Self-setting Calcium Phosphate Cement Research Articles

Different angiogenic abilities of self-setting calcium phosphate cement scaffolds consisting of different proportions of fibrin glue.

To investigate the different angiogenic abilities of the self-setting calcium phosphate cement (CPC) consisting of different proportions of fibrin glue (FG), the CPC powder and the FG solution were mixed at the powder/liquid (P/L) ratios of 1 : 0.5, 1 : 1, and 1 : 2 (g/mL), respectively, and pure CPC was used as a control. After being implanted into the lumbar dorsal fascia of the rabbit, the angiogenic process was evaluated by histological examination and CD31 immunohistochemistry to detect the new blood vessels. The result of the new blood vessel showed that the P/L ratio of 1 : 1 group indicated the largest quantity of new blood vessel at 4 weeks, 8 weeks, and 12 weeks after implantation, respectively. The histological evaluation also showed the best vascular morphology in the 1 : 1 group at 4 weeks, 8 weeks, and 12 weeks after the operation, respectively. Our study indicated that the CPC-FG composite scaffold at the P/L ratio of 1 : 1 (g/mL) stimulated angiopoiesis better than any other P/L ratios and has significant potential as the bioactive material for the treatment of bone defects.

Bone Tissue Engineering: Cell Motility, Vascularization, Micro-Nano Scaffolding, and Remodeling

The treatment of large bone defect still remains a major clinical challenge worldwide. Bone tissue engineering (BTE) strategies have been developed and demonstrated great potential to address this ever-pressing clinical need. The success of BTE strategies requires the synergetic efforts from multidisciplinary research fields including stem cell, biomaterial scaffold, and bioactive growth factor. Furthermore, in order to ensure their clinical efficacy, it is essential to promote rapid vascularization and osteogenesis for higher implant survival rate and to apply favorable mechanical stimulation for better bone tissue remodeling. Reflecting the enormous interest of both our readership and authors in this promising field, we are pleased to present this special issue. This special issue presents a total of 9 papers including research papers and reviews that provide a better understanding of the effects of seed cells, biomaterial scaffolds, bioactive growth factors, mechanical stimulation, and vascularization strategies for the tissue engineered bone (TEB). Osteogenesis is the basic property and the main purpose of the TEB. And the osteogenesis can be achieved by many methods including seed cells, bioactive growth factors, mechanical stimulation, and bioactive composites. In this special issue, V. V. Meretoja et al. report they enhance the osteogenicity of bioactive composites with biomimetic treatment; Y. Chen et al. report the effects of parathyroid hormone on calcium ions in rat bone marrow mesenchymal stem cells and discover the cellular and molecular mechanism of the parathyroid hormone; Y. X. Qin et al. give a review on the mechanotransduction in musculoskeletal tissue regeneration including the effects of fluid flow, loading, and cellular-molecular pathways and provide a better understanding of the mechanical stimulation for bone tissue remodeling. The early osteogenesis in the TEB is mainly the process of endochondral ossification; Y. Yao et al. report the evaluation of insulin medium or chondrogenic medium on proliferation and chondrogenesis of ATDC5 cells to find the better culture medium for the seed cells. Based on the important roles of blood supply and innervations on the nutrition, regulation, and metabolism of the human organs and tissues, G. Pei et al. have given the concept of constructing the highly vascularized and neurotized tissue-engineered bone simultaneously for repairing large bone defects according to the theory of biomimetics in the year of 2000 and firstly prove the scientificity of this concept by successfully constructing the vascularized and neurotized tissue-engineered bone in large animal models such as the goat and rhesus. In this special issue, G. Pei et al. review recent microsurgical techniques used to construct the vascularized and neurotized tissue-engineered bone and also introduce their relevant work. S. Fu et al. report the neuropeptide substance P can improve the osteoblastic and angiogenic differentiation of bone marrow stem cells in vitro, and this result also shows the possible relationship between the nerve system and the bone. J. Xiu et al. report the different angiogenic abilities of self-setting calcium phosphate cement scaffolds consisting of different proportions of fibrin glue and optimize the proportion of fibrin glue to get the best vascularization. The ligament-bone junction of TEB is essential to recover the motor function of the bone defect area when using the TEB for patients. And the silk fibroin is a promising ligament scaffold to achieve this proposal. L. Sun et al. report a novel tissue-engineered ligament-bone junction using the immobilized lentivirus vector bonded on chondroitin sulfate-hyaluronate acid-silk fibroin hybrid scaffold and show the great potentials in future clinical applications. H. Li et al. compare the effect of different thickness of HA-coating on microporous silk scaffolds using alternate soaking technology to determine the best thickness of HA coating to silk scaffolds. Guo-Xian Pei Yi-Xian Qin Dietmar Werner Hutmacher Zhi-Yong Zhang

