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Biomedical subjects

Hockin H K Xu

Publications and source records attributed to Hockin H K Xu.

At least 19 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↗

Strong calcium phosphate cement-chitosan-mesh construct containing cell-encapsulating hydrogel beads for bone tissue engineering.

Calcium phosphate cement (CPC) can conform to complex cavity shapes and set in situ to form bioresorbable hydroxyapatite. The aim of this study was to introduce cell-encapsulating alginate hydrogel beads into CPC and to improve the mechanical properties using chitosan and fiber mesh reinforcement. Because the CPC setting was harmful to the MC3T3-E1 osteoblast cells, alginate was used to encapsulate and protect the cells in CPC. Cells were encapsulated into alginate beads, which were then mixed into three pastes: conventional CPC, CPC-chitosan, and CPC-chitosan-mesh. After 1 day culture inside the setting cements, there were numerous live cells and very few dead cells, indicating that the alginate beads adequately protected the cells. Cell viability was assessed by measuring the mitochondrial dehydrogenase activity, using a Wst-1 colorimetric assay. Absorbance at 450 nm (arbitrary units) (mean +/- SD; n = 5) was 1.36 +/- 0.41 for cells inside conventional CPC, 1.29 +/- 0.24 for cells inside CPC-chitosan composite, and 0.73 +/- 0.22 for cells inside CPC-chitosan-mesh composite. All three values were similar to 1.00 +/- 0.14 for the control with cells in beads in the cell culture medium without any CPC (Tukey's at p = 0.05). Flexural strength for conventional CPC containing cell-encapsulating beads was 1.3 MPa. It increased to 2.3 MPa when chitosan was incorporated. It further increased to 4.3 MPa with chitosan and the reinforcement from one fiber mesh, and 9.5 MPa with chitosan and three sheets of fiber mesh. The latter two strengths matched reported strengths for sintered porous hydroxyapatite implants and cancellous bone. In summary, cell-encapsulated-alginate-CPC constructs showed favorable cell viability. The use of chitosan and mesh progressively improved the mechanical properties. These strong, in situ hardening, and cell-seeded hydroxyapatite cements may have potential for bone tissue engineering in moderate stress-bearing applications.

Alginates↗

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↗

Injectable and macroporous calcium phosphate cement scaffold.

Calcium phosphate cement (CPC) can be molded and self-hardens in vivo to form resorbable hydroxyapatite with excellent osteoconductivity. The objective of this study was to develop an injectable, macroporous and strong CPC, and to investigate the effects of porogen and absorbable fibers. Water-soluble mannitol was used as porogen and mixed with CPC at mass fractions from 0% to 50%. CPC with 0-40% mannitol was fully extruded under a syringe force of 10 N. The paste with 50% mannitol required a 100-N force which extruded only 66% of the paste. At fiber volume fraction of 0-5%, the paste was completely extruded. However, at 6% and 7.5% fibers, some fibers were left in the syringe after the paste was extruded. The injectable CPC scaffold had a flexural strength (mean+/-sd; n=5) of (3.2+/-1.0) MPa, which approached the reported strengths for sintered porous hydroxyapatite implants and cancellous bone. In summary, the injectability of a ceramic scaffold, a macroporous CPC, was studies for the first time. Processing parameters were tailored to achieve high injectability, macroporosity, and strength. The injectable and strong CPC scaffold may be useful in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques.

Biomechanical Phenomena↗

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↗

Injectable and rapid-setting calcium phosphate bone cement with dicalcium phosphate dihydrate.

