Tb-Doped core-shell-shell nanophosphors for enhanced X-ray induced luminescence and sensitization of radiodynamic therapy.

The development of radiation responsive materials, such as nanoscintillators, enables a variety of exciting new theranostic applications. In particular, the ability of nanophosphors to serve as molecular imaging agents in novel modalities, such as X-ray luminescence computed tomography (XLCT), has gained significant interest recently. Here, we present a radioluminescent nanoplatform consisting of Tb-doped nanophosphors with an unique core/shell/shell (CSS) architecture for improved optical emission under X-ray excitation. Owing to the spatial confinement and separation of luminescent activators, these CSS nanophosphors exhibited bright optical luminescence upon irradiation. In addition to standard physiochemical characterization, these CSS nanophosphors were evaluated for their ability to serve as energy mediators in X-ray stimulated photodynamic therapy, also known as radiodynamic therapy (RDT), through attachment of a photosensitizer, rose bengal (RB). Furthermore, cRGD peptide was used as a model targeting agent against U87 MG glioblastoma cells. In vitro RDT efficacy studies suggested the RGD-CSS-RB in combination with X-ray irradiation could induce enhanced DNA damage and increased cell killing, while the nanoparticles alone are well tolerated. These studies support the utility of CSS nanophosphors and warrants their further development for theranostic applications.

Microwave processing of calcium phosphate and magnesium phosphate based orthopedic bioceramics: A state-of-the-art review.

The main theme of this paper is to review microwave-assisted synthesis and processing of calcium and magnesium phosphate bioceramics. Microwave processing of advanced materials has been an active field of research for the last three decades and has been already reviewed in the literature. Microwave processing of bioceramics is being pursued for almost the same period of time. Unfortunately, to the best of our knowledge, we are not aware of any comprehensive review in the literature. Our group has been a significant contributor to the field, and we feel that it is an appropriate time for reviewing the state-of-the-art of the field. The paper is divided into several sections. After rationalizing the motivation behind writing this paper in the introduction, the second section builds on some fundamental aspects of microwave-matter interactions. The third section, representing the synthesis aspects, is subdivided into five sub-sections focusing on various calcium and magnesium phosphates in both crystalline and amorphous forms. The fourth section focuses on magnesium phosphate-based bioceramics. The fifth and the sixth section describe results on the utility of microwave assistance in developing multi-functional coatings on medical implants and orthopedic cements respectively. The subsequent section reviews results on microwave sintering of calcium and magnesium phosphates. The paper concludes with remarks on unresolved issues and future directions of research. It is expected that this comprehensive review on the interdisciplinary topic will further propel the exploration of other novel applications of microwave technology in processing biomaterials by a diverse group of scientists and engineers. STATEMENT OF SIGNIFICANCE: 1. This review highlights the broad-spectrum capabilities of microwave applications in processing orthopedic bioceramics. 2. The article covers "processing" in the broadest sense of the word, comprising of material synthesis, sintering, coating formation, and setting of orthopedic cements. It also expands beyond conventional calcium phosphates to include the emergent family of magnesium phosphates. 3. In vitro/in vivo responses of microwave-processed bioceramics are discussed thus providing an integral understanding of biological aspects of these materials. 4. The comprehensive review on this interdisciplinary topic will help researchers in various disciplines to appreciate the significance and usefulness of microwaves in biomaterials processing. Further, we also believe that it will propel the exploration of other novel applications of microwave technology in the biomaterials sector.

Microwave assisted coating of bioactive amorphous magnesium phosphate (AMP) on polyetheretherketone (PEEK).

Polyetheretherketone (PEEK) with great thermal and chemical stability, desirable mechanical properties and promising biocompatibility is being widely used as orthopedic and dental implant materials. However, the bioinert surface of PEEK can hinder direct osseointegration between the host tissue and PEEK based implants. The important signatures of this paper are as follows. First, we report for the formation of osseointegrable amorphous magnesium phosphate (AMP) coating on PEEK surface using microwave energy. Second, coatings consist of nano-sized AMP particles with a stacked thickness of 800nm. Third, coatings enhance bioactivity in-vitro and induce significantly high amount of bone-like apatite coating, when soaked in simulated body fluid (SBF). Fourth, the as-deposited AMP coatings present no cytotoxicity effects and are beneficial for cell adhesion at early stage. Finally, the high levels of expression of osteocalcin (OCN) in cells cultured on AMP coated PEEK samples indicate that AMP coatings can promote new bone formation and hence osseointegration.

Microwave-assisted magnesium phosphate coating on the AZ31 magnesium alloy.