Development of an in vitro confinement test to predict the clinical handling of polymer-based injectable bone substitutes

The objective of the current study was to present a simple and standardized system as a preliminary attempt to assess the confinement of polymer-based injectable bone substitutes (IBSs) in vitro. Four different types of polymer-based IBSs were selected as model compounds, a thermosensitive collagen gel, a colloidal gelatin gel, a covalently crosslinked oligo(poly(ethylene glycol)fumarate (OPF) gel and a OPF-calcium phosphate composite. A ceramic-based IBS (i.e. a self-setting calcium phosphate cement) was used as reference. The confinement of all IBSs was tested under three different conditions: (1) no flow (as control), (2) dynamic flow after injection and (3) dynamic flow during injection. The results presented herein confirmed that the proposed test can be used to quantify the confinement of various IBSs within artificial defects under static or dynamic flow conditions, thereby offering a potential tool for predictive quantitative determination of the confinement of IBSs in vivo.

Collagen-Calcium Phosphate Cement Scaffolds Seeded with Umbilical Cord Stem Cells for Bone Tissue Engineering

Human umbilical cord mesenchymal stem cells (hUCMSCs) avoid the invasive procedure required to harvest bone marrow MSCs. The addition of collagen fibers into self-setting calcium phosphate cement (CPC) may increase the scaffold strength, and enhance cell attachment and differentiation. The objectives of this study were to develop a novel class of collagen-CPC composite scaffolds, and to investigate hUCMSC attachment, proliferation, and osteogenic differentiation on collagen-CPC scaffolds for the first time. Collagen fibers in CPC improved the load-bearing capability. Flow cytometry showed that the hUCMSCs expressed cell surface markers characteristic of MSCs, and were negative for hematopoietic and endothelial cell markers. hUCMSCs proliferated rapidly in all CPC composite scaffolds, with cell number increasing by sevenfold in 8 days. Cellular function was enhanced with collagen fibers in CPC scaffolds. Cell density increased from (645±60) cells/mm(2) on CPC with 0% collagen, to (1056±65) cells/mm(2) on CPC with 8% collagen (p<0.05). The actin stress fibers inside the hUCMSCs were stained, and the fluorescence intensity was doubled when the collagen in CPC was increased by 0% to 8%. RT-PCR showed that hUCMSCs on CPC with collagen had higher osteogenic expression than those on CPC without collagen. Alizarin Red S staining revealed a great increase in mineralization by hUCMSCs on CPC with collagen than that without collagen. In conclusion, hUCMSCs showed excellent proliferation, differentiation, and synthesis of bone minerals in collagen-CPC composite scaffolds for the first time. The novel hUCMSC-seeded collagen-CPC construct with superior cell function and load-bearing capability is promising to enhance bone regeneration in a wide range of orthopedic and craniofacial applications.

Alginate combined calcium phosphate cements: mechanical properties and in vitro rat bone marrow stromal cell responses

Here, we prepared self-setting calcium phosphate cements (CPCs) based on α-tricalcium phosphate with the incorporation of sodium alginate, and their mechanical properties and in vitro cellular responses were investigated. The addition of alginate enhanced the hardening reaction of CPCs showing shorter setting times within a range of powder-to-liquid ratios. When immersed in a body simulating fluid the alginate-CPCs fully induced a formation of an apatite crystalline phase similar to that of bare CPCs. The compressive and tensile strengths of the CPCs were found to greatly improve during immersion in the fluid, and this improvement was more pronounced in the alginate-CPCs. As a result, the alginate-CPCs retained significantly higher strength values than the bare CPCs after 3-7 days of immersion. The rat bone marrow derived stromal cells (rBMSCs) cultured on the alginate-CPCs initially adhered to and then spread well on the cements surface, showed an on-going increase in the population with culture time, and differentiated into osteoblasts expressing bone-associated genes (collagen type I, osteopontin and bone sialoprotein) and synthesizing alkaline phosphatase. However, the stimulated level of osteogenic differentiation was not confirmative with the incorporation of alginate into the CPC composition based on the results. One merit of the use of alginate was its usefulness in forming CPCs into a variety of scaffold shapes including microspheres and fibers, which is associated with the cross-link of alginate under the calcium-containing solution.

