneous pocket model in rats (n = 10). The clinical case was analyzed by histologic section and energy dispersive x-ray (EDX) microanalysis. RESULTS: The observed diffraction patterns from the Bio-Oss revealed characteristic diffractions for the hydroxyapatite phase, and those from the BCP revealed additional diffractions that could be assigned to the tricalcium phosphate phase. In the animal model, the graft migration distances observed in the BCP group were significantly greater than those observed in the Bio-Oss group (P = .012). In the clinical case, the lymphatic vessels of the submandibular gland contained foreign materials that were morphologically similar to those of the maxillary sinus. EDX microanalysis revealed that the particles in the lymphatic vessels exhibited calcium concentrations that were approximately 200 times greater than those in the adjacent glandular tissue. CONCLUSIONS: In the present study, BCP-based sinus grafts had migrated into the submandibular glandular area by way of the lymphatic chain in the presented clinical case.

[Allergy of calcium phosphate cement material following skull reconstruction: a case report].

The paste form of calcium phosphate cement is often used in skull reconstruction because of the biocompatibility and early handling of these cements. Although it had rarely been shown to produce a foreign body reaction, we encountered a patient who experienced an allergic reaction to calcium phosphate cements(Biopex®. A patch test was performed and a positive reaction to magnesium phosphate was obtained. Biopex® contains magnesium phosphate, so we diagnosed this case as allergic reaction. Pathological analysis revealed infiltration of plasmacytes in the bone flap around the calcium phosphate cement. The postoperative course was uneventful 3 years after surgery. Allergy to calcium phosphate cements is rare, but must be considered in differential diagnosis of its side effects.

Radioactive synovectomy with (90) yttrium and (153) samarium hydroxyapatite in haemophilic joints: preliminary study on radiation safety.

Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153) Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3-51) received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5-10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.

Complications of hydroxyapatite bone cement use in cochlear implantation?

OBJECTIVE AND IMPORTANCE: To highlight the complications of using hydroxyapatite (HA) bone cement when implanting a cochlear implant (CI) device. CLINICAL PRESENTATION: A case series of three patients who had undergone cochlear implantation are presented. A bony defect was seen in the external auditory meatal wall posteriorly in all three cases. This was intimately related to the site of HA bone cement, which had been used to anchor the electrode array at the time of the original implantation. Persistent otorrhoea was usually a feature at clinical presentation. INTERVENTION (AND TECHNIQUE): Removal of the HA bone cement and repair of the bony defect has resulted in resolution of the otorrhoea and a functioning CI is present in all cases without further complications. CONCLUSION: The use of HA bone cement in cochlear implantation may cause dehiscence of the external auditory meatal wall. Our experience has shown that the electrode array does not need to be secured with cement. It is therefore recommended by this centre that HA cement should not be used to secure the electrode array in cochlear implantation surgery.

Inflammatory cell response to calcium phosphate biomaterial particles: an overview.

Bone is a metabolically active and highly organized tissue consisting of a mineral phase of hydroxyapatite (HA) and amorphous calcium phosphate (CaP) crystals deposited in an organic matrix. One objective of bone tissue engineering is to mimic the chemical and structural properties of this complex tissue. CaP ceramics, such as sintered HA and beta-tricalcium phosphate, are widely used as bone substitutes or prosthesis coatings because of their osteoconductive properties. These ceramic interactions with tissues induce a cell response that can be different according to the composition of the material. In this review, we discuss inflammatory cell responses to CaP materials to provide a comprehensive overview of mechanisms governing the integration or loosening of implants, which remains a major concern in tissue engineering. A focus on the effects of the functionalization of CaP biomaterials highlights potential ways to increase tissue integration and limit rejection processes.

Foreign body granuloma associated with dura-cranioplasty after resection of convexity meningioma with extracranial extension: case report.

A 72-year-old man presented with a space-occupying lesion at the site of the prior craniotomy one year after removal of a convexity meningioma with an extracranial extension. The lesion had grown outside the duraplasty with extracranial extension through the degenerative cranioplasty, and was removed. The histological diagnosis was granulation. The original dura-cranioplasty had been performed using Goretex dura substitute, hydroxyapatite cement, and fibrin glue-bonded autologous bone dust. This rare case of foreign body granuloma occurring after craniotomy with dura-cranioplasty indicates that detailed preoperative evaluation of tissue destruction based on neuroimaging is essential for construction of a suitable cranioplasty.

The effect of calcium phosphate nanoparticles on hormone production and apoptosis in human granulosa cells.

