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Biomedical subjects

Shozo Takagi

Publications and source records attributed to Shozo Takagi.

18 recordsLinked to original sources

Effects of incorporating nanosized calcium phosphate particles on properties of whisker-reinforced dental composites.

Clinical data indicate that secondary caries and restoration fracture are the most common problems facing tooth restorations. Our ultimate goal was to develop mechanically-strong and caries-inhibiting dental composites. The specific goal of this pilot study was to understand the relationships between composite properties and the ratio of reinforcement filler/releasing filler. Nanoparticles of monocalcium phosphate monohydrate (MCPM) were synthesized and incorporated into a dental resin for the first time. Silicon carbide whiskers were fused with silica nanoparticles and mixed with the MCPM particles at MCPM/whisker mass ratios of 1:0, 2:1, 1:1, 1:2, and 0:1. The composites were immersed for 1-56 days to measure Ca and PO4 release. When the MCPM/whisker ratio was changed from 0:1 to 1:2, the composite flexural strength (mean +/- SD; n = 5) decreased from 174 +/- 26 MPa to 138 +/- 9 MPa (p < 0.05). A commercial nonreleasing composite had a strength of 112 +/- 14 MPa. When the MCPM/whisker ratio was changed from 1:2 to 1:1, the Ca concentration at 56 days increased from 0.77 +/- 0.04 mmol/L to 1.74 +/- 0.06 mmol/L (p < 0.05). The corresponding PO4 concentration increased from 3.88 +/- 0.21 mmol/L to 9.95 +/- 0.69 mmol/L (p < 0.05). Relationships were established between the amount of release and the MCPM volume fraction v(MCPM) in the resin: [Ca]= 42.9 v(MCPM) (2.7), and [PO4] = 48.7 v(MCPM) (1.4). In summary, the method of combining nanosized releasing fillers with reinforcing fillers yielded Ca- and PO4-releasing composites with mechanical properties matching or exceeding a commercial stress-bearing, nonreleasing composite. This method may be applicable to the use of other Ca-PO4 fillers in developing composites with high stress-bearing and caries-preventing capabilities, a combination not yet available in any dental materials.

Calcium Phosphates↗

Premixed calcium phosphate cements: synthesis, physical properties, and cell cytotoxicity.

OBJECTIVES: Calcium phosphate cement (CPC) is a promising material for dental, periodontal, and craniofacial repairs. However, its use requires on-site powder-liquid mixing that increases the surgical placement time and raises concerns of insufficient and inhomogeneous mixing. The objective of this study was to determine a formulation of premixed CPC (PCPC) with rapid setting, high strength, and good in vitro cell viability. METHODS: PCPCs were formulated from CPC powder+non-aqueous liquid+gelling agent+hardening accelerator. Five PCPCs were thus developed: PCPC-Tartaric, PCPC-Malonic, PCPC-Citric, PCPC-Glycolic, and PCPC-Malic. Formulations and controls were compared for setting time, diametral tensile strength, and osteoblast cell compatibility. RESULTS: Setting time (mean+/-S.D.; n=4) for PCPC-Tartaric was 8.2+/-0.8 min, significantly less than the 61.7+/-1.5 min for the Premixed Control developed previously (p<0.001). On 7th day immersion, the diametral tensile strength of PCPC-Tartaric reached 6.5+/-0.8 MPa, higher than 4.5+/-0.8 MPa of Premixed Control (p=0.036). Osteoblast cells displayed a polygonal morphology and attached to the nano-hydroxyapatite crystals in the PCPCs. All cements had similar live cell density values (p=0.126), indicating that the new PCPCs were as cell compatible as a non-premixed CPC control known to be biocompatible. Each of the new PCPCs had a cell viability that was not significantly different (p>0.1) from that of the non-premixed CPC control. SIGNIFICANCE: PCPCs will eliminate the powder-liquid mixing during surgery and may also improve the cement performance. The new PCPCs supported cell attachment and yielded a high cell density and viability. Their mechanical strengths approached the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. These nano-crystalline hydroxyapatite cements may be useful in dental, periodontal, and craniofacial repairs.