Synergistically reinforcement of a self-setting calcium phosphate cement with bioactive glass fibers

Calcium phosphate cements (CPCs) are highly promising for clinical uses due to their in situ-setting ability, excellent osteoconductivity and bone-replacement capability. However, the low strength limits their uses to non-load-bearing applications. In the present research, first, bioactive glass fibers (BGFs) in the ternary SiO2–CaO–P2O5 system were prepared, and then the fiber composites with compositions based on CPC and BGFs were prepared and characterized. Then, the effect of structure and amount of BGF incorporation into the CPC system, and the effect of mechanical compaction on the fiber-modified system were investigated. The results showed that the compressive strength of the set cements without any BGFs was 0.635MPa which was optimally increased to 3.69MPa by applying 15% BGF and then decreased by further addition of it. In addition, both the work-of-fracture and elastic modulus of the cement were considerably increased after applying the fibers in the cement composition. Also, the setting time slightly decreased by applying the fibers. In summary, processing parameters were tailored to achieve optimum mechanical properties and strength. The prepared composite may be useful in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques.

Rotator Cuff Repair Associated With Large Greater Tuberosity Bone Cysts: A Report of 3 Cases, Surgical Technique, and Review of the Literature

A large greater tuberosity cyst in the location of a symptomatic rotator cuff tear presents a surgical challenge. Little has been published on the management of this complex problem. We report a series of 3 patients, all men aged 42 to 65 years, with symptomatic full-thickness rotator cuff tears. In each case, radiographs revealed the presence of a greater tuberosity bone cyst of at least 2×2 cm, and MRI confirmed a full-thickness rotator cuff tear. Through an open approach, the cyst was localized, decompressed, and packed with a bone graft cement. A standard open repair was utilized to allow better ease of the bone cement placement. After the cement material hardened, anchors were placed and the repair completed. Solid fixation of the rotator cuff tear was obtained in all cases. The postoperative course was uneventful in all patients at 3.5 years (case 1), 14 months (case 2), and 8 months (case 3). All the 3 regained full motion and strength with clinical evidence of rotator cuff healing. Radiographs obtained in the 2 cases with longer-term follow-up showed incorporation of the bone graft material. An open repair using self-setting calcium phosphate cement can offer stability and allow immediate fixation when addressing these cases.

New Generation of Synthetic, Bioresorbable and Injectable Calcium Phosphate Bone Substitute Materials: Alpha-bsm&lt;sup&gt;®&lt;/sup&gt;, Beta-bsm&lt;sup&gt;TM&lt;/sup&gt; and Gamma-bsm&lt;sup&gt;TM&lt;/sup&gt;