Calcium phosphate cement (CPC) sets in situ with intimate adaptation to the contours of defect surfaces, and forms an implant having a structure and composition similar to hydroxyapatite, the putative mineral in teeth and bones. The objective of the present study was to develop an injectable CPC using dicalcium phosphate dihydrate (DCPD) with a high solubility for rapid setting. Two agents were incorporated to impart injectability and fast-hardening to the cement: a hardening accelerator (sodium phosphate) and a gelling agent (hydroxypropyl methylcellulose, HPMC). The cement with DCPD was designated as CPC(D), and the conventional cement was referred to as CPC(A). Using water without sodium phosphate, CPC(A) had a setting time of 82 +/- 6 min. In contrast, CPC(D) exhibited rapid setting with a time of 17 +/- 1 min. At 0.2 mol/L sodium phosphate, setting time for CPC(D) was 15 +/- 1 min, significantly faster than 40 +/- 2 min for CPC(A) (Tukey's at 0.95). Sodium phosphate decreased the paste injectability (measured as the paste mass extruded from the syringe divided by the original paste mass inside the syringe). However, the addition of HPMC dramatically increased the paste injectability. For CPC(D), the injectability was increased from 65% +/- 12% without HPMC to 98% +/- 1% with 1% HPMC. Injectability of CPC(A) was also doubled to 99% +/- 1%. The injectable and rapid-setting CPC(D) possessed flexural strength and elastic modulus values overlapping the reported values for sintered porous hydroxyapatite implants and cancellous bone. In summary, the rapid setting and relatively high strength and elastic modulus of CPC(D) should help the graft to quickly attain strength and geometrical integrity within a short period of time postoperatively. Furthermore, the injectability of CPC(D) may have potential for procedures involving defects with limited accessibility or narrow cavities, when there is a need for precise placement of the paste, and when using minimally invasive surgical techniques.

Biocompatible Materials↗

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↗

Effects of synergistic reinforcement and absorbable fiber strength on hydroxyapatite bone cement.

Approximately a million bone grafts are performed each year in the United States, and this number is expected to increase rapidly as the population ages. Calcium phosphate cement (CPC) can intimately adapt to the bone cavity and harden to form resorbable hydroxyapatite with excellent osteoconductivity and bone-replacement capability. The objective of this study was to develop a strong CPC using synergistic reinforcement via suture fibers and chitosan, and to determine the fiber strength-CPC composite strength relationship. Biopolymer chitosan and cut suture filaments were randomly mixed into CPC. Both suture filaments and composite were immersed in a physiological solution. After 1-day immersion, cement flexural strengths (mean +/- SD; n = 6) were: (2.7 +/- 0.8) MPa for CPC control; (11.2 +/- 1.0) MPa for CPC-chitosan; (17.7 +/- 4.4) MPa for CPC-fiber composite; and (40.5 +/- 5.8) MPa for CPC-chitosan-fiber composite. They are significantly different from each other (Tukey's at 0.95). The strength increase from chitosan and fiber together in CPC was much more than that from either fiber or chitosan alone. The composite strength became (9.8 +/- 0.6) MPa at 35-day immersion and (4.2 +/- 0.7) MPa at 119 days, comparable to reported strengths for sintered porous hydroxyapatite implants and cancellous bone. After suture fiber dissolution, long macropore channels were formed in CPC suitable for cell migration and tissue ingrowth. A semiempirical relationship between suture fiber strength S(F) and composite strength S(C) were obtained: S(C) = 14.1 + 0.047 S(F), with R = 0.92. In summary, this study achieved substantial synergistic effects by combining random suture filaments and chitosan in CPC. This may help extend the use of the moldable, in situ hardening hydroxyapatite to moderate stress-bearing orthopedic applications. The long macropore channels in CPC should be advantageous for cell infiltration and bone ingrowth than conventional random pores and spherical pores.

Bone Substitutes↗

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↗

Fast setting calcium phosphate-chitosan scaffold: mechanical properties and biocompatibility.

Calcium phosphate cement (CPC) sets in situ to form hydroxyapatite and is highly promising for a wide range of clinical applications. However, its low strength limits its use to only non-stress applications, and its lack of macroporosity hinders cell infiltration, bone ingrowth and implant fixation. The aim of this study was to develop strong and macroporous CPC scaffolds by incorporating chitosan and water-soluble mannitol, and to examine the biocompatibility of the new graft with an osteoblast cell line and an enzymatic assay. Two-way ANOVA identified significant effects on mechanical properties from chitosan reinforcement and powder:liquid ratio (p<0.001). The flexural strength of CPC-chitosan composite at a powder:liquid ratio of 2 was (13.6+/-1.2) MPa, which was significantly higher than (3.2+/-0.6) MPa for CPC control without chitosan (Tukey's at 0.95). At a powder:liquid ratio of 3.5, CPC-chitosan had a strength of (25.3+/-2.9) MPa, which was significantly higher than (10.4+/-1.7) MPa for CPC control. The scaffolds possessed total pore volume fractions ranging from 42.0% to 80.0%, and macroporosity up to 65.5%. At total porosities of 52.2-75.2%, the scaffold had strength and elastic modulus values similar to those of sintered porous hydroxyapatite and cancellous bone. Osteoblast mouse cells (MC3T3-E1) were able to adhere, spread and proliferate on CPC-chitosan specimens. The cells, which ranged from about 20 to 50 microm including the cytoplasmic extensions, infiltrated into the 165-271 microm macropores of the scaffold. In summary, substantial reinforcement and macroporosity were imparted to a moldable, fast-setting, biocompatible, and resorbable hydroxyapatite graft. The highly porous scaffold may facilitate bone ingrowth and implant fixation in vivo. In addition, the two to three times increase in strength may help extend the use of CPC to larger repairs in moderately stress-bearing locations.

