Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin.

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.

A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone.

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres.

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

Fluorinated Organic Polymers for Cancer Drug Delivery.

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.

Biological Fixation of Bioactive Bone Cement in Vertebroplasty: The First Clinical Investigation of Borosilicate Glass (BSG) Reinforced PMMA Bone Cement.

PMMA bone cement has been clinically used for decades in vertebroplasty due to its high mechanical strength and satisfactory injectability. However, the interface between bone and PMMA is fragile and more prone to refracture in situ because PMMA lacks a proper biological response from the host bone with minimal bone integration and dense fibrous tissue formation. Here, we modified PMMA by incoporating borosilicate glass (BSG) with a dual glass network of [BO3] and [SiO4], which spontaneously modulates immunity and osteogenesis. In particular, the BSG modified PMMA bone cement (abbreviated as BSG/PMMA cement) provided an alkaline microenvironment that spontaneously balanced the activities between osteoclasts and osteoblasts. Furthermore, the trace elements released from the BSGs enhanced the osteogenesis to strengthen the interface between the host bone and the implant. This study shows the first clinical case after implantation of BSG/PMMA for three months using the dual-energy CT, which found apatite nucleation around PMMA instead of fibrous tissues, indicating the biological interface was formed. Therefore, BSG/PMMA is promising as a biomaterial in vertebroplasty, overcoming the drawback of PMMA by improving the biological response from the host bone.

Preparation and characterization of temperature-responsive magnetic composite particles for multi-modal cancer therapy.

The temperature-responsive magnetic composite particles were synthesized by emulsion-free polymerization of N-isopropylacrylamide (NIPAAm) and acrylamide (Am) in the presence of oleic acid-modified Fe(3)O(4) nanoparticles. The magnetic properties and heat generation ability of the composite particles were characterized. Furthermore, temperature and alternating magnetic field (AMF) triggered drug release behaviors of vitamin B(12)-loaded composite particles were also examined. It was found that composite particles enabled drug release to be controlled through temperature changes in the neighborhood of lower critical solution temperature. Continuous application of AMF resulted in an accelerated release of the loaded drug. On the other hand, intermittent AMF application to the composite particles resulted in an "on-off", stepwise release pattern. Longer release duration and larger overall release could be achieved by intermittent application of AMF as compared to continuous magnetic field. Such composite particles may be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release.

Spatial and Temporal Characteristics of Hand-Foot-and-Mouth Disease and Their Influencing Factors in Urumqi, China.

Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children. Urumqi is one of the most severely affected cities in northwestern China. This study aims to identify the spatiotemporal distribution characteristics of HFMD, and explore the relationships between driving factors and HFMD in Urumqi, Xinjiang. METHODS: HFMD surveillance data from 2014 to 2018 were obtained from the China Center for Disease Control and Prevention. The center of gravity and geographical detector model were used to analyze the spatiotemporal distribution characteristics of HFMD and identify the association between these characteristics and socioeconomic and meteorological factors. RESULTS: A total of 10,725 HFMD cases were reported in Urumqi during the study period. Spatially, the morbidity number of HFMD differed regionally and the density was higher in urban districts than in rural districts. Overall, the development of HFMD in Urumqi expanded toward the southeast. Temporally, we observed that the risk of HFMD peaked from June to July. Furthermore, socioeconomic and meteorological factors, including population density, road density, GDP, temperature and precipitation were significantly associated with the occurrence of HFMD. CONCLUSIONS: HFMD cases occurred in spatiotemporal clusters. Our findings showed strong associations between HFMD and socioeconomic and meteorological factors. We comprehensively considered the spatiotemporal distribution characteristics and influencing factors of HFMD, and proposed some intervention strategies that may assist in predicting the morbidity number of HFMD.

Bioactive borosilicate glass scaffolds: in vitro degradation and bioactivity behaviors.

Bioactive borosilicate glass scaffolds with the pores of several hundred micrometers and a competent compressive strength were prepared through replication method. The in vitro degradation and bioactivity behaviors of the scaffolds have been investigated by immersing the scaffolds statically in diluted phosphate solution at 37 degrees C, up to 360 h. To monitor the degradation progress of the scaffolds, the amount of leaching elements from the scaffolds were determined by ICP-AES. The XRD and SEM results reveal that, during the degradation of scaffolds, the borosilicate scaffolds converted to hydroxyapatite. The compressive strength of the scaffolds decreased during degradation, in the way that can be well predicted by the degradation products, or the leachates, from the scaffolds. MTT assay results demonstrate that the degradation products have little, if any, inhibition effect on the cell proliferation, when diluted to a certain concentration ([B] <2.690 and pH value at neutral level). The study shows that borosilicate glass scaffold could be a promising candidate for bone tissue engineering material.

Chemically and physically cross-linked polyvinyl alcohol-borosilicate gel hybrid scaffolds for bone regeneration.