Alpha-bsm® is a first generation self-setting, injectable and moldable apatitic calcium phosphate cement (CPC) based on amorphous calcium phosphate (ACP). ACP was prepared using low temperature double decomposition technique, from a calcium solution (0.16 M), and phosphate solution (0.26 M) in a basic (pH~13) media. ACP was than stabilized using three crystal growth inhibitors (CO32-, Mg2+, P2O74-), freeze-dried, and heated (450 °C, 1h) to remove additional moisture and some inhibitors. Dicalcium phosphate dehydrate (DCPD) was also prepared using wet chemistry at room temperature from calcium and phosphate solution, respectively, 0.3 M and 0.15 M. ACP and DCPD powder were combined at a 1:1 ratio and ground to produce Alpha-bsm® bone cement. The cement is supplied as a powder and when mixed with an appropriate amount (0.8 ml/g) of physiological saline at room temperature, forms an injectable putty-like paste. The paste has a working time of about 45 minutes at room temperature, when stored in a moist environment. The setting reaction proceeds isothermically at body temperature (37°C) in less than 20 minutes, forming a hardened, porous (total porosity 50 to 60%), low crystalline (40% comparing with HA), apatitic calcium phosphate cement with a compressive strength range of 10 to 12 MPa. Extensive pre-clinical studies (rabbit radius critical sized defect, canine tibia osteotomy, sheep tibia, primate fibula fracture healing, and primate fibula critical size defect) demonstrate that Alpha-bsm® undergoes remodeling in conjunction with new bone formation. The next generation of Bone Substitute Materials (Beta-bsmTM and Gamma-bsm TM) are formulated based on the Alpha-bsm® chemistry but differ in powder processing (e.g. milling) technique. These materials are also self-setting, injectable and/or moldable apatitic calcium phosphate cements with improved handling and mechanical properties. The setting &amp; hardening reaction of these new CPCs proceeds isothermically in less than 5 minutes at 37°C and once hardened demonstrate a compressive strength of 30 to 50 MPa. The final product (after full conversion) is a low crystalline (40% compared with Hydroxyapatite), calcium deficient (Ca/P atomic ratio = 1.45) carbonated apatite similar to the composition and structure of natural bone mineral (crystal size: length = 26 nm, width thickness = 8 nm). A desirable feature of these cements is their high surface chemistry (with specific surface area of about 180-200 m2/g) which is ideal for remodeling and controlled release of growth factors. A pilot rabbit critically sized femoral defect study comparing the three synthetic family products demonstrate that they share similar remodeling and resorption characteristics up to 52 weeks. Physico-chemical and mechanical performance of these next generation CPCs are favorable when compared with existing CPCs in the market, specifically material working time (at room temperature), cohesivity in a wet environment and fast setting &amp; hardening rate (at body temperature).

Comparison of an experimental bone cement with a commercial control, Hydroset™

Glass polyalkenoate cements based on strontium calcium zinc silicate glasses (Zn-GPCs) and high molecular weight polyacrylic acids (PAA) (MW; 52,000-210,000) have been shown to exhibit mechanical properties and in vitro bioactivity suitable for arthroplasty applications. Unfortunately, these formulations exhibit working times and setting times which are too short for invasive surgical applications such as bone void filling and fracture fixation. In this study, Zn-GPCs were formulated using a low molecular weight PAA (MW; 12,700) and a modifying agent, trisodium citrate dihydrate (TSC), with the aim of improving the rheological properties of Zn-GPCs. These novel formulations were then compared with commercial self-setting calcium phosphate cement, Hydroset, in terms of compressive strength, biaxial flexural strength and Young's modulus, as well as working time, setting time and injectability. The novel Zn-GPC formulations performed well, with prolonged mechanical strength (39 MPa, compression) greater than both vertebral bone (18.4 MPa) and the commercial control (14 MPa). However, working times (2 min) and rheological properties of Zn-GPCs, though improved, require further modifications prior to their use in minimally invasive surgical techniques.

Of the in vivo behavior of calcium phosphate cements and glasses as bone substitutes

The use of injectable self-setting calcium phosphate cements or soluble glass granules represent two different strategies for bone regeneration, each with distinct advantages and potential applications. This study compares the in vivo behavior of two calcium phosphate cements and two phosphate glasses with different composition, microstructure and solubility, using autologous bone as a control, in a rabbit model. The implanted materials were α-tricalcium phosphate cement (cement H), calcium sodium potassium phosphate cement (cement R), and two phosphate glasses in the P 2O 5–CaO–Na 2O and P 2O 5–CaO–Na 2O–TiO 2 systems. The four materials were osteoconductive, biocompatible and biodegradable. Radiological and histological studies demonstrated correct osteointegration and substitution of the implants by new bone. The reactivity of the different materials, which depends on their solubility, porosity and specific surface area, affected the resorption rate and bone formation mainly during the early stages of implantation, although this effect was weak. Thus, at 4 weeks the degradation was slightly higher in cements than in glasses, especially for cement R. However, after 12 weeks of implantation all materials showed a similar degradation degree and promoted bone neoformation equivalent to that of the control group.