Absorbable Implants↗

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↗

Self-hardening calcium phosphate cement-mesh composite: reinforcement, macropores, and cell response.

Calcium phosphate cement (CPC) self-hardens to form hydroxyapatite, has excellent osteoconductivity and bone-replacement ability, and is promising for craniofacial and orthopedic repair. However, its low strength limits CPC to only nonstress repairs. This study aimed to reinforce CPC with meshes to increase strength, and to form macropores in CPC for bone ingrowth after mesh dissolution. A related aim was to evaluate the biocompatibility of the new CPC-mesh composite. Absorbable polyglactin meshes, a copolymer of poly(glycolic) and poly(lactic) acids, were incorporated into CPC to provide strength and then form interconnected cylindrical macropores suitable for vascular ingrowth. The composite flexural strength, work-of-fracture, and elastic modulus were measured as a function of the number of mesh sheets in CPC ranging from 1 (a mesh on the tensile side of the specimen) up to 13 (mesh sheets throughout the entire specimen), and as a function of immersion time in a physiological solution from 1 to 84 days. Cell culture was performed with osteoblast-like cells and the cell viability was quantified using an enzymatic assay. The strengths (mean +/- SD; n = 6) of CPC containing 13 or 6 meshes were 24.5 +/- 7.8 and 19.7 +/- 4.3 MPa, respectively, not significantly different from each other; both were significantly higher than 8.8 +/- 1.9 MPa of CPC without mesh (Tukey's at 0.95). The work-of-fracture of CPC with 13 or 6 meshes was 3.35 +/- 0.80 and 2.95 +/- 0.58 kJ/m(2), respectively, two orders of magnitude higher than 0.021 +/- 0.006 kJ/m(2) of CPC without mesh. Interconnected macropores were formed in CPC at 84 days' immersion. The new CPC-mesh formulation supported the adhesion, spreading, proliferation, and viability of osteoblast-like cells in vitro. In conclusion, absorbable meshes in CPC increased the implant strength by three-fold and work-of-fracture by 150 times; interconnected macropores suitable for bone ingrowth were created in CPC after mesh dissolution. The higher strength may help extend the use of CPC to larger stress-bearing repairs, and the macropores may facilitate tissue ingrowth and integration of CPC with adjacent bone.

Biocompatible Materials↗

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↗

Strong and bioactive composites containing nano-silica-fused whiskers for bone repair.

Self-hardening calcium phosphate cement (CPC) sets to form hydroxyapatite with high osteoconductivity, but its brittleness and low strength limit its use to only non-stress bearing locations. Previous studies developed bioactive composites containing hydroxyapatite fillers in Bis-GMA-based composites for bone repair applications, and they possessed higher strength values. However, these strengths were still lower than the strength of cortical bone. The aim of this study was to develop strong and bioactive composites by combining CPC fillers with nano-silica-fused whiskers in a resin matrix, and to characterize the mechanical properties and cell response. Silica particles were fused to silicon carbide whiskers to roughen the whisker surfaces for enhanced retention in the matrix. Mass ratios of whisker:CPC of 1:2, 1:1 and 2:1 were incorporated into a Bis-GMA-based resin and hardened by two-part chemical curing. Composite with only CPC fillers without whiskers served as a control. The specimens were tested using three-point flexure and nano-indentation. Composites with whisker:CPC ratios of 2:1 and 1:1 had flexural strengths (mean+/-SD; n=9) of (164+/-14) MPa and (139+/-22) MPa, respectively, nearly 3 times higher than (54+/-5) MPa of the control containing only CPC fillers (p<0.05). The strength of the new whisker-CPC composites was 3 times higher than the strength achieved in previous studies for conventional bioactive composites containing hydroxyapatite particles in Bis-GMA-based resins. The mechanical properties of the CPC-whisker composites nearly matched those of cortical bone and trabecular bone. Osteoblast-like cell adhesion, proliferation and viability were equivalent on the non-whisker control containing only CPC fillers, on the whisker composite at whisker:CPC of 1:1, and on the tissue culture polystyrene control, suggesting that the new CPC-whisker composite was non-cytotoxic.