The composite scaffolds of bioactive glasses and polymers are often used in bone regeneration which could improve the stiffness, compressive strength and bioactivity of polymers while maintaining the osteoconductivity and osteoinductivity of bioactive glasses. But due to complicated situations and limitations of compositing process, the prepared composite materials have low uniformity and obvious phase separation, leading to problems such as poor mechanical properties and inferior new bone formation capacity. In this paper, a modified sol-gel processing technique was used to realize the homogeneous inorganic-organic composites. After hydrolysis of the metal alkoxide, the sol was mixed with the aqueous solution of polyvinyl alcohol (PVA), and through gelation and chemical reaction, the mixture was solidified into the inorganic-organic composite hydrogel. The composites showed as a uniform single phase with interpenetrating networks of PVA gel and borosilicate gel (BG) that chemically and physically interacted at the scale of molecular or nanometer, therefore PVA-BG hybrids were obtained. When immersed in phosphate-buffered saline, the PVA-BG hybrid-derived scaffolds released beneficial ions into the medium and converted to hydroxyapatite. The scaffolds were not toxic to the rat bone marrow-derived mesenchymal stem cells (rBMSCs), and supported rBMSCs proliferation. Furthermore, the alkaline phosphatase activity of the rBMSCs and the expression levels of osteogenic-related genes (alkaline phosphatase, osteocalcin and runt-related transcription factor 2) increased significantly with increasing amount of BG in the hybrid scaffolds. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that PVA-BG hybrid scaffolds could enhance bone regeneration compared with PVA scaffolds. The results suggested that PVA-BG hybrid scaffolds may be a promising biomaterial for bone regeneration.

Stimulatory Effects of Boron Containing Bioactive Glass on Osteogenesis and Angiogenesis of Polycaprolactone: In Vitro Study.

Polycaprolactone (PCL) has attracted great attention for bone regeneration attributed to its cost-efficiency, high toughness, and good processability. However, the relatively low elastic modulus, hydrophobic nature, and insufficient bioactivity of pure PCL limited its wider application for bone regeneration. In the present study, the effects of the addition of boron containing bioactive glass (B-BG) materials on the mechanical properties and biological performance of PCL polymer were investigated with different B-BG contents (0, 10, 20, 30, and 40 wt.%), in order to evaluate the potential applications of B-BG/PCL composites for bone regeneration. The results showed that the B-BG/PCL composites possess better tensile strength, human neutral pH value, and fast degradation as compared to pure PCL polymers. Moreover, the incorporation of B-BG could enhance proliferation, osteogenic differentiation, and angiogenic factor expression for rat bone marrow stromal cells (rBMSCs) as compared to pure PCL polymers. Importantly, the B-BG also promoted the angiogenic differentiation for human umbilical vein endothelial cells (HUVECs). These enhanced effects had a concentration dependence of B-BG content, while 30 wt.% B-BG/PCL composites achieved the greatest stimulatory effect. Therefore the 30 wt.% B-BG/PCL composites have potential applications in bone reconstruction fields.

Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration.

It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks. This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were "switched off" when cultured in titrated material extracts with pH values higher than 7.8. To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast "switch on/off" behavior, the microenvironment boundary of the tested material was found to be 400 ± 50 µm, which is broader than the generally accepted value, 300 µm. Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone. To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.

Angiogenesis and Full-Thickness Wound Healing Efficiency of a Copper-Doped Borate Bioactive Glass/Poly(lactic- co-glycolic acid) Dressing Loaded with Vitamin E in Vivo and in Vitro.

There is an urgent demand for wound healing biomaterials because of the increasing frequency of traffic accidents, industrial contingencies, and natural disasters. Borate bioactive glass has potential applications in bone tissue engineering and wound healing; however, its uncontrolled release runs a high risk of rapid degradation and transient biotoxicity. In this study, a novel organic-inorganic dressing of copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) loaded with vitamin E (0-3.0 wt % vitamin E) was fabricated to evaluate its efficiency for angiogenesis in cells and full-thickness skin wounds healing in rodents. In vitro results showed the dressing was an ideal interface for the organic-inorganic mixture and a controlled release system for Cu2+ and vitamin E. Cell culture suggested the ionic dissolution product of the copper-doped and vitamin E-loaded dressing showed the best migration, tubule formation, and vascular endothelial growth factor (VEGF) secretion in human umbilical vein endothelial cells (HUVECs) and higher expression levels of angiogenesis-related genes in fibroblasts in vitro. Furthermore, this dressing also suggested a significant improvement in the epithelialization of wound closure and an obvious enhancement in vessel sprouting and collagen remodeling in vivo. These results indicate that the copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) dressing loaded with vitamin E is effective in stimulating angiogenesis and healing full-thickness skin defects and is a promising wound dressing in the reconstruction of full-thickness skin injury.