Injectable and strong nano-apatite scaffolds for cell/growth factor delivery and bone regeneration

Objectives Seven million people suffer bone fractures each year in the U.S., and musculoskeletal conditions cost $215 billion/year. The objectives of this study were to develop moldable/injectable, mechanically strong and in situ-hardening calcium phosphate cement (CPC) composite scaffolds for bone regeneration and delivery of osteogenic cells and growth factors. Methods Tetracalcium phosphate [TTCP: Ca 4(PO 4) 2O] and dicalcium phosphate (DCPA: CaHPO 4) were used to fabricate self-setting calcium phosphate cement. Strong and macroporous scaffolds were developed via absorbable fibers, biopolymer chitosan, and mannitol porogen. Following established protocols, MC3T3-E1 osteoblast-like cells (Riken, Hirosaka, Japan) were cultured on the specimens and inside the CPC composite paste carrier. Results The scaffold strength was more than doubled via reinforcement ( p < 0.05). Relationships and predictive models were established between matrix properties, fibers, porosity, and overall composite properties. The cement injectability was increased from about 60% to nearly 100%. Cell attachment and proliferation on the new composite matched those of biocompatible controls. Cells were able to infiltrate into the macropores and anchor to the bone mineral-like nano-apatite crystals. For cell delivery, alginate hydrogel beads protected cells during cement mixing and setting, yielding cell viability measured via the Wst-1 assay that matched the control without CPC ( p > 0.1). For growth factor delivery, CPC powder:liquid ratio and chitosan content provided the means to tailor the rate of protein release from CPC carrier. Significance New CPC scaffolds were developed that were strong, tough, macroporous and osteoconductive. They showed promise for injection in minimally invasive surgeries, and in delivering osteogenic cells and osteoinductive growth factors to promote bone regeneration. Potential applications include various dental, craniofacial, and orthopedic reconstructions.

Preparation of porous apatite granules from calcium phosphate cement

A versatile method for preparing spherical, micro- and macroporous (micro: 2-10 and macro: 150-550 microm pores), carbonated apatitic calcium phosphate (Ap-CaP) granules (2-4 mm in size) was developed by using NaCl crystals as the porogen. The entire granule production was performed between 21 and 37 degrees C. A CaP cement powder, comprising alpha-Ca3(PO4)2 (61 wt.%), CaHPO4 (26%), CaCO3 (10%) and precipitated hydroxyapatite, Ca10(PO4)6(OH)2 (3%), was dry mixed with NaCl crystals varying in size from 420 microm to 1 mm. Cement powder (35 wt.%) and NaCl (65 wt.%) mixture was kneaded with an ethanol-Na2HPO4 initiator solution, and the formed dough was immediately agitated on an automatic sieve shaker for a few minutes to produce the spherical granules. Embedded NaCl crystals were then leached out of the granules by soaking them in deionized water. CaP granules were micro- and macroporous with a total porosity of 50% or more. Granules were composed of carbonated, poorly crystallized, apatitic CaP phase. These were the first spherical and porous CaP granules ever produced from a self-setting calcium phosphate cement. The granules reached their final handling strength at the ambient temperature through the cement setting reaction, without having a need for sintering.

Self-Setting Biphase Porous Calcium Phosphate Cement

This work has achieved a novel self-setting biphase porous calcium phosphate cement (CPC). This biphase porous CPC is mainly formed by α-tricalcium phosphate (α-TCP) and β-tricalcium phosphate (β-TCP). The influence of the weight percent (wt%) of β-TCP of the powder was studied. The setting time is mainly 10-30min, and increasing with the weight percent of β-TCP. Powder ray diffraction (XRD) analysis showed that most α-TCP have turned to low-crystallinized HA after immersed in Simulated Body Fluid (SBF) of 37°C for 7 days. SEM observation showed that the resultants are mainly formed with micropores and microcrystallites, and more micropores turned out in cements with more β-TCP after immersed in SBF for 8 weeks.

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.

Polymer--calcium phosphate cement composites for bone substitutes.