3T3 Cells↗

Self-hardening calcium phosphate composite scaffold for bone tissue engineering.

Calcium phosphate cement (CPC) sets 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 craniofacial and orthopaedic repairs. However, its low strength and lack of macroporosity limit its use. This study investigated CPC reinforcement with absorbable fibers, the effects of fiber volume fraction on mechanical properties and macroporosity, and the cytotoxicity of CPC-fiber composite. The rationale was that large-diameter absorbable fibers would initially strengthen the CPC graft, then dissolve to form long cylindrical macropores for colonization by osteoblasts. Flexural strength, work-of-fracture (toughness), and elastic modulus were measured vs. fiber volume fraction from 0% (CPC Control without fibers) to 60%. Cell culture was performed with osteoblast-like cells, and cell viability was quantified using an enzymatic assay. Flexural strength (mean+/-SD; n=6) of CPC with 60% fibers was 13.5+/-4.4 MPa, three times higher than 3.9+/-0.5 MPa of CPC Control. Work-of-fracture was increased by 182 times. Long cylindrical macropores 293+/-46 microm in diameter were created in CPC after fiber dissolution, and the CPC-fiber scaffold reached a macroporosity of 55% and a total porosity of 81%. The new CPC-fiber formulation supported cell adhesion, proliferation and viability. The method of using large-diameter absorbable fibers in bone graft for mechanical properties and formation of long cylindrical macropores for bone ingrowth may be applicable to other tissue engineering materials.

Animals↗

Three-body wear of dental resin composites reinforced with silica-fused whiskers.

OBJECTIVE: Recent studies used silica-fused whiskers to increase the strength and toughness of resin composites. This study investigated the three-body wear of whisker composites. It was hypothesized that the whisker composites would be more wear resistant than composites reinforced with fine glass particles, and the whisker-to-silica filler ratio would significantly affect wear. METHODS: Silica particles were mixed with silicon nitride whiskers at seven different whisker/(whisker + silica) mass fractions (%): 0, 16.7, 33.3, 50, 66.7, 83.3, and 100. Each mixture was heated at 800 degrees C to fuse the silica particles onto the whiskers. Each powder was then silanized and incorporated into a dental resin to make the wear specimens. A four-station wear machine was used with specimens immersed in a slurry containing polymethyl methacrylate beads, and a steel pin was loaded and rotated against the specimen at a maximum load of 76 N. RESULTS: Whisker-to-silica ratio had significant effects (one-way ANOVA; p < 0.001) on wear. After 4 x 10(5) wear cycles, the whisker composite at whisker/(whisker + silica) of 16.7% had a wear scar diameter (mean +/- sd; n = 6) of (643 +/- 39) microm and a wear depth of (82 +/- 19) microm, significantly less than a wear scar diameter of (1184 +/- 34) microm and a wear depth of (173 +/- 15) microm of a commercial prosthetic composite reinforced with fine glass particles (Tukey's multiple comparison). SEM examination revealed that, instead of whiskers protruding from the worn surface, the whiskers were worn with the composite surface, resulting in relatively smooth wear surfaces. SIGNIFICANCE: Silica-fused whisker reinforcement produced dental resin composites that exhibited high resistance to wear with smooth wear surfaces. These properties, together with the strength and fracture toughness being twice those of current glass particle-reinforced composites, may help extend the use of resin composite to large stress-bearing posterior restorations.

Analysis of Variance↗

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↗