Due to the combination of many unique properties, magnesium alloys have been widely recognized as suitable metallic materials for fabricating degradable biomedical implants. However, the extremely high degradation kinetics of magnesium alloys in the physiological environment have hindered their clinical applications. This paper reports for the first time the use of a novel microwave-assisted coating process to deposit magnesium phosphate (MgP) coatings on the Mg alloy AZ31 and improve its in vitro corrosion resistance. Newberyite and trimagnesium phosphate hydrate (TMP) layers with distinct features were fabricated at various processing times and temperatures. Subsequently, the corrosion resistance, degradation behavior, bioactivity and cytocompatibility of the MgP coated AZ31 samples were investigated. The potentiodynamic polarization tests reveal that the corrosion current density of the AZ31 magnesium alloy in simulated body fluid (SBF) is significantly suppressed by the deposited MgP coatings. Additionally, it is seen that MgP coatings remarkably reduced the mass loss of the AZ31 alloy after immersion in SBF for two weeks and promoted precipitation of apatite particles. The high viability of preosteoblast cells cultured with extracts of coated samples indicates that the MgP coatings can improve the cytocompatibility of the AZ31 alloy. These attractive results suggest that MgP coatings, serving as the protective and bioactive layer, can enhance the corrosion resistance and biological response of magnesium alloys.

Magnesium substitution in the structure of orthopedic nanoparticles: A comparison between amorphous magnesium phosphates, calcium magnesium phosphates, and hydroxyapatites.

As biocompatible materials, magnesium phosphates have received a lot of attention for orthopedic applications. During the last decade multiple studies have shown advantages for magnesium phosphate such as lack of cytotoxicity, biocompatibility, strong mechanical properties, and high biodegradability. The present study investigates the role of Mg(+2) and Ca(+2) ions in the structure of magnesium phosphate and calcium phosphate nanoparticles. To directly compare the effect of Mg(+2) and Ca(+2) ions on structure of nanoparticles and their biological behavior, three groups of nanoparticles including amorphous magnesium phosphates (AMPs) which release Mg(+2), calcium magnesium phosphates (CMPs) which release Mg(+2) and Ca(+2), and hydroxyapatites (HAs) which release Ca(+2) were studied. SEM, TEM, XRD, and FTIR were used to evaluate the morphology, crystallinity, and chemical properties of the particles. AMP particles were homogeneous nanospheres, whereas CMPs were combinations of heterogeneous nanorods and nanospheres, and HAs which contained heterogeneous nanosphere particles. Cell compatibility was monitored in all groups to determine the cytotoxicity effect of particles on studied MC3T3-E1 preosteoblasts. AMPs showed significantly higher attachment rate than the HAs after 1 day and both AMPs and CMPs showed significantly higher proliferation rate when compared to HAs after 7days. Gene expression level of osteoblastic markers ALP, COL I, OCN, OPN, RUNX2 were monitored and they were normalized to GAPDH housekeeping gene. Beta actin expression level was monitored as the second housekeeping gene to confirm the accuracy of results. In general, AMPs and CMPs showed higher expression level of osteoblastic genes after 7 days which can further confirm the stimulating role of Mg(+2) and Ca(+2) ions in increasing the proliferation rate, differentiation, and mineralization of MC3T3-E1 preosteoblasts.

Rapid coating of AZ31 magnesium alloy with calcium deficient hydroxyapatite using microwave energy.

Due to their unique biodegradability, magnesium alloys have been recognized as suitable metallic implant materials for degradable bone implants and bioresorbable cardiovascular stents. However, the extremely high degradation rate of magnesium alloys in physiological environment has restricted its practical application. This paper reports the use of a novel microwave assisted coating technology to improve the in vitro corrosion resistance and biocompatibility of Mg alloy AZ31. Results indicate that a dense calcium deficient hydroxyapatite (CDHA) layer was uniformly coated on a AZ31 substrate in less than 10min. Weight loss measurement and SEM were used to evaluate corrosion behaviors in vitro of coated samples and of non-coated samples. It was seen that CDHA coatings remarkably reduced the mass loss of AZ31 alloy after 7days of immersion in SBF. In addition, the prompt precipitation of bone-like apatite layer on the sample surface during immersion demonstrated a good bioactivity of the CDHA coatings. Proliferation of osteoblast cells was promoted in 5days of incubation, which indicated that the CDHA coatings could improve the cytocompatibility of the AZ31 alloy. All the results suggest that the CDHA coatings, serving as a protective layer, can enhance the corrosion resistance and biological response of magnesium alloys. Furthermore, this microwave assisted coating technology could be a promising method for rapid surface modification of biomedical materials.