The use of self-setting calcium phosphate cements (CPCs) as bioresorbable bone-replacement implant materials presently is limited to non-load-bearing applications because of their low compressive strength relative to natural bone. The present study investigated the possibility of strengthening a commercially available CPC, alpha-BSM, by incorporating various water-soluble polymers into the cement paste during setting. Several polyelectrolytes, poly(ethylene oxide), and the protein bovine serum albumin (BSA) were added in solution to the cement paste to create calcium phosphate-polymer composites. Composites formulated with the polycations poly(ethylenimine) and poly(allylamine hydrochloride) exhibited compressive strengths up to six times greater than that of pure alpha-BSM material, with a maximum value reached at intermediate polymer content and for the highest molecular weight studied. Composites containing BSA developed compressive strengths twice that of the original cement at protein concentrations of 13-25% by weight. In each case, XRD studies correlate the improvement in compressive strength with reduced crystallite dimensions, as evidenced by a broadening of the (0,0,2) reflection. This suggests that polycation or BSA adsorption inhibits crystal growth and possibly leads to a larger crystal aspect ratio. SEM results indicate a denser, more interdigitated microstructure. The increased strength was attributed to the polymer's capacity to bridge between multiple crystallites (thus forming a more cohesive composite) and to absorb energy through plastic flow.

Effects of fiber length and volume fraction on the reinforcement of calcium phosphate cement.

A self-setting calcium phosphate cement (CPC) transforms into solid hydroxyapatite during setting at body temperature, and has been used in a number of medical and dental procedures. However, the inferior mechanical properties of CPC prohibits its use in unsupported defects, stress-bearing locations or reconstruction of thin bones. The aim of the present study was to strengthen CPC with fiber reinforcement, to examine the effect of fiber length and volume fraction, and to investigate the reinforcement mechanisms. Previous studies employed either short fibers for random distributions, or continuous fibers that were as long as the specimen size with preferred orientations such as unidirectional alignment. In the present study, a novel methodology was developed in which fibers several times longer than the specimen mold size were randomly mixed with the CPC paste to approximate the isotropy associated with short fibers, and at the same time achieve the high reinforcement efficacy associated with continuous fibers. Carbon fibers of 8 microm diameter were used with fiber lengths ranging from 3 mm to 200 mm, and fiber volume fraction from 1.9% to 9.5%. A three-point flexural test was used to fracture the specimens. Scanning electron microscopy was used to examine crack-fiber interactions and specimen fracture surfaces. The composite containing fibers of 75 mm in length at a volume fraction of 5.7% achieved a flexural strength about 4 times, and work-of-fracture 100 times, greater than the unreinforced CPC. It is concluded that randomly mixing the CPC paste with carbon fibers that were several times longer than the specimen mold size resulted in substantial improvements in strength and fracture resistance; the reinforcement mechanisms were crack bridging and fiber pullout; and fiber length and volume fraction were key microstructural parameters that determined the cement properties.

Strong and macroporous calcium phosphate cement: Effects of porosity and fiber reinforcement on mechanical properties.

Because of its excellent osteoconductivity and bone-replacement capability, self-setting calcium phosphate cement (CPC) has been used in a number of clinical procedures. For more rapid resorption and concomitant osseointegration, methods were desired to build macropores into CPC; however, this decreased its mechanical properties. The aims of this study, therefore, were to use fibers to strengthen macroporous CPC and to investigate the effects of the pore volume fraction on its mechanical properties. Water-soluble mannitol crystals were incorporated into CPC paste; the set CPC was then immersed in water to dissolve mannitol, producing macropores. Mannitol/(mannitol + CPC powder) mass fractions of 0, 10, 20, 30, and 40% were used. An aramid fiber volume fraction of 6% was incorporated into the CPC-mannitol specimens, which were set in 3 mm x 4 mm x 25 mm molds and then fractured in three-point flexure to measure the strength, work of fracture, and modulus. The dissolution of mannitol created well-formed macropores, with CPC at 40% mannitol having a total porosity of a 70.8% volume fraction. Increasing the mannitol content significantly decreased the properties of CPC without fibers (analysis of variance; p < 0.001). The strength (mean +/- standard deviation; n = 6) of CPC at 0% mannitol was 15.0 +/- 1.8 MPa; at 40% mannitol, it decreased to 1.4 +/- 0.4 MPa. Fiber reinforcement improved the properties, with the strength increasing threefold at 0% mannitol, sevenfold at 30% mannitol, and nearly fourfold at 40% mannitol. The work of fracture increased by 2 orders of magnitude, but the modulus was not changed as a result of fiber reinforcement. A scanning electron microscopy examination of specimens indicated crack deflection and bridging by fibers, matrix multiple cracking, and frictional pullout of fibers as the reinforcement mechanisms. Macroporous CPCs were substantially strengthened and toughened via fiber reinforcement. This may help extend the use of CPCs with macropores for bony ingrowth to the repair of larger defects in stress-bearing locations.

