Key Engineering Materials Vols. 330-332

Abstract: Controlled release silica sol-gels are room temperature processed, porous, resorbable, and biocompatible materials. Many molecules including drugs, proteins, and growth factors can be released from sol-gels, and the quantity and duration of the release can vary widely. Processing parameters render these release properties exquisitely versatile [1]. The synthesis of controlled release sol-gels involves several steps: an acid-catalyzed hydrolysis to form a sol with the molecules included, followed by casting, aging, and drying. Additional steps such as grinding and sieving are required to produce sol-gel granules of a desirable size. In this study, we focus on the synthesis of controlled release sol-gel microspheres by using a novel process, which involves only two steps:sol formation followed by emulsification. Sol-gel microspheres containing either vancomycin (antibiotic) or bupivacaine (analgesic) were successfully synthesized via this synthesis route. Both drugs showed controlled, load-dependent and time-dependent release from the microspheres. The in vitro release properties of sol-gel microspheres were different from those of sol-gel granules produced by grinding and sieving. In comparison to a fast, short-term release from the granules, the release from the microspheres was slower and of longer duration. In addition, the degradation rate of microspheres was significantly slower than that of the granules. These data enable the use of sol-gel powders for controlled long-term release.

Abstract: Apatite nuclei were synthesized by raising pH of simulated body fluid (SBF). Poly (lactic acid) (PLA) microspheres were soaked in apatite nuclei suspension, and then apatite nuclei were attached to surfaces of the PLA microspheres. When these PLA microspheres were soaked in SBF, apatite nuclei on the PLA microspheres induced HAp. As a result, PLA microspheres coated with HAp were fabricated. The HAp-coated PLA microspheres were soaked in acetone. The PLA core was dissolved out, and then consequently hollow microcapsules constructed of HAp were fabricated. As HAp microcapsules have properties of bioaffinity and non-toxicity, they were expected to be applicable to an excellent carrier of drug delivery system.

Abstract: Calcium phosphate (CaP) biomaterials containing Chinese medicine, Danshen (Salvia Miltiorrhiza Bunge, SMB), have been synthesized in our previous study via the wet chemical method. However, CaP biomaterials were generally synthesized in the alkaline solution. The purpose of the present study was to investigate the effect of pH on SMB and the influence of SMB on the synthesis of CaP biomaterials. The SMB solutions of different pH from 5.0 to 10.0, were scanned with the UV-VIS spectrophotometer (UV-VIS) in the wavelength ranged from 200.00 to 400.00 nm. CaP biomaterials containing SMB were synthesized from (NH4)2HPO4, Ca(NO3)2, NH4OH and SMB. The filtrates of the wet synthesis of CaP biomaterials containing SMB were measured by UV-VIS. The synthesized CaP biomaterials containing SMB were characterized by the X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The results showed that the maximum absorption peak appeared at 281.00 nm for solutions of pH 5.0, 6.0 and 7.0. Although there were a new absorption peaks as the pH were 8.0 and 9.0, the absorption curves of SMB became similar to that of SMB as pH at 7.0 after the pH were readjusted to 7.0. The absorption peak appeared an Einstein shift to 347.00 nm at pH 10.0, which did not return to 281.00 nm when the pH of SMB solution was readjusted to 7.0. The absorption peak of filtrates containing SMB of CaP biomaterials reaction system was still at 281.00 nm when their pH was 7.0 and 8.0. Moreover, SMB had no obvious effect on the phase component and functional groups of products. Hence, it could be predicted that calcium phosphate biomaterials containing SMB, such as DCPD and TCP containing SMB, which could be prepared at the pH ranged from 5.0 to 9.0.

Abstract: The time-dependent variation of the protein release from protein incorporated apatite cake in PBS solution was studied. When protein incorporated apatite cakes were immersed in PBS, the volume of cakes dropped for 1 day of soaking period and the shrinkage of specimen seems to be stabilized after 2 or 3 days soaking in PBS. The quantity of released protein from protein incorporated apatite cake was increased with an increase of soaking period. Around several % of protein came from the protein incorporated apatite cake in PBS for 2 weeks. The time-dependent protein release was relatively high for 1 day of soaking period, after that it slowly decreased. Compared to the decrease in volume of cake, the quantity ratio of released protein and total incorporated protein was less, which may be associated with recrystallization of the apatite hydrogel. FE-SEM observation revealed both crystals formed in air or under N2 atmosphere had similar rod like shape, and seems to be almost same in size. The change of surface appearance between 1 day and 4 days or longer soaking may be due to the dissolution of the surface layer and its recrystallization. The aggregate of apatite crystals formed in air is found to be compact, but some small cavities are observed in the specimens soaked in PBS for 4 – 11 days. The particle size of protein incorporated apatite were almost similar, independent on the soaking period. But the shape of apatite in aqueous solution is changing from square and angular shape to round shape.