3T3 Cells↗

Fast setting calcium phosphate cement-chitosan composite: mechanical properties and dissolution rates.

Calcium phosphate cement (CPC) can self-harden in vivo to form hydroxyapatite (HA) with excellent osteoconductivity. In recent studies, CPC-chitosan composites are developed with high mechanical strength and washout resistance. The objectives of the present study are to optimize the setting time and mechanical properties of a CPC-chitosan composite by tailoring the chitosan content, and to evaluate the bioresorbability by using an in vitro dissolution model. Six chitosan mass fractions are tested: 0, 10, 15, 20, 25, and 30%. Specimens are immersed in solutions with pH ranging from 3.5 to 5 to simulate the acidic environments produced by osteoclasts in vivo. Dissolution is measured as the fraction of mass loss versus immersion time from 7d to 28d. The CPC-chitosan composite with 20% by mass chitosan has a setting time (mean+/-SD; n=4) of 13 1 min, significantly less than 87 7 min for CPC control without chitosan (p<0.05). The composite flexural strength (mean+/-SD; n 1/4 6) was 14 2 MPa, significantly higher than 4 1 MPa of CPC control (p<0.05). At an intermediate pH of 4.5, the fraction of mass loss for CPC with 20% chitosan and CPC control without chitosan are not significantly different (p>0.1). The dissolution rates (fraction of mass loss per day,%/d) were 1.05 for CPC control and 1.08 for CPC-chitosan. In summary, a CPC-chitosan composite is developed with fast-setting and a flexural strength three-fold of that of CPC control without chitosan. Both materials are soluble in acidic environments, indicating that adding chitosan did not compromise the bioresorbability of CPC. The strong and resorbable CPC-chitosan composite may be useful in moderate stress-bearing craniofacial and orthopedic repairs.

Bone Cements↗

Reduction in dentin permeability using a slurry containing dicalcium phosphate and calcium hydroxide.

Treatments that obdurate dentin tubules have been used for reducing dentin hypersensitivity. The purpose of this study was to determine the effect of a treatment with a slurry of micron sized calcium phosphate on the hydraulic conductance (L(p)) of etched dentin discs in vitro. The treatment slurry was prepared by mixing a powder mixture of dicalcium phosphate anhydrous and calcium hydroxide with a solution that contained sodium fluoride and carboxymethyl cellulose. The mean baseline L(p) (in mL cm(-2) s(-1) H(2)O cm(-1)) was 2.07 +/- 1.45 (mean +/- SD; n = 13)). After one treatment and 2, 4, and 7 days of incubation in a protein-free saliva-like solution (SLS), the mean relative L(p), presented as % of baseline, were 65 +/- 16, 42 +/- 27, 36 +/- 26, and 33 +/- 27 (n = 13), respectively. The L(p) values of the baseline and treatment after incubation in the SLS were significantly (p < 0.05) different. Scanning electron microscopic examination showed partial obturation of dentin tubules in the treated dentin. X-ray diffraction and chemical analyses indicated the major product formed from the slurry was a fluoride-containing hydroxyapatite. Treatment appeared effective in further reducing L(p) of dentin discs after incubation in the SLS.

Calcium Hydroxide↗

In-situ hardening hydroxyapatite-based scaffold for bone repair.