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml-1 to 2.5gml-1). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery.

Bioactive apatite incorporated alginate microspheres with sustained drug-delivery for bone regeneration application.

The strontium-substituted hydroxyapatite microspheres (SrHA) incorporated alginate composite microspheres (SrHA/Alginate) were prepared via adding SrHA/alginate suspension dropwise into calcium chloride solution, in which the gel beads were formed by means of crosslinking reaction. The structure, morphology and in vitro bioactivity of the composite microspheres were studied by using XRD, SEM and EDS methods. The biological behaviors were characterized and analyzed through inductively coupled plasma optical emission spectroscopy (ICP-OES), CCK-8, confocal laser microscope and ALP activity evaluations. The experimental results indicated that the synthetic SrHA/Alginate showed similar morphology to the well-known alginate microspheres (Alginate) and both of them possessed a great in vitro bioactivity. Compared with the control Alginate, the SrHA/Alginate enhanced MC3T3-E1 cell proliferation and ALP activity by releasing osteoinductive and osteogenic Sr ions. Furthermore, vancomycin was used as a model drug to investigate the drug release behaviors of the SrHA/Alginate, Alginate and SrHA. The results suggested that the SrHA/Alginate had a highest drug-loading efficiency and best controlled drug release properties. Additionally, the SrHA/Alginate was demonstrated to be pH-sensitive as well. The increase of the pH value in phosphate buffer solution (PBS) accelerated the vancomycin release. Accordingly, the multifunctional SrHA/Alginate can be applied in the field of bioactive drug carriers and bone filling materials.

In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing.

Full-thickness skin defects represent urgent clinical problem nowadays. Wound dressing materials are hotly needed to induce dermal reconstruction or to treat serious skin defects. In this study, the borate bioactive glass (BG) micro-fibers were fabricated and compared with the traditional material 45S5 Bioglass(®) (SiG) micro-fibers. The morphology, biodegradation and bioactivity of BG and SiG micro-fibers were investigated in vitro. The wound size reduction and angiogenic effects of BG and SiG micro-fibers were evaluated by the rat full-thickness skin defect model and Microfil technique in vivo. Results indicated that the BG micro-fibers showed thinner fiber diameter (1 µm) and better bioactivity than the SiG micro-fibers did. The ionic extracts of BG and SiG micro-fibers were not toxic to human umbilical vein endothelial cells (HUVECs). In vivo, the BG micro-fiber wound dressings obviously enhanced the formation of blood vessel, and resulted in a much faster wound size reduction than the SiG micro-fibers, or than the control groups, after 9 days application. The good skin defect reconstruction ability of BG micro-fibers contributed to the B element in the composition, which results in the better bioactivity and angiogenesis. As shown above, the novel bioactive borate glass micro-fibers are expected to provide a promising therapeutic alternative for dermal reconstruction or skin defect repair.

Effects of nano HAP on biological and structural properties of glass bone cement.

A novel type of glass-based nanoscale hydroxyapatite (HAP) bioactive bone cement (designed as GBNHAPC) was synthesized by adding nanoscale hydroxyapatite crystalline (20-40 nm), into the self-setting glass-based bone cement (GBC). The inhibition rate of nanoscale HAP and micron HAP on osteosarcoma U2-OS cells was examined. The effects of nanoscale HAP on the crystal phase, microstructure and compressive strength of GBNHAPC were studied, respectively. It was concluded that nanoscale HAP could inhibit the cell proliferation, whereas micron HAP could not, and that nanoscale HAP could be dispersed in the cement evenly and the morphology did not change significantly after a longer immersion time. XRD and FTIR results show nanoscale HAP did not affect the setting reaction of the cement. Furthermore, GBNHAPC had a higher compressive strength (92.6 +/- 3.8 MPa) than GBC (80.1 +/- 3.0 MPa). It was believed that GBNHAPC might be a desirable biomaterial that could not only fill bone defects but also inhibit cancer cell growth.

[Cytocompatibility of two porous bioactive glass-ceramic in vitro].

