Porous polymer/bioactive glass composites for soft-to-hard tissue interfaces

Porous composites consisting of a polysulfone (or cellulose acetate) matrix and bioactive glass particles were prepared by phase separation techniques. Microstructures were designed for potential application as an interconnect between artificial cartilage and bone. The effects of polymer type, concentration and molecular weight, as well as bioactive glass size and content, on the microstructures of the composites were studied. The composites have asymmetric structures with dense top layers and porous structures beneath. The microstructural features depend most strongly on the type of polymer, the interaction between the polymer and bioactive glass, and the glass content. The dense top layer could be removed by abrasion to make a structure with large pores (20-150 microm) exposed. Composites were immersed in simulated body fluid at body temperature. The growth of hydroxycarbonate apatite inside and on the composites demonstrates their potential for integration with bone. Composite modulus and break strength increased with increasing glass content due to the change in composition and pore content.     

Bioactive composites consisting of PEEK and calcium silicate powders

Bioactive bone-repairing materials with mechanical properties analogous to those of natural bone can be obtained through the combination of bioactive ceramic fillers with organic polymers. Previously, we developed novel bioactive microspheres in a binary CaO-SiO2 system produced through a sol-gel process as filler for the fabrication of composites. In this study, we fabricate bioactive composites in which polyetheretherketone is reinforced with 0-50 vol% 30CaO x 70SiO2 (CS) microspheres. The prepared composites reinforced with CS particles form hydroxyapatite on their surfaces in simulated body fluid. The induction periods of hydroxyapatite formation on the composites decrease with increasing amount of CS particles. The mechanical properties of the composites are evaluated by three-point bending test. The composites reinforced with 20 vol% CS particles show 123.5 MPa and 6.43 GPa in bending strength and Young's modulus, respectively.     

Degradation, Bioactivity, and Osteogenic Potential of Composites Made of PLGA and Two Different Sol�CGel Bioactive Glasses

We have developed poly(L: -lactide-co-glycolide) (PLGA) based composites using sol-gel derived bioactive glasses (S-BG), previously described by our group, as composite components. Two different composite types were manufactured that contained either S2-high content silica S-BG, or A2-high content lime S-BG. The composites were evaluated in the form of sheets and 3D scaffolds. Sheets containing 12, 21, and 33?vol.% of each bioactive glass were characterized for mechanical properties, wettability, hydrolytic degradation, and surface bioactivity. Sheets containing A2 S-BG rapidly formed a hydroxyapatite surface layer after incubation in simulated body fluid. The incorporation of either S-BG increased the tensile strength and Young's modulus of the composites and tailored their degradation rates compared to starting compounds. Sheets and 3D scaffolds were evaluated for their ability to support growth of human bone marrow cells (BMC) and MG-63 cells, respectively. Cells were grown in non-differentiating, osteogenic or osteoclast-inducing conditions. Osteogenesis was induced with either recombinant human BMP-2 or dexamethasone, and osteoclast formation with M-CSF. BMC viability was lower at higher S-BG content, though specific ALP/cell was significantly higher on PLGA/A2-33 composites. Composites containing S2 S-BG enhanced calcification of extracellular matrix by BMC, whereas incorporation of A2 S-BG in the composites promoted osteoclast formation from BMC. MG-63 osteoblast-like cells seeded in porous scaffolds containing S2 maintained viability and secreted collagen and calcium throughout the scaffolds. Overall, the presented data show functional versatility of the composites studied and indicate their potential to design a wide variety of implant materials differing in physico-chemical properties and biological applications. We propose these sol-gel derived bioactive glass-PLGA composites may prove excellent potential orthopedic and dental biomaterials supporting bone formation and remodeling.     

多孔羟基磷灰石生物陶瓷的合成和特性研究进展

人体骨组织的多孔结构，有利于骨组织生长代谢所需物质的交流，并能很好地适应外部应力的变化。合成模拟骨组织多孔结构的生物活性陶瓷材料，用于临床人体骨组织缺失的修复，是组织工程所需要的。将化学沉淀法合成的羟基磷灰石原始粉末与过氧化氢、降乙烯醇、甲基纤维素等孔成孔物质混合，经低温发泡，中温脱碳，高温烧结，可以获得孔径理想，互通性能良好的多孔羟基磷灰石陶瓷。这种陶瓷，在一定程度上具有骨诱导性能，但更重要的是它能够很好的吸附人体骨形成蛋白等骨生长因子，使其具有良好的骨再生能力，从而获得了良好的临床应用性能。本文从临床应用性能的角度，评述了近几年多孔羟基磷灰石生物陶瓷的研究进展。     