Musculoskeletal conditions are becoming a major health concern because of an aging population and sports- and traffic-related injuries. While sintered hydroxyapatite implants require machining, calcium phosphate cement (CPC) bone repair material is moldable, self-hardens in situ, and has excellent osteoconductivity. In the present work, new approaches for developing strong and macroporous scaffolds of CPC were tested. Relationships were determined between scaffold porosity and strength, elastic modulus and fracture toughness. A biocompatible and biodegradable polymer (chitosan) and a water-soluble porogen (mannitol) were incorporated into CPC: Chitosan to make the material stronger, fast-setting and anti-washout; and mannitol to create macropores. Flexural strength, elastic modulus, and fracture toughness were measured as functions of mannitol mass fraction in CPC from 0% to 75%. After mannitol dissolution in a physiological solution, macropores were formed in CPC in the shapes of the original entrapped mannitol crystals, with diameters of 50 microm to 200 microm for cell infiltration and bone ingrowth. The resulting porosity in CPC ranged from 34.4% to 83.3% volume fraction. At 70.2% porosity, the hydroxyapatite scaffold possessed flexural strength (mean +/- sd; n = 6) of (2.5 +/- 0.2) MPa and elastic modulus of (0.71 +/- 0.10) GPa. These values were within the range for sintered porous hydroxyapatite and cancellous bone. Predictive equations were established by regression power-law fitting to the measured data (R(2) > 0.98) that described the relationships between scaffold porosity and strength, elastic modulus and fracture toughness. In conclusion, a new graft composition was developed that could be delivered during surgery in the form of a paste to harden in situ in the bone site to form macroporous hydroxyapatite. Compared to conventional CPC without macropores, the increased macroporosity of the new apatite scaffold may help facilitate implant fixation and tissue ingrowth.

Aging↗

Development of a nonrigid, durable calcium phosphate cement for use in periodontal bone repair.

BACKGROUND: Calcium phosphate cement (CPC) hardens in situ to form hydroxyapatite and has been used in dental and craniofacial restorative applications. However, when CPC was used in periodontal osseous repair, tooth mobility resulted in the fracture and exfoliation of the brittle CPC implant. The objective of the authors' study was to develop a strong and nonrigid CPC to provide compliance for tooth mobility without fracturing the implant. METHODS: The authors used tetracalcium phosphate, dicalcium phosphate anhydrous and biopolymer chitosan to develop a strong and nonrigid CPC. They used a powder:liquid ratio of 2:1, compared with the 1:1 ratio of a previously developed nonrigid CPC control. Specimens were characterized using a flexural test, scanning electron microscopy and powder X-ray diffraction. RESULTS: After 28 days of immersion, the new cement had a flexural strength (mean +/- standard deviation; n = 6) of 5.2 +/- 1.0 megapascals, higher than 1.8 +/- 1.5 MPa for the control (P < .05) and overlapping the reported strengths of sintered hydroxyapatite implants and cancellous bone. This cement showed a high ductility with a strain at peak load of 6.5 +/- 1.3 percent, compared with 4.4 +/- 1.9 percent for the control; both were 20-fold higher than the 0.2 percent of the conventional CPC. Nanosized hydroxyapatite crystals, similar to those in teeth and bones, were formed in the cements. CONCLUSIONS: The new nonrigid cement, containing nanohydroxyapatite crystals, possessed a high ductility and superior fracture resistance. This strong, tough and nonrigid CPC may be useful in periodontal repair to provide compliance for tooth mobility without fracture. CLINICAL IMPLICATIONS: The results of this study may yield the first self-hardening and nonrigid hydroxyapatite composite with high strength and durability and large deformation capability to be useful in the regeneration of periodontal osseous defects.

Alveolar Bone Loss↗

High early strength calcium phosphate bone cement: effects of dicalcium phosphate dihydrate and absorbable fibers.

