Promising trends of bioceramics in the biomaterials field

Biomedical scientific community is currently demanding new advances in the designing of 3rd generation bioceramics, which promote bone tissue regeneration. In the last years, the development of supramolecular chemistry and the application of organic-inorganic hybrid materials in the biomedical field have resulted in a new generation of advanced bioceramics, which exhibit fascinating properties for regenerative purposes together with the possibility of being used as carriers of biologically active molecules. This communication overviews the evolution occurred from the first silica based bioceramics to the last advances in the synthesis of bioceramics for bone tissue regeneration. A critical review concerning the first bioactive glasses as well as the newest hybrid bioactive materials and templated mesoporous bioactive systems, will be performed from the point of view of their potential applications as replacement materials in bone repair and regeneration.     

Bioactive glasses as carriers for bioactive molecules and therapeutic drugs: a review

Bioactive glasses (BG) show great promise for bone tissue engineering based on their key properties, e.g., biocompatibility, biodegradability, osteoconductivity as well as osteogenic and angiogenic potential, which make them excellent candidates for bone tissue scaffolds and bone substitute materials. Recent work has shown that dissolution products of bioactive glasses have the potential to induce angiogenesis in addition to their known effect of influencing gene expression and promoting osteoblastic differentiation. One of the most interesting features of BG is their ability to bond both to soft and hard tissues, depending on their composition. To intensify the positive impact of BG for medical applications, there are considerable research efforts on using bioactive glass based platforms as carriers for the encapsulation, delivery and controlled release of bioactive molecules and therapeutic drugs. Different types of bioactive glasses have been considered in combination with different therapeutic drugs, hormones, growth factors and peptides. Using bioactive glasses as drug delivery system combines thus the effectiveness of therapeutic drugs (or bioactive/signaling molecules) with the intrinsic advantages of this inorganic biomaterial. Considering research carried out in the last 15?years, this review presents the different chemical compositions and morphologies of bioactive glasses used as carrier for bioactive molecules and therapeutic drugs and discusses the expanding potential of BG with drug delivery capability focusing in the field of bone tissue engineering.     

Tuning mesoporous silica dissolution in physiological environments: a review

Matrix degradation has a major impact on the release kinetics of drug delivery systems. Regarding ordered mesoporous silica materials for biomedical applications, their dissolution is an important parameter that should be taken into consideration. In this paper, we review the main factors that govern the mesoporous silica dissolution in physiological environments. We also provide the necessary knowledge to researchers in the area for tuning the dissolution rate of those matrices, so the degradation could be controlled and the material behaviour optimised.     

One‐step method for the preparation of poly(methyl methacrylate) modified titanium‐bioactive glass three‐dimensional scaffolds for bone tissue engineering

A novel three‐dimensional (3D) titanium (Ti)‐doping meso‐macroporous bioactive glasses (BGs)/poly(methyl methacrylate) (PMMA) composite was synthesised using PMMA and EO₂₀ PO₇₀ EO₂₀ (P₁₂₃) as the macroporous and mesoporous templates, respectively. Unlike the usual calcination method, the acid steam technique was used to improve the polycondensation of Ti‐BGs, and then PMMA was partially extracted via chloroform to induce the macroporous structure. Simultaneously, the residual PMMA which remained in the wall enhanced the compressive strength to 2.4 MPa (0.3 MPa for pure BGs). It is a simple and green method to prepare the macro‐mesoporous Ti‐BGs/PMMA. The materials showed the 3D interconnected hierarchical structure (250 and 3.4 nm), making the fast inducing‐hydroxyapatite growth and the controlled drug release. Besides mentioned above, the good antimicrobial property and biocompatible of the scaffold also ensure it is further of clinical use. Herein, the fabricated materials are expected to have potential application on bone tissue regeneration.Inspec keywords: titanium, bone, tissue engineering, glass, materials preparation, biomedical materials, polymers, porous materials, drug delivery systems, nanomedicineOther keywords: poly(methyl methacrylate), PMMA preparation, 3D titanium‐bioactive glass scaffold, bone tissue engineering, titanium‐doping mesomacroporous bioactive glass, bioactive glass‐PMMA composite, macroporous template, mesoporous template, calcination method, acid steam technique, titanium‐bioactive glass polycondensation, macroporous structure, green method, macromesoporous titanium‐bioactive glass‐PMMA, 3D interconnected hierarchical structure, fast inducing‐hydroxyapatite growth, controlled drug release, bone tissue regeneration, Ti     

Mesoporous hydroxyapatite by hard templating of silica and carbon foams for protein release

Calcium phosphates, particularly hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ (HA), are widely used for bone regeneration due to their biocompatibility and good resorption properties. However, their performance upon implantation is improved when they are associated with bioactive molecules such as growth factors. Using mesoporous HA leads to improved protein adsorption and release kinetics because the diameter of the mesopores (2–50 nm) is in the same range as their size. We prepared this type of material by the nanocasting method using three different templates: a silica foam and two carbon templates derived from it using propylene or sucrose as carbon source. We investigated the influence of the template, the calcination temperature and of the conditions during template removal. We obtained HA materials with a surface area of up to 90 m² g^?1 and with an intergranular mesopore volume of up to 0.4 cm³ g^?1. In this paper, we show for the first time that the synthesis of mesoporous HA from a mesoporous silica foam template allows eliminating the template at lower temperatures (in an alkaline medium), thus preventing the sintering of the HA. These materials have interesting properties for drug delivery applications. The protein adsorption and release capacities of these HAs were tested with two model proteins, bovine serum albumin (BSA), and Cytochrome C. These materials are an important milestone for future bone regeneration systems based on HA associated with human growth factor proteins.     