Processing and properties of porous poly(L-lactide)/bioactive glass composites

Porous poly(L-lactide)/bioactive glass (PLLA/BG) composites were prepared by phase separation of polymer solutions containing bioactive glass particles (average particle size: 1.5 microm). The composite microstructures consist of a porous PLLA matrix with glass particles distributed homogeneously throughout. Large pores (>100 microm) are present in a network of smaller (<10 microm) interconnected pores. The porous microstructure of the composites was not significantly influenced by glass content (9 or 29 vol%), but silane pretreatment of the glass resulted in better glass incorporation in the matrix. Mechanical tests showed that an increase in glass content increased the elastic modulus of the composites, but decreased their tensile strength and break strain. Silane pretreatment enhanced the increase in modulus and prevented the decrease in tensile strength with increasing glass content. Composites soaked in simulated body fluid (SBF) at body temperature formed bone-like apatite inside and on their surfaces. The silane pretreatment of glass particles delayed the in vitro apatite formation. This bone-like apatite formation demonstrates the composites' potential for integration with bone.     

The behavior of novel hydrophilic composite bone cements in simulated body fluids

Composite bone cements were formulated with bioactive glass (MgO--SiO(2)--3CaO. P(2)O(5)) as the filler and hydrophilic matrix. The matrix was composed of a starch/cellulose acetate blend (SCA) as the solid component and a mixture of methylmethacrylate/acrylic acid (MMA/AA) as the liquid component. The curing parameters, mechanical properties, and bioactive behavior of these composite cements were determined. The addition of up to 30 wt % of glass improved both compressive modulus and yield strength and kept the maximum curing temperature at the same value presented by a typical acrylic-based commercial formulation. The lack of a strongly bonded interface (because no coupling agent was used) had important effects on the swelling and mechanical properties of the novel bone cements. However, bone cements containing AA did not show a bioactive behavior, because of the deleterious effect of this monomer on the calcium phosphate precipitation on the polymeric surfaces. Formulations without AA were prepared with MMA or 2-hydroxyethyl methacrylate (HEMA) as the liquid component. Only these formulations could form an apatite-like layer on their surface. These systems, therefore, are very promising: They are bioactive, hydrophilic, partially degradable, and present interesting mechanical properties. This combination of properties could facilitate the release of bioactive agents from the cement, allow bone ingrowth in the cement, and induce a press-fitting effect, improving the interfaces with both the prosthesis and the bone.     

Self-reinforced composites of bioabsorbable polymer and bioactive glass with different bioactive glass contents. Part II: In vitro degradation

The in vitro degradation behavior of self-reinforced bioactive glass-containing composites was investigated comparatively with plain self-reinforced matrix polymer. The materials used were spherical bioactive glass 13-93 particles, with a particle size distribution of 50-125 microm, as a filler material and bioabsorbable poly-L,DL-lactide 70/30 as a matrix material. The composites containing 0, 20, 30, 40 and 50 wt.% of bioactive glass were manufactured using twin-screw extruder followed by self-reinforcing. The samples studied were characterized determining the changes in mechanical properties, thermal properties, molecular weight, mass loss and water absorption in phosphate-buffered saline at 37 degrees C for up to 104 weeks. The results showed that the bioactive glass addition modified the degradation kinetics and material morphology of the matrix material. It was concluded that the optimal bioactive glass content depends on the applications of the composites. The results of this study could be used as a guideline when estimating the best filler content of other self-reinforced osteoconductive filler containing composites which are manufactured in a similar way.     

Bioactive glass/polymer composite materials with mechanical properties matching those of cortical bone

Stress shielding resulting from mismatch in dynamic mechanical properties contributes to the reduced stability of osseous implants. Our objective was to develop biocompatible composites having mechanical properties similar to those of cortical bone. Polymers of urethane dimethacrylate (UDMA) and 2-hydroxyethyl methacrylate (HEMA, 0-20%) and composites containing bioactive glass particles (70% SiO(2), 25% CaO, and 5% P(2)O(5)), with or without silane treatment were prepared. Young's moduli of composites containing silane-treated glass (16 GPa) were significantly greater than those of composites containing untreated glass (12-13 GPa) or of unfilled polymers (5-6 GPa). Bioactive glass reduced water sorption by the composites and incorporation of silane-treated glass prevented HEMA-induced increases in water sorption. Osteoblast-like cells attached equally well to UDMA polymer and composite containing silane-treated bioactive glass. Thus, silane treatment improved the mechanical properties of bioactive glass composites without compromising biocompatibility. This material has a Young's modulus comparable to that of cortical bone. Therefore, silane-treated bioactive glass composites, when used as implant or cement materials, would reduce stress shielding and improve implant stability.     