Calcium phosphate cement (CPC) sets in situ to form resorbable hydroxyapatite with chemical and crystallographic similarity to the apatite in human bones, hence it is highly promising for clinical applications. The objective of the present study was to develop a CPC that is fast setting and has high strength in the early stages of implantation. Two approaches were combined to impart high early strength to the cement: the use of dicalcium phosphate dihydrate with a high solubility (which formed the cement CPC(D)) instead of anhydrous dicalcium phosphate (which formed the conventional cement CPC(A)), and the incorporation of absorbable fibers. A 2 x 8 design was tested with two materials (CPC(A) and CPC(D)) and eight levels of cement reaction time: 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 8 h, and 24 h. An absorbable suture fiber was incorporated into cements at 25% volume fraction. The Gilmore needle method measured a hardening time of 15.8 min for CPC(D), five-fold faster than 81.5 min for CPC(A), at a powder:liquid ratio of 3:1. Scanning electron microscopy revealed the formation of nanosized rod-like hydroxyapatite crystals and platelet crystals in the cements. At 30 min, the flexural strength (mean +/- standard deviation; n = 5) was 0 MPa for CPC(A) (the paste did not set), (4.2 +/- 0.3) MPa for CPC(D), and (10.7 +/- 2.4) MPa for CPC(D)-fiber specimens, significantly different from each other (Tukey's at 0.95). The work of fracture (toughness) was increased by two orders of magnitude for the CPC(D)-fiber cement. The high early strength matched the reported strength for cancellous bone and sintered porous hydroxyapatite implants. The composite strength S(c) was correlated to the matrix strength S(m): S(c) = 2.16S(m). In summary, substantial early strength was imparted to a moldable, self-hardening and resorbable hydroxyapatite via two synergistic approaches: dicalcium phosphate dihydrate, and absorbable fibers. The new fast-setting and strong cement may help prevent catastrophic fracture or disintegration in moderate stress-bearing bone repairs.

Bone Substitutes↗

Hydrolysis of tetracalcium phosphate under a near-constant-composition condition--effects of pH and particle size.

Tetracalcium phosphate (TTCP) is a component of a number of calcium phosphate cements used clinically for bone defect repairs. The strength, phase composition, and solubility of the set cement are highly dependent on the reactions of the cement components during setting. This study investigated hydrolysis reactions of TTCP under solution compositions chosen to mimic the compositions of the cement liquid during setting. The study utilized a pseudo-constant-composition technique that allowed both the rate and stoichiometry of the reaction to be determined while the reaction proceeded under a specific, constantly held solution pH, thereby keeping a constant calcium-to-phosphate ratio in solution. The hydrolysis experiments were conducted using either a fine (median particle size 3.5 microm) or coarse (median particle size 13.2 microm) TTCP powder at pH 7, 8 and 10. Low crystalline calcium (Ca)-deficient hydroxyapatite (HA) was the product in all experiments. Both the solution pH and TTCP particle size produced significant effects on all aspects of the hydrolysis reaction. At a given pH, the fine TTCP produced a HA product with a greater Ca deficiency than did the coarse TTCP. For a given particle size, the Ca deficiency generally decreased with increasing pH. Hydrolysis reaction rate generally decreased with increasing pH or TTCP particle size. At pH 7 and 8, the solution was undersaturated with respect to TTCP and supersaturated with respect to HA, suggesting that the reaction rate was limited by TTCP dissolution. In contrast, at pH 10, the solution was approximately saturated with respect to TTCP and highly supersaturated with respect to HA, suggesting that HA formation was the rate-determining step of the reaction. The findings provided useful insights into the setting reaction mechanisms of TTCP-containing calcium phosphate cements.

Biocompatible Materials↗

Premixed rapid-setting calcium phosphate composites for bone repair.

Although calcium phosphate cement (CPC) is promising for bone repair, its clinical use requires on site powder-liquid mixing. To shorten surgical time and improve graft properties, it is desirable to develop premixed CPC in which the paste remains stable during storage and hardens only after placement into the defect. The objective of this study was to develop premixed CPC with rapid setting when immersed in a physiological solution. Premixed CPCs were formulated using the following approach: Premixed CPC = CPC powder + nonaqueous liquid + gelling agent + hardening accelerator. Three premixed CPCs were developed: CPC-monocalcium phosphate monohydrate (MCPM), CPC-chitosan, and CPC-tartaric. Setting time for these new premixed CPCs ranged from 5.3 to 7.9 min, significantly faster than 61.7 min for a premixed control CPC reported previously (p < 0.05). SEM revealed the formation of nano-sized needle-like hydroxyapatite crystals after 1 d immersion and crystal growth after 7 d. Diametral tensile strength for premixed CPCs at 7 d ranged from 2.8 to 6.4 MPa, comparable to reported strengths for cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells attained a normal polygonal morphology on CPC-MCPM and CPC-chitosan with cytoplasmic extensions adhering to the nano-hydroxyapatite crystals. In summary, fast-setting premixed CPCs were developed to avoid the powder-liquid mixing in surgery. The pastes hardened rapidly once immersed in physiological solution and formed hydroxyapatite. The cements had strengths matching those of cancellous bone and sintered porous hydroxyapatite and non-cytotoxicity similar to conventional non-premixed CPC.