Bioceramics: from bone regeneration to cancer nanomedicine

Research on biomaterials has been growing in the last few years due to the clinical needs in organs and tissues replacement and regeneration. In addition, cancer nanomedicine has recently appeared as an effective means to combine nanotechnology developments towards a clinical application. Ceramic materials are suitable candidates to be used in the manufacturing of bone-like scaffolds. Bioceramic materials may also be designed to deliver biologically active substances aimed at repairing, maintaining, restoring or improving the function of organs and tissues in the organism. Several materials such as calcium phosphates, glasses and glass ceramics able to load and subsequently release in a controlled fashion drugs, hormones, growth factors, peptides or nucleic acids have been developed. In particular, to prevent post surgical infections bioceramics may be surface modified and loaded with certain antibiotics, thus preventing the formation of bacterial biofilms. Remarkably, mesoporous bioactive glasses have shown excellent characteristics as drug carrying bone regeneration materials. These bioceramics are not only osteoconductive and osteoproductive, but also osteoinductive, and have therefore been proposed as ideal components for the fabrication of scaffolds for bone tissue engineering. A recent promising development of bioceramic materials is related to the design of magnetic mediators against tumors. Magnetic composites are suitable thermoseeds for cancer treatment by hyperthermia. Moreover, magnetic nanomaterials offer a wide range of possibilities for diagnosis and therapy. These nanoparticles may be conjugated with therapeutic agents and heat the surrounding tissue under the action of alternating magnetic fields, enabling hyperthermia of cancer as an effective adjunct to chemotherapy regimens.     

An in situ synthesis of mesoporous SBA-16/hydroxyapatite for ciprofloxacin release: in vitro stability and cytocompatibility studies

The present work developed a biomaterial (HA/SBA-16) based on the growth of calcium phosphate (HA) particles within an organized silica structure (SBA-16) to evaluate its application as a drug delivery system. The samples were charged with ciprofloxacin as a model drug and in vitro release assays were carried out. The samples were characterized by elemental analysis (CHN), Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray scattering (SAXS) and X-ray diffraction. The results obtained by TEM, SEM and SAXS reveal a well-defined cubic arrangement of a uniform spherical mesoporous structure, an intrinsic characteristic of these materials, which indicated that SBA-16 and HA/SBA-16 could potentially encapsulate bioactive molecules by means of ordered mesopores. It was found that both surface interaction and pore volume affect the rate and amount of ciprofloxacin released from the mesoporous materials. In vitro assays were performed to evaluate the adhesion, viability, and growth behavior of human adipose tissue-derived stem cells (hADSC) on SBA-16 and HA/SBA-16 nanocomposites to verify their potential as a scaffold for application in bone–tissue engineering using MTT assay and alkaline phosphatase activity tests. The results showed that the materials are promising systems for bone repair, providing a good environment for the adhesion and proliferation of rat mesenchymal stem cells and hADSC in vitro.     

SBA-15 ordered mesoporous silica inside a bioactive glass–ceramic scaffold for local drug delivery

The paper reports the synthesis of an ordered silica mesostructure of the SBA-15 type inside a macroporous bioactive glass-ceramic scaffold of the type SiO(2)-CaO-K(2)O, to combine the bioactivity of the latter with the release properties of the former, in view of local drug delivery from implants designed for tissue engineering. The standard procedure for SBA-15 synthesis has been modified to minimize the damage to the scaffold caused by the acidic synthesis medium. The composite system has been characterized by means of Scanning Electron Microscopy (coupled with EDS analysis), Small Angle X-Ray Diffraction, Thermogravimetry analysis and Infrared Spectroscopy: the formation of a well ordered hexagonal mesostructure was confirmed. Ibuprofen has been chosen as model drug. The uploading properties have been investigated of the scaffold-mesoporous silica composite as compared with the scaffold as such, and a five-fold increase in the adsorbing properties toward ibuprofen was found, due to the presence of the ordered mesoporous silica. The ibuprofen release to a SBF solution in vitro is complete in 1 day. Retention of bioactivity from the glass-ceramic scaffold after the silica mesostructure incorporation has been observed.     