Promotion of bone formation using highly pure porous beta-TCP combined with bone marrow-derived osteoprogenitor cells

Beta-tricalcium phosphate (TCP) exhibits rapid degradation and weak mechanical properties, which has limited its application as bone graft substitutes, though it has good biocompatibility and osteoconductivity. We hypothesized that a composite of highly pure porous beta-TCP and bone marrow-derived osteoprogenitor cells (BMO) could improve bone formation, and slow down the degradation of beta-TCP. A highly pure porous beta-TCP with 75% porosity was fabricated. The pores averaged 200-400 microm in diameter, with interconnecting paths 100-200 microm. Blocks of beta-TCP 5 mm3 were combined with BMO, and incubated 2 weeks with (+) or without (-) osteogenic medium. They were then implanted into subcutaneous sites of syngeneic rats for 24 weeks. These composites were harvested at different time points. The alkaline phosphatase activity and bone osteocalcin content of the composites (+) were much higher than corresponding values in the composites (-) of the control group (p<0.01). Light microscopy revealed mature bone and lots of blood vessels only in the TCP/BMO composite (+). The amount of newly formed bone increased until week 24. Slow resorptive activity could be found. The mechanical parameters of the composites were much improved over those of dry beta-TCP blocks. These results showed that tissue engineering treatment on incubating the composites of beta-TCP and BMO cells in osteogenic medium results in a good osteogenic activity.     

Novel bioactive materials with different mechanical properties

Some ceramics, such as Bioglass, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously bond to living bone. They are called bioactive materials and are already clinically used as important bone substitutes. However, compared with human cortical bone, they have lower fracture toughness and higher elastic moduli. Therefore, it is desirable to develop bioactive materials with improved mechanical properties. All the bioactive materials mentioned above form a bone-like apatite layer on their surfaces in the living body, and bond to bone through this apatite layer. The formation of bone-like apatite on artificial material is induced by functional groups, such as Si-OH, Ti-OH, Zr-OH, Nb-OH, Ta-OH, -COOH, and PO(4)H(2). These groups have specific structures revealing negatively charge, and induce apatite formation via formations of an amorphous calcium compound, e.g., calcium silicate, calcium titanate, and amorphous calcium phosphate. These fundamental findings provide methods for preparing new bioactive materials with different mechanical properties. Tough bioactive materials can be prepared by the chemical treatment of metals and ceramics that have high fracture toughness, e.g., by the NaOH and heat treatments of titanium metal, titanium alloys, and tantalum metal, and by H(3)PO(4) treatment of tetragonal zirconia. Soft bioactive materials can be synthesized by the sol-gel process, in which the bioactive silica or titania is polymerized with a flexible polymer, such as polydimethylsiloxane or polytetramethyloxide, at the molecular level to form an inorganic-organic nano-hybrid. The biomimetic process has been used to deposit nano-sized bone-like apatite on fine polymer fibers, which were textured into a three-dimensional knit framework. This strategy is expected to ultimately lead to bioactive composites that have a bone-like structure and, hence, bone-like mechanical properties.     

Bioactive nano-titania ceramics with biomechanical compatibility prepared by doping with piezoelectric BaTiO3

Piezoelectric BaTiO₃ was employed as a crystal growth inhibitor additive for the preparation of bioactive nano-titania ceramics in this study. It is found that the additive could significantly inhibit nano-titania ceramic crystal growth during the pressureless sintering process. This inhibitory ability has great effects on the mechanical properties and bioactivities of the nano-titania ceramics, making it possible to obtain bioactive nano-titania ceramics with mechanical properties analogous to human bone. In this study, the crystal grain sizes of the nano-titania ceramics ranged from 18 to 68 nm and the particle sizes ranged from 187 to 580 nm by changing the additive content from 1% to 20%. The elastic modulus of the nano-titania ceramics ranged from 6.2 to 10.6 GPa, which is analogous to that of human bone, by adjusting the additive content. The piezoelectric properties of the additive also showed the enhancing effects on the bioactivity of the nano-titania ceramics, which made the osteoblasts proliferate faster on the nano-titania ceramics in cell culture experiments. It might be a potential way to prepare bioactive nano-titania ceramics with biomechanical compatibility by using BaTiO₃ as a crystal growth inhibitor.     