3T3 Cells↗

Fast-setting calcium phosphate scaffolds with tailored macropore formation rates for bone regeneration.

Calcium phosphate cement (CPC) is highly promising for craniofacial and orthopedic repair because of its ability to self-harden in situ to form hydroxyapatite with excellent osteoconductivity. However, its low strength, long hardening time, and lack of macroporosity limit its use. This study aimed to develop fast-setting and antiwashout CPC scaffolds with high strength and tailored macropore formation rates. Chitosan, sodium phosphate, and hydroxypropyl methylcellulose (HPMC) were used to render CPC fast-setting and resistant to washout. Absorbable fibers and mannitol porogen were incorporated into CPC for strength and macropores for bone ingrowth. Flexural strength, work-of-fracture, and elastic modulus were measured vs. immersion time in a physiological solution. Hardening time (mean +/- SD; n = 6) was 69.5 +/- 2.1 min for CPC-control, 9.3 +/- 2.8 min for CPC-HPMC-mannitol, 8.2 +/- 1.5 min for CPC-chitosan-mannitol, and 6.7 +/- 1.6 min for CPC-chitosan-mannitol-fiber. The latter three compositions were resistant to washout, whereas the CPC-control paste showed washout in a physiological solution. Immersion for 1 day dissolved mannitol and created macropores in CPC. CPC-chitosan-mannitol-fiber scaffold had a strength of 4.6 +/- 1.4 MPa, significantly higher than 1.2 +/- 0.1 MPa of CPC-chitosan-mannitol scaffold and 0.3 +/- 0.2 MPa of CPC-HPMC-mannitol scaffold (Tukey's). The strength of CPC-chitosan-mannitol-fiber scaffold was maintained up to 42 days and then decreased because of fiber degradation. Work-of-fracture and elastic modulus showed similar trends. Long cylindrical macropore channels were formed in CPC after fiber dissolution. The resorbable, fast-setting, anti-washout and strong CPC scaffold should be useful in craniofacial and orthopedic repairs. The novel method of combining fast- and slow-dissolution porogens/fibers to produce scaffolds with high strength and tailored macropore formation rates to match bone healing rates may have wide applicability to other biomaterials.

Bone Regeneration↗

Synergistic reinforcement of in situ hardening calcium phosphate composite scaffold for bone tissue engineering.