Abstract: Bisphosphonates (BP) are drugs currently administered orally to treat diseases characterised by an excessive bone resorption. Alternative and more efficient delivery routes and more potent compounds are being investigated. Three implantable delivery systems, which allow the controlled release of therapeutic agents from the device core, are examined in this paper. (4- (aminomethyl) benzene) bisphosphonic acid (ABBP) was incorporated on Ca8.8Na0.8(PO4)4.8(CO3)1.2(OH)0.4F1.6 particles by refluxing the powder in a 60 mmol suspension in acetone at 60°C for 5 hours. 4-aminophenyl acetic bisphosphonate monosodium salt (APBP) and 1- H-indole-3-acetic bisphosphonate monosodium (IBP) were loaded on Ca10(PO4)6(OH)1F1 ceramic bodies by stirring the ceramic bodies in 0.04M BP solutions. Injectable acrylic cements based on self-curing formulations of methyl methacrylate (MMA) and vitamin E were loaded with APBP and IBP. The incorporation of ABBP was confirmed by MAS-NMR spectroscopy. Modified powder shows two different phosphorous environments, the first one at 2.91 ppm can be assigned to the apatite base and the second one at 18.0 ppm has to be attributed to the phosphonic group of the ABBP. The IBP addition on ceramic surfaces did not decrease the number of osteoclast colonies and appeared to improve the performance of the HA as a surface for osteoblast culture. A therapeutic dosage of APBP and IBP can be achieved from acrylic cements that showed lack of toxicity and an increased cellular activity and proliferation.

Abstract: Hydroxyapatite(HA) nanoparticles with hydrophobic surface have been synthesized using mono-alkyl phosphate (MAP) as modifier by hydrothermal synthesis method. The drug-loaded nano-HA/ Poly(ε-caprolactone)（PCL）composite microspheres and drug-load PCL microspheres were fabricated by an S/O/W emulsion solvent evaporation method. The microspheres morphology was investigated by scanning electron microscopy (SEM). Drug distribution in microsphere matrix was studied by confocal laser scanning microscope (CLSM). The results showed that the drug distributed evenly in the drug-HA-PCL microspheres, but only around the surface of the drug-PCL microspheres. The drug release profile showed that the nano-HA/PCL hybrid microspheres had low initial burst and could release continually for 90 days. This kind of hybrid microspheres can be used as a promising long-term drug delivery system in the bone.

Abstract: Hydroxyapatite (HAp)-alginate gels were developed as drug delivery carriers of the anti-cancer drug, water-insoluble paclitaxel (Taxol). The spray-drying technique was employed for loading the paclitaxel into spherical HAp microparticles with 1 to 20 μm in diameter. The microparticles loaded with 2.4 or 7.3wt% of paclitaxel were then mixed with sodium alginate, which was followed by Ca2+-mediated gelation. The compressive strength of the HAp-alginate gels and the release of paclitaxel from the gels in a medium were investigated in vitro. The alginate matrix was effective for the achievement of controlled release of anti-cancer drugs.

Abstract: Nanocomposites consisting of biologically active ions, which can enhance cell viability and activate gene expression, are regarded as promising bone regenerative materials. We report a new method for the layer-by-layer (LbL) assembly of biologically active strontium ions in the core-shell Silica@OCP system for an efficient controlled-release. The strontium ions were assembled by using a pH-responsive electrostatic interaction to generate three-dimensional gradients within the silica nanospheres, and then a porous OCP (octacalcium phosphate) shells was coated on the microunits tailored by polyelectrolyte molecules. This core-shell-like microstructure can achieve the multicomponents administration and controlled release of essential trace silicon and zinc ions based on the barrier effect of OCP shell and pH-dependent manner, respectively.

Abstract: Autologous bone chips are widely used in orthopedic surgery to fill large defects due to osteoinductive property but are limited in quantity. Several groups have reported the formation of mineralized bone after implantation of bioceramics in ectopic sites of different animals. However, osteoinduction by bioceramics has not yet proved to be equivalent to those of autologous bone. In this study, we compare the bone inducing capability of autologous bone chips and synthetic biphasic calcium phosphate (BCP) ceramics granules sintered at various temperatures. Both materials were implanted in muscles and femurs of goats inside hollow containers for 6, 12 and 24 weeks and analyzed by histology. This study showed that bone tissue formed in contact with micro porous ceramics sintered at low temperature as well as autologous bone chips both in ectopic and intrafemoral sites of goats.