Production of ultra-fine bioresorbable carbonated hydroxyapatite

Ionic-substituted hydroxyapatite (HAp) based materials may be a better choice than pure HAp owing to their similarity in chemical composition with biological apatite. The present study reports a process for the production of carbonated hydroxyapatite (CHAp) using microwaves. The CHAp was evaluated for its phase purity, chemical homogeneity, functionality, morphology, and solubility. The CHAp thus obtained was compared with a pure HAp and a biological apatite, which provides quite an interesting insight into the carbonate substitution. The in vitro ionic dissolution rates determined under physiological conditions clearly demonstrate the soluble nature of CHAp compared to HAp. The overall results indicate that the processed CHAp has increased resorption relative to pure HAp and has a chemical composition corresponding to some extent with that of biological apatite.     

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.     

Influence of physicochemical reactions of bioactive glass on the behavior and activity of human osteoblasts in vitro

Bioactive glasses are characterized by a bond to bone with a hydroxyl carbonate apatite layer. They enhance bone tissue formation and for this purpose are used in orthopedic surgery and in dental implantology. In the current work, we studied the biological response of human osteoblasts with a bioactive glass. This bioactive glass is based on 50% Si0(2), 20% Na(2)O, 16% CaO, 6% P(2)O(5), 5% K(2)0, 2% Al(2)O(3) and 1% MgO and designated A9. Cracks and irregularities were observed on the material surface when it was immersed in the culture medium. In addition, energy dispersive X-ray analyses highlighted a selective release of the elements at the surface of the bioactive glass, such as Na(+) and K(+) ions, released from the first day, contrary to the Si, Al, Ca, P, and Mg elements, which were released more slowly. Cell proliferation kinetics, total protein synthesis, and DNA content of the osteoblasts in contact with bioactive glass were similar to control cells. The morphological studies by light and scanning electron microscopy revealed an increasing cellular density in culture with bioactive glass without contact inhibition. The immunohistochemical studies highlighted the expression of types I, III, and V collagens by osteoblasts cultured in the presence of bioactive glass. The pH measurement of the culture medium in the presence of bioactive glass demonstrated a slight alkalinization. We thus conclude that human osteoblasts preserve their properties in the presence of bioactive glass (A9).     

Development of a bioactive glass fiber reinforced starch-polycaprolactone composite

For bone regeneration and repair, combinations of different materials are often needed. Biodegradable polymers are often combined with osteoconductive materials, such as bioactive glass (BaG), which can also improve the mechanical properties of the composite. The aim of this work was to develop and characterize BaG fiber reinforced starch-poly-epsilon-caprolactone (SPCL) composite. Sheets of SPCL (30/70 wt %) were produced using single-screw extrusion. They were then cut and compression-molded in layers with BaG fibers to form composite structures with different combinations. Mechanical and degradation properties of the composites were studied. The actual amount of BaG in the composites was determined using combustion tests. Initial mechanical properties of the reinforced composites were at least 50% better than the properties of the nonreinforced specimens. However, the mechanical properties of the composites after 2 weeks of hydrolysis were comparable to those of the nonreinforced samples. During the 6 weeks hydrolysis the mass of the composites had decreased only by about 5%. The amount of glass in the composites remained as initial for the 6-week period of hydrolysis. In conclusion, it is possible to enhance initial mechanical properties of SPCL by reinforcing it with BaG fibers. However, mechanical properties of the composites are typical for bone fillers and strength properties need to be further improved for allowing more demanding bone applications.     

Self-reinforced composites of bioabsorbable polymer and bioactive glass with different bioactive glass contents. Part I: Initial mechanical properties and bioactivity

Spherical bioactive glass 13-93 particles, with a particle size distribution of 50-125 microm, were combined with bioabsorbable poly-L,DL-lactide 70/30 using twin-screw extrusion. The composite rods containing 0, 20, 30, 40 and 50 wt% of bioactive glass were further self-reinforced by drawing to a diameter of approximately 3 mm. The bioactive glass spheres were well dispersed and the open pores were formed on the composite surface during drawing. The initial mechanical properties were studied. The addition of bioactive glass reduced the bending strength, bending modulus, shear strength, compression strength and torsion strength of poly-L,DL-lactide. However, the strain at maximum bending load increased in self-reinforced composites. Initially brittle composites became ductile in self-reinforcing. The bioactivity was studied in phosphate buffered saline for up to 12 days. The formation of calcium phosphate precipitation was followed using scanning electron microscopy and energy dispersive X-ray analysis. Results showed that the bioactive glass addition affected the initial mechanical properties and bioactivity of the composites. It was concluded that the optimal bioactive glass content depends on the applications of the composites.     