OBJECTIVE: To compare the cytocompatibility of two kinds porous bioactive glass-ceramic made by same raw materials. METHODS: Apatite/wollastonite bioactive glass-ceramic (4006) were prepared by sol-gel method, and bioactive glass (45S5) were prepared by melting method. Bone marrow stromal cells (BMSCs) were cultivated, differentiated and proliferated into osteoblasts, from a rabbit's marrow in the differentiatiofn culture medium with active function. The viability of BMSCs cultivated with extraction of these two kinds of biomaterial, which could represent the cytotoxicity effect of 4006 and 45S5 against BMSCs, was evaluated by the MTp assay. BMSCs were seeded and cocultivated with two kinds of biomaterial scaffolds respectively in vitro. The proliferation and biological properties of cells adhered to scaffolds were observed by inverted phase contrast microscope, scanning electron microscope (SEM), and environmental scanning electron microscope (ESEM), and a suitable cell amount for seeding on the scaffold was searched. RESULTS: There was no difference on the viability of BMSCs only cultured for one day by complete extract of 4006 and culture medium (P>0.05), but there was significant difference between them when the cells had been cultured for 3 days(P<0.01). The extract of 45S5 had significantly higher cytotoxicity than extract of culture medium (P<0.01). The BMSCs adhered, spread, and proliferated throughout the pores of the scaffold 4006, and the amount of cells adhered to 4006 was more than to 45S5. The adhered cells to 4006 increased with the rising amount of cells seeded. And 2 x 10(7) cells.mL-1 suspension resulted inthe highest cell adherence during the comparative cells adherence test. CONCLUSION: Apatite/woolastonite bioac tive glass-ceramic has good bioactivity and cytocompatibility. Therefore, it may have the potential to be a new cell vehicle for bone tissue engineering. And the suitable seeding cell amount of apatite/wollastonite bioactive glass-ceramic should be 2x10(7) cells.mL-1 or even more than that.

Mesoporous silica nanoparticles capped with disulfide-linked PEG gatekeepers for glutathione-mediated controlled release.

Hybrid mesoporous silica nanoparticles (MSNs), which were synthesized using the co-condensation method and engineered with unique redox-responsive gatekeepers, were developed for studying the glutathione-mediated controlled release. These hybrid nanoparticles constitute a mesoporous silica core that can accommodate the guests (i.e., drug, dye) and the PEG shell that can be connected with the core via disulfide-linker. Interestingly, the PEG shell can be selectively detached from the inner core at tumor-relevant glutathione (GSH) levels and facilitate the release of the encapsulated guests at a controlled manner. The structure of the resulting hybrid nanoparticles (MSNs-SS-mPEG) was comprehensively characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and nitrogen adsorption/desorption isotherms analysis. The disulfide-linked PEG chains anchored on MSNs could serve as efficient gatekeepers to control the on-off of the pores. Compared with no GSH, fluorescein dye as the model drug loaded into MSNs showed rapid release in 10 mM GSH, indicating the accelerated release after the opening of the pores regulated by GSH. Confocal microscopy images showed a clear evidence of the dye-loaded MSNs-SS-mPEG nanoparticles endocytosis into MCF-7 cells and releasing guest molecules from the pore inside cells. Moreover, in vitro cell viability test using MTT assay indicated that MSNs-SS-mPEG nanoparticles had no obvious cytotoxicity. These results indicate that MSNs-SS-mPEG nanoparticles can be used in the biomedical field.

Effects of strontium in modified biomaterials.

Strontium (Sr) plays a special role in bone remodelling, being associated with both the stimulation of bone formation and a reduction in bone resorption. Thus, the modification of biomaterials by partial or full substitution by Sr is expected to increase both bioactivity and biocompatibility. However, such effects have to be studied individually. Although no phase transition was found in Sr-substituted hydroxyapatite (Sr-HA), Sr-containing calcium silicate (Sr-CS) or Sr-containing borosilicate (Sr-BS), their biological performance was substantially affected by changes in the physico-chemical properties and Sr content of the materials. Three distinct outcomes were found for the presence of Sr: (1) increased HA solubility; (2) no significant effect on the degradation rate of CS; (3) apparent inhibition of the otherwise rapid degradation of BS. In each case the released Sr affected osteoblast proliferation and alkaline phosphatase activity, with clear evidence that an optimum Sr dose exists. Such chemical and biological variations must be disentangled for the behaviour to be properly understood and materials design to be advanced.

Bioactive borosilicate glass scaffolds: improvement on the strength of glass-based scaffolds for tissue engineering.

Three-dimensional macroporous scaffolds with the pore size of 200-500 mum were fabricated by replication method using bioactive borosilicate glass from Na(2)O-K(2)O-MgO-CaO-SiO(2)-P(2)O(5)-B(2)O(3) system. The effects of the strength of the strut in reticulated scaffold, as well as the geometrical parameter of the scaffold on the strength of reticulated scaffold were investigated. Scanning electron microscope (SEM) and X-ray diffraction (XRD) results show that the solidified glass struts in the reticulated scaffold could be obtained through a sufficient vicious flow of glass, during the fabrication. By increasing the solid content in slurries, from which the scaffold was made, the load-bearing units of the reticulated scaffold switch from struts to the walls between the pores, and the compressive strength dramatically climbs higher than the theoretical strength calculated by Gibson model. In particular, the compressive strength of the reticulated scaffold, as high as approximately 10 MPa with the porosity of approximately 70%, is close to the reported compressive values of human cancellous bone. This indicates the bioactive borosilicate glass-based scaffold is a promising candidate for bone tissue engineering.