OBJECTIVES: Although many nanomaterials are being used in academia, industry and daily life, there is little understanding about the effects of nanoparticles on the reproductive health of vertebral animals, including human beings. An experimental study was therefore performed here to explore the effect of calcium phosphate nanoparticles on both steroid hormone production and apoptosis in human ovarian granulosa cells. METHODS: Calcium phosphate nanoparticles uptaking was evaluated by transmission electron microscopy (TEM). The cell cycle was assessed with propidium iodide-stained cells (distribution of cells in G0/G1, S, and G2/M phases) by flow cytometry. The pattern of cell death (necrosis and apoptosis) was analyzed by flow cytometry with annexin V-FITC/PI staining. The expression of mRNAs encoding P450scc, P450arom and StAR were determined by RT-PCR. Progesterone and estradiol levels were measured by radioimmunoassay. RESULTS: TEM results confirmed that calcium phosphate nanoparticles could enter into granulosa cells, and distributed in the membranate compartments, including lysosome and mitochondria and intracellular vesicles. The increased percentage of cells in S phase when cultured with nanoparticles indicated that there was an arrest at the checkpoint from phase S-to-G2/M (from 6.28 +/- 1.55% to 11.18 +/- 1.73%, p < 0.05). The increased ratio of S/(G2/M) implied the inhibition of DNA synthesis and/or impairment in the transition of the S progression stage. The apoptosis rate of normal granulosa cells was 7.83 +/- 2.67%, the apoptotic rate increased to 16.53 +/- 5.56% (P < 0.05) after the cells were treated with 100 microM calcium phosphate nanoparticles for 48 hours. Treatment with calcium phosphate nanoparticles at concentrations of 10-100 microM didn't significantly change either the progesterone or estradiol levels in culture fluid, and the expression levels of mRNAs encoding P450scc, P450arom and StAR after 48 h and 72 h period of treatment. CONCLUSION: Calcium phosphate nanoparticles interfered with cell cycle of cultured human ovarian granulosa cells thus increasing cell apoptosis. This pilot study suggested that effects of nanoparticles on ovarian function should be extensively investigated.

Sinus bone graft using new alloplastic bone graft material (Osteon)-II: clinical evaluation.

OBJECTIVES: The objective of this study was to clinically evaluate the use of Osteon as a sinus bone graft material and to measure the loss of sinus bone graft volume and marginal bone loss around the implants. STUDY DESIGN: Thirty-two implants were placed in 16 patients after maxillary sinus bone grafting. In 7 patients, maxillary sinus bone graft was performed first and 15 implants were placed after 4 months; in 9 patients, 17 implants were placed simultaneously with maxillary sinus bone grafting. Based on medical records and radiographs, intraoperative and postoperative complications were examined, and at 1 year after the placement of the upper fixture, the success rate of implants, peri-implant soft tissue condition, and the marginal bone loss were evaluated. Additionally, the sinus bone graft volume loss was evaluated by comparing the residual alveolar bone height of the preoperative maxillary sinus floor with that immediately after the operation and after 1 year. RESULTS: Regarding intraoperative complications, perforation of the maxillary sinus membrane occurred in 6 cases (37.5%), and after surgery maxillary sinusitis developed in 2 cases. During the healing period, 1 implant failed in osseointegration. At the last follow-up observation, none of cases showed marginal bone loss of >1 mm and a 96.9% success rate was seen. The follow-up observation period after placement of the superstructure was 12-30 months (average 15). Between the simultaneous placement group and the delayed placement group, marginal bone loss showed no statistically significant difference (P = .455). In the entire patient group, the volume of sinus bone graft loss did not correlate with marginal bone loss (P = .568). Preoperative alveolar bone height was 0.8-8.8 mm (mean 4.64), postoperative alveolar bone height was 12-21.8 mm (mean 17.67), and the alveolar bone height 1 year after the operation was 11.2-20.8 mm (mean 16.78). Between the group with perforation of the maxillary sinus membrane and the group without, no difference in marginal bone loss was observed (P = .628). Additionally, no difference in the volume of sinus bone graft resorption between the two groups was observed (P = .970). CONCLUSION: It was concluded that Osteon is suitable for use in sinus graft application.

Effectiveness of radiation synovectomy with samarium-153 particulate hydroxyapatite in rheumatoid arthritis patients with knee synovitis: a controlled randomized double-blind trial.

OBJECTIVES: The aim of the present study was to investigate the effectiveness of Samarium(153)-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid arthritis patients (60 knees) with chronic knee synovitis participated in a controlled double-blinded trial. Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group) or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium(153)-particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0) and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness, flexion, extension, knee circumference, Likert scale of improvement, percentage of improvement, SF-36 generic quality of life questionnaire, Stanford Health Assessment Questionnaire (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral corticosteroids, events and adverse effects, calls to the physician, and hospital visits. RESULTS: The sample was homogeneous at baseline, and there were no withdrawals. Improvement was observed in both groups in relation to T0, but no statistically significant differences between groups were observed regarding all variables at the time points studied. The Sm/TH group exhibited more adverse effects at T1 (p<0.05), but these were mild and transitory. No severe adverse effects were reported during follow-up. CONCLUSION: Intra-articular injection of Samarium(153)-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up.

Complications of hydroxyapatite bone cement reconstruction of retrosigmoid craniotomy: two cases.

Hydroxyapatite bone cement is a versatile material used to reconstruct many types of bony surgical defects, and its applications have been widely reported in the literature. Still, complications of its use do occur. We describe 2 cases of hydroxyapatite resorption and subsequent seroma formation in patients who had undergone retrosigmoid craniotomy. The presentation in both cases mimicked a CSF leak. In both cases, the fragmented cement was removed, and the patient experienced no further complications. While hydroxyapatite cement is a highly useful product for the reconstruction of some craniofacial or skull base defects, we believe that it should not be used for the reconstruction of retrosigmoid/suboccipital craniotomies because it is associated with unacceptably high complication rates. Surgeons must exercise caution in selecting candidates for hydroxyapatite reconstruction of cranial defects.