Beta-CaSiO3/beta-Ca3(PO4)2 composite materials for hard tissue repair: in vitro studies

In this study, a series of beta-CaSiO(3) (CS)/beta-Ca(3)(PO(4))(2) (TCP) composites with different ratios were prepared to produce new bioactive and biodegradable biomaterials for potential bone repair. The mechanical properties of CS-TCP composites increased steadily with the increase of TCP amounts in composites. Formation of bone-like apatite on a range of CS-TCP composites with CS weight percentage ranging from 0 to 100 has been investigated in simulated body fluid (SBF). The presence of bone-like apatite layer on the composite surface after soaking in SBF was demonstrated by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and fourier transform infrared reflection spectroscopy (FTIR). The results showed that the apatite formation ability of the CS-TCP composite was enhanced with increasing CS content in the composites. For composites with more than 50% CS contents, the samples were completely covered by a layer of dense bone-like apatite just after 3 days immersion. Dissolution tests in Tris-HCl buffer solution showed obvious differences with different CS contents in composites. The dissolution rate increased with the increase of CS content, which suggested that the solubility of biphasic composites could be tailored by adjusting the initial CS/TCP ratio. In vitro cell experiments showed that higher content of CS phase in composites promoted cell proliferation and differentiation. When the CS amount in the composite increased to 50%, the proliferation rate and ALP activities of osteoblast-like cells showed significant difference compared with pure TCP (p < 0.05). Results of the study suggested that the CS-TCP composites with more than 50% CS content might be promising bone repair materials.     

Novel porous hydroxyapatite prepared by combining H2O2 foaming with PU sponge and modified with PLGA and bioactive glass

Porous hydroxyapatite (HA) scaffolds have been intensively studied and developed for bone tissue engineering, but their mechanical properties remain to be improved. The aim of this study is to prepare HA-based composite scaffolds that have a unique macroporous structure and special struts of a polymer/ceramic interpenetrating composite and a bioactive coating. A novel combination of a polyurethane (PU) foam method and a hydrogen peroxide (H(2)O( 2)) foaming method is used to fabricate the macroporous HA scaffolds. Micropores are present in the resulting porous HA ceramics after the unusual sintering of a common calcium phosphate cement and are infiltrated with the poly(D,L-lactic-co-glycolic acid) (PLGA) polymer. The internal surfaces of the macropores are further coated with a PLGA-bioactive glass composite coating. The porous composite scaffolds are characterized in terms of microstructure, mechanical properties, and bioactivity. It is found that the HA scaffolds fabricated by the combined method show high porosities of 61-65% and proper macropore sizes of 200-600 microm. The PLGA infiltration improved the compressive strengths of the scaffolds from 1.5-1.8 to 4.0-5.8 MPa. Furthermore, the bioactive glass-PLGA coating rendered a good bioactivity to the composites, evidenced by the formation of an apatite layer on the sample surfaces immersed in the simulated body fluid (SBF) for 5 days. The porous HA-based composites obtained from this study have suitable porous structures, proper mechanical properties, and a high bioactivity, and thus finds potential application as scaffolds for bone tissue engineering.     

Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty

Clinical outcome of cemented implants to revision total hip replacement (THR) is not as satisfactory as primary THR, due to the loss of bone stock and normal trabecular pattern. This study evaluated a bioactive bone cement, strontium-containing hydroxyapatite (Sr-HA) bone cement, in a goat revision hip hemi-arthroplasty model, and compared outcomes with polymethylmethacrylate (PMMA) bone cement. Nine months after operation, significantly higher bonding strength was found in the Sr-HA group (3.36+/-1.84 MPa) than in the PMMA bone cement group (1.23+/-0.73 MPa). After detached from the femoral component, the surface of PMMA bone cement mantle was shown relatively smooth, whereas the surface of the Sr-HA bioactive bone cement mantle was uneven, by SEM observation. EDX analysis detected little calcium and no phosphorus on the surface of PMMA bone cement mantle, while high content of calcium (14.03%) and phosphorus (10.37%) was found on the surface of the Sr-HA bone cement mantle. Even higher content of calcium (17.37%) and phosphorus (10.84%) were detected in the concave area. Intimate contact between Sr-HA bioactive bone cement and bone was demonstrated by histological and SEM observation. New bone bonded to the surface of Sr-HA cement and grew along its surface. However, fibrous tissue was observed between PMMA bone cement and bone. The results showed good bioactivity of Sr-HA bioactive bone cement in this revision hip replacement model using goats. This in vivo study also suggested that Sr-HA bioactive bone cement was superior to PMMA bone cement in terms of bone-bonding strength. Use of bioactive bone cement may be a possible solution overcoming problems associated with the use of PMMA bone cement in revision hip replacement.