Effect of mechanical grinding of MCPM and CaO mixtures on their composition and on the mechanical properties of the resulting self-setting hydraulic calcium phosphate cements.

Calcium bis-dihydrogenophosphate monohydrate (or monocalcium phosphate monohydrate, MCPM) is often used as the acid calcium phosphate in hydraulic calcium phosphate cement formulations. But commercial MCPM is not pure; it contains a small amount of orthophosphoric acid and moisture. Consequently, MCPM is difficult to mill and the powder is sticky and presents aggregates. Because granularity influences the mechanical properties of the hardened cements, a possible way to get around this difficulty that has been proposed is to premix it with other materials before grinding. We therefore ground commercial MCPM with CaO. A rapid decrease in the amount of MCPM was observed during mechanical grinding by a solid-solid reaction with calcium oxide. The final products were anhydrous or dihydrate dicalcium phosphate and/or hydroxyapatite or calcium-deficient hydroxyapatite depending on the initial calcium-to-phosphate (Ca/P) ratio. The mechanical properties (compressive strength and setting time) of cements made from MCPM and CaO were affected whatever the Ca/P ratio as a consequence of the change in composition of the starting materials. Storage at different temperatures of MCPM and CaO mixtures manually ground in a mortar for only 2 min and without mechanical grinding did not affect their composition, but a decrease was observed in the compressive strength of cements made from these mixtures.

Osseointegration of composite calcium phosphate bioceramics

The resistance of macroporous calcium phosphate ceramics to compressive strength generally is low and depends on, among other factors, porosity percentage and pore size. A compromise always is adopted between high porosity, required for a good integration, and mechanical strength, which increases with material density. We improved the strength of macroporous calcium phosphate ceramics of interconnected porosity by filling the pores with a highly soluble, self-setting calcium phosphate cement made of TCP and DCPD. Cylinders of the resulting material were implanted in sheep condyles and subjected to histological analysis after 20, 60, and 120 days. Microradiographs were made of the histological sections. The control material consisted of ceramic that had not been loaded with cement. Progressive ingrowth of bone into the ceramic pores occurred as the cement was degraded during the first implantation period. Marked degradation of the cement was apparent after 2 months, with fragmentation of the cement in most of the pores and the presence of bone tissue between the fragments. All the cement had been replaced by bone after 4 months. Some fragments of cement still were embedded in the newly formed bone. There was no significant difference between the integration of loaded and nonloaded ceramics. Filling the macroporous ceramic pores with a calcium phosphate cement significantly improved the mechanical strength of these ceramics without modifying their integration in the healing bone.

Minimally invasive bone harvesting tools.

The most readily available source for autologous bone graft used in spinal fusion (the gold standard) is the iliac crest. However, the open surgical approach for harvesting corticocancellous iliac bone is associated with a marked increase in morbidity. This study suggests two alternatives to the traditional open harvesting procedure. For anterior interbody fusion procedures using a cage, the autologous bone is harvested regionally from a neighboring vertebral body. Alternatively, using minimally invasive techniques, a custom bone graft harvester with a flexible tube and cutting tip allows harvesting of autologous bone from a single entry point at the iliac crest. The effect on the mechanical strength of a lumbar vertebra of removing a cylindrical regional bone graft was studied in a cadaveric model. The bone defect was filled using three different filler materials: a porous tri-calcium phosphate plug, a porous tantalum plug, and a self-setting calcium phosphate cement. After plug removal, the vertebral body's strength in flexion/compression loading was reduced significantly, but could be restored to at least intact values with any of the three filler materials. The minimally invasive bone graft harvester was tested in three cadaveric pelves. With the cutting tip being guided within the cortical boundaries of the pelvis, cancellous bone volumes of 10-20 cc could be harvested from each iliac bone. Regional bone graft harvest in anterior spine surgery is suggested to be anatomically safe and biomechanically acceptable. Any of the three filler materials can restore the vertebral body's mechanical strength, but the filler's long-term resorption/remodeling or osteointegration behavior is unknown. The minimally invasive bone graft harvester is a novel tool, which performed satisfactorily under laboratory conditions, but clinical results are still missing.