Calcium phosphate cement (CPC) hardens in situ to form solid hydroxyapatite, can conform to complex cavity shapes without machining, has excellent osteoconductivity, and is able to be resorbed and replaced by new bone. Therefore, CPC is promising for use in craniofacial and orthopaedic repairs. However, the low strength and lack of macroporosity of CPC limit its use. The aim of the present study was to increase the strength and toughness of CPC while creating macropores suitable for cell infiltration and bone ingrowth, and to investigate the effects of chitosan and mesh reinforcement on the composite properties. Specimens were self-hardened in 3 mm x 4 mm x 25 mm molds, immersed in a physiological solution for 1-84 d, and tested in three-point flexure. After 1d, the unreinforced CPC control had a flexural strength (mean+/-s.d.; n=6) of (3.3+/-0.4)MPa. The incorporation of chitosan or mesh into CPC increased the strength to (11.9+/-0.8) and (21.3+/-2.7)MPa, respectively. The incorporation of both chitosan and mesh synergistically into CPC dramatically increased the strength to (43.2+/-4.1)MPa. The work-of-fracture (WOF) (toughness) was also increased by two orders of magnitude. After 84 d immersion in a simulated physiological solution, the meshes in CPC dissolved and formed interconnected cylindrical macropores. The novel CPC scaffold had a flexural strength 39% higher, and WOF 256% higher than the conventional CPC without macropores. The new composite had an elastic modulus within the range for cortical bone and cancellous bone, and a flexural strength higher than those for cancellous bone and sintered porous hydroxyapatite implants. In conclusion, combining two different reinforcing agents together in self-hardening CPC resulted in superior synergistic strengthening compared to the traditional use of a single reinforcing agent. The strong and macroprous CPC scaffold may be useful in stress-bearing craniofacial and orthopaedic repairs.

Body Fluids↗

Histopathological and cell enzyme studies of calcium phosphate cements.

New types of self-setting calcium phosphate cement (N-CPC), which do not contain tetracalcium phosphate, were recently developed. N-CPCs harden in 10 minutes with phosphate solution as the cement liquid, and form hydroxyapatite as the set product. The objectives of the present study were to evaluate the biocompatibility (Study I) and cell enzyme activity of N-CPCs and a conventional CPC (Study II). Four experimental cements were tested: (1) dicalcium phosphate anhydrous (DCPA) and calcium oxide; (2) DCPA and calcium hydroxide; (3) tricalcium phosphate and calcium carbonate; and (4) DCPA and tetracalcium phosphate. Phosphate solution was used as the cement liquid for cements (1)-(3), and water for cement (4). Sintered hydroxyapatite particles (5) were used as a control. The test materials were implanted subcutaneously in rats. Four weeks after operation, the animals were sacrificed and histopathological observations were performed. Cements (2) and (3) showed no inflammatory reaction, and were surrounded only by very thin fibrous connective tissues. The histopathological reactions of N-CPCs were nearly identical and were similar to (4) and (5). In addition, effects of alkaline phosphatase (ALP-ase) activity--invoked by the presence of cements (3) and (4)--on osteoblast-like cells derived from dog alveolar bone were also examined because ALP-ase activity is closely related to new bone formation. These results indicated that (3) and (4) were highly compatible with subcutaneous tissues and suggested that these cements may enhance new bone formation.

Acid Phosphatase↗

Premixed calcium-phosphate cement pastes.

A self-hardening calcium-phosphate cement (CPC) containing Ca(4)(PO(4))(2)O and CaHPO(4) has been shown in clinical studies to be efficacious for repairing bone defects. This and several other similar CPCs harden in 10 min with the use of a phosphate solution as the liquid and form hydroxyapatite (HA) as the product. The present study investigated the properties of water-free, glycerol-containing CPC pastes that are stable in the package and would harden only after being delivered to a defect site where glycerol-tissue fluids exchange occurs. Premixed CPC pastes were prepared by combining cement liquids containing glycerol and various amounts of hydroxypropyl methylcellulose/Na(2)HPO(4), with CPC powders that contained (1) Ca(4)(PO(4))(2)O and CaHPO(4), (2) alpha-Ca(3)(PO(4))(2) and CaCO(3), or (3) CaHPO(4) and Ca(OH)(2). The hardening times and 1-d and 7-d diametral tensile strengths were measured on samples that hardened in an in vitro model that allowed exchange of glycerol and physiologic-like solution (PLS) through fritted glass slides at 37 degrees C. All pastes had excellent washout resistance; they remained intact and hardened while immersed in PLS and formed HA as products. Newman-Keuls multiple comparison tests indicated that the Na(2)HPO(4) amount, not the hydroxypropyl methylcellulose (HMC) amount, significantly (p < 0.05) affected the strength and hardening time. Although the premixed CPCs generally have longer hardening times and lower strengths, these pastes have excellent washout resistance before hardening and can be prepared in advance under well-controlled conditions.

Body Fluids↗

A dual constant-composition titration system as an in vitro resorption model for comparing dissolution rates of calcium phosphate biomaterials.

It has been postulated that the in vivo resorption rates of calcium-phosphate bone-graft materials are closely related to their dissolution rates in demineralizing solutions having ionic compositions mimicking the acidic environment produced by osteoclasts. Thus, it should be possible to use an in vitro model to produce dissolution-rate data of calcium-phosphate materials as a starting point for predicting in vivo resorption properties. Direct pH measurements of the extracellular fluid from bone-resorbing cells showed that the pH was as low as 3. In the present study, a dual constant-composition dissolution system was used as an in vitro resorption model to compare dissolution rates of different calcium-phosphate materials. NIST standard reference hydroxyapatite (HA), dicalcium-phosphate dihydrate (DCPD), and calcium-phosphate cement (CPC) discs of known dimensions (6-mm d x 3-mm h) were allowed to dissolve at 37 degrees C in a solution that had an inorganic composition similar to that of serum ([Ca] = 1.15 mmol/l; [P] = 1.2 mmol/l; [KCl] = 133 mmol/l) and a pH of 3.0. A Ca ion-specific electrode and a pH electrode were used to control the addition of titrants to compensate for the increases in calcium and phosphate concentrations, respectively, in the demineralizing solution. The rate and stoichiometry (Ca/P molar ratio) of dissolution were obtained from the titration data. Each solid dissolved at an approximately constant rate during the dissolution process. The dissolution rates, expressed in mg cm(-2) min(-1), (mean +/- standard deviation, n = 5) were for HA: 6.58 +/- 1.22; DCPD: 21.0 +/- 2.6; and CPC: 8.21 +/- 0.73. DCPD dissolved three times faster than HA (p < 0.05). CPC dissolved 1.2 times faster than HA but the difference was not statistically significant (p > 0.05). This model can be used to study the rate and stoichiometry of dissolution of calcium-phosphate bone-graft materials and coatings under a wide range of mineral saturation conditions.

Absorbable Implants↗

Mechanical properties and biochemical activity of remineralizing resin-based Ca-PO4 cements.

OBJECTIVE: This study examined strength and bioactive (remineralizing) properties of a powder/liquid formulation (Cement I) and a more practical two-paste formulation (Cement II) of a fluoride-releasing resin-based Ca-PO(4) cement. METHODS: For the remineralization potential, the dissolution of calcium, total ionic phosphate and fluoride from set cement specimens were determined in buffered saline and saliva-like solution (SLS). Artificial caries lesions were produced on coronal dentin of extracted human molars. On each tooth, two defined areas were coated, one with a composite resin (calcium-free control), the other with either Cement I or II. After incubation in SLS, the mineral loss under the cement was analyzed by digitized microradiography and compared to that under the control. RESULTS: The diametral tensile strength of Cement II of approximately 30 MPa after 24 h and 23 MPa after 4 weeks was 2 to 3 times higher than that of Cement I (ANOVA, t-test, p<0.05). Calculations of the ion-activity products and Gibb's free energy from solution ion concentrations indicated a significant potential for the formation of fluor- and/or hydroxyapatite. Concurrently, both cements caused increases of 47% (Cement I) and 38% (Cement II) in the lesion mineral content over that underneath the corresponding controls. SIGNIFICANCE: These in vitro results suggest that the stronger Cement II could serve as a restoration-supporting lining material and could remineralize dentin in areas where complete removal of carious tissue is contra-indicated.

Apatites↗

Properties of elastomeric calcium phosphate cement-chitosan composites.

OBJECTIVE: Self-hardening calcium phosphate cements (CPC) have been shown to be efficacious in a number of clinical applications. For some applications it is desirable to have CPC in a non-rigid resorbable elastomeric matrix. In the present study, chitosan was evaluated as the matrix for preparing CPC-chitosan composites. METHODS: Cement specimens were prepared by mixing CPC powder (an equimolar mixture of tetracalcium phosphate and dicalcium phosphate anhydrous) with a chitosan solution at a powder/liquid ratio of 2-2.5. The setting time was measured by a Gilmore needle method. A standard three-point flexural test was used to fracture the specimens at a crosshead speed of 0.5 mm/min. Powder X-ray diffraction analysis was used to determine the conversion of the CPC to hydroxyapatite. RESULTS: The CPC-chitosan composites were more stable in water than conventional CPC. They did not disintegrate even when placed in water immediately after mixing. The CPC-chitosan paste hardened within 10 min in all cases. The 1d mean flexural modulus (GPa) for the control CPC was 5.3 (0.3) (mean (standard deviation); n=5), and that for CPC-chitosan composites were between 2.7 (0.3) and 4.7 (0.3). The 1d mean flexural strength (MPa) for the control was 16.6 (1.9), and that for the CPC-chitosan ranged from 4.5 (0.5) and 12.0 (1.0) (n=5). Chitosan did not interfere the conversion of CPC components to hydroxyapatite. SIGNIFICANCE: This study demonstrates that CPC-chitosan composites are stable in a wet environment and have acceptable mechanical strengths for clinical applications.

Biocompatible Materials↗

Histopathologic reaction of a calcium phosphate cement for alveolar ridge augmentation.

The objective of the present study was to evaluate the feasibility of using a calcium phosphate cement (CPC) in the reconstruction of a defective alveolar ridge in conjunction with implant placement. The CPC consisted of an equimolar amount of tetracalcium phosphate and dicalcium phosphate anhydrous. At the beginning of the experiment, all mandibular premolar teeth of mature beagle dogs were extracted. After 1 month of healing, alveolar bone was reduced to make a space for a CPC block that was prefabricated from a CPC mixed with water at a powder/liquid ratio of 5 g/mL. After an additional month, 8-mm long hydroxyapatite-coated titanium implants were placed in such a way that the apical half was embedded into alveolar bone and the coronal half in the preformed CPC block. The dogs were sacrificed and biopsies were obtained at 1, 3, and 6 months after surgery. Sections that included implants were evaluated for integration of the CPC block to the alveolar bone and of the implant to the alveolar bone. Additional sections without the implants served as controls. The results obtained from this study show that the CPC ridge augmentation gradually is replaced by natural bone. Six months after surgery, histopathologic features of the augmentation area were quite similar to those of natural alveolar bone. The coronal half of the implants, previously surrounded by the CPC block, was firmly fixed by natural bone. Therefore, this method may be useful for increasing the height of the alveolar ridge.

Alveolar Process↗

Fluorescent labeling analysis and electron probe microanalysis for alveolar ridge augmentation using calcium phosphate cement.

Our previous histopathological study showed that the augmentation block, prepared from a calcium phosphate cement (CPC) mixed with H2O at powder to liquid ratio of 5 g/mL, placed on the alveolar bone ridge, was gradually replaced by natural bone. In the present study, fluorescent labeling analysis (FLA) and electron probe microanalysis (EPMA) were performed on the same surgical site of the above histopathological study. Fluorescent labeling agents, that would be incorporated into newly formed mineralized tissues, were injected into dogs intramuscularly twice a week during the 3 week period that ended 1 week before sacrifice. The specimens obtained from the block were subjected to FLA for assessing the extent of new bone formation and to EPMA for measuring the elemental (Ca, P, Mg) distributions. FLA results showed the presence of newly formed bone at 1 month after surgery. EPMA results showed that the elemental distributions in the augmentation site were similar to those of the residual bone area at 6 months after surgery. FLA and EPMA examinations also indicated that the implants were surrounded and fixed by natural bone chronologically. A CPC augmentation block is clearly useful for alveolar ridge augmentation and osteointegrated implant fixation.

Alveolar Process↗