Recent Advances of Using Hybrid Nanocarriers in Remotely Controlled Therapeutic Delivery

The development of hybrid biomaterials has been attracting great attention in the design of materials for biomedicine. The nanosized level of inorganic and organic or even bioactive components can be combined into a single material by this approach, which has created entirely new advanced compositions with truly unique properties for drug delivery. The recent advances in using hybrid nanovehicles as remotely controlled therapeutic delivery carriers are summarized with respect to different nanostructures, including hybrid host–guest nanoconjugates, micelles, nanogels, core–shell nanoparticles, liposomes, mesoporous silica, and hollow nanoconstructions. In addition, the controlled release of guest molecules from these hybrid nanovehicles in response to various remote stimuli such as alternating magnetic field, near infrared, or ultrasound triggers is further summarized to introduce the different mechanisms of remotely triggered release behavior. Through proper chemical functionalization, the hybrid nanovehicle system can be further endowed with many new properties toward specific biomedical applications.     

Mesoporous Silica Nanoparticles for Intracellular Controlled Drug Delivery

The application of nanotechnology in the field of drug delivery has attracted much attention in the latest decades. Recent breakthroughs on the morphology control and surface functionalization of inorganic‐based delivery vehicles, such as mesoporous silica nanoparticles (MSNs), have brought new possibilities to this burgeoning area of research. The ability to functionalize the surface of mesoporous‐silica‐based nanocarriers with stimuli‐responsive groups, nanoparticles, polymers, and proteins that work as caps and gatekeepers for controlled release of various cargos is just one of the exciting results reported in the literature that highlights MSNs as a promising platform for various biotechnological and biomedical applications. This review focuses on the most recent progresses in the application of MSNs for intracellular drug delivery. The latest research on the pathways of entry into live mammalian and plant cells together with intracellular trafficking are described. One of the main areas of interest in this field is the development of site‐specific drug delivery vehicles; the contribution of MSNs toward this topic is also summarized. In addition, the current research progress on the biocompatibility of this material in vitro and in vivo is discussed. Finally, the latest breakthroughs for intracellular controlled drug release using stimuli‐responsive mesoporous‐silica‐based systems are described.     

药物在有序介孔氧化硅纳米孔道中组装与控缓释研究进展

有序介孔纳米氧化硅材料是一种越来越受到重视的新型药物控缓释栽体材料.综述了其与作为药物控缓释载体用途相关的控制性合成的进展以及其纳米孔道结构特性对纳米孔道中药物分子组装、控缓释行为的影响,为控缓释药物研究人员研究药物分子的控缓释行为和药物分子组装技术及开发新型药物分子载体材料提供研究依据.     

Synthesis and characterization of mesoporous silica/poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) functional hybrid useful for drug delivery

Recent studies indicate the use of mesoporous silica and polymeric sensitive hydrogels as suitable for drug delivery systems due to their specific characteristics. Polymeric hydrogels, such as poly(N-isopropylacrylamide) [P(N-iPAAm)], show volumetric expansion/contraction behaviour at 306 K, which that can be used to develop a thermosensitive drug delivery system. In this study, we report a facile and direct synthesis route to obtain hybrid functional nanosystems based on silica-P(N-iPAAm) by using a neutral surfactant and without any functionalization method and the assessment of its release rate of a model drug. The materials were characterized by Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy, transmission electron microscopy and thermal analysis. A release assay with atenolol monitored by UV–Vis spectroscopy was performed for pure SBA-15 and a hybrid system at different temperatures in order to evaluate the influence of the thermosensitive behaviour of the polymer on the release kinetics. The response of the hybrid system as a drug delivery device is influenced by the volumetric contraction of P(N-iPAAm) up to the lower critical solution temperature (LCST) due to phase transition. Above the LCST, drug release depends essentially on the temperature.     

Macroporous/mesoporous bioglasses doped with Ag/TiO(2) for dual drug action property and bone repair

A series of macroporous-mesoporous bioglasses (MMBGs) doped with Ag, TiO(2) and Ag/TiO(2) have been successfully prepared using the nature plants as the macroporous templates and P123 as the mesoporous one. The dual drug action (antifungus and anti-inflammatory) and bone regeneration systems have been obtained by Ibuprofen (Ibu) loaded. Meanwhile, the antifungus as well as drug control release profiles of these materials have been investigated. Compared with pure MMBGs, MMBGs-Ag, MMBGs-TiO(2) and MMBGs-Ag/TiO(2) showed much higher antimicrobial efficiency, faster hydroxyapatite-forming ability and better drug sustained release performance. The multifunctional hierarchical porous bioglasses materials may have potential applications in bone tissue engineering.     

Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: opportunities and challenges

Porous silica-based drug delivery systems have shown considerable promise for improving the oral delivery of poorly water-soluble drugs. More specifically, micro- and meso-porous silica carriers have high surface areas with associated ability to physically adsorb high-drug loads in a molecular or amorphous form; this allows molecular state drug release in aqueous gastrointestinal environments, potential for supersaturation, and hence facilitates enhanced absorption and increased bioavailability. This review focuses primarily on the ability of porous silica materials to modulate in vitro drug release and enhance in vivo biopharmaceutical performance. The key considerations identified and addressed are the physicochemical properties of the porous silica materials (e.g. the particle and pore size, shape, and surface chemistry), drug specific properties (e.g. pKa, solubility, and nature of interactions with the silica carrier), potential for both immediate and controlled release, drug release mechanisms, potential for surface functionalization and inclusion of precipitation inhibitors, and importance of utilizing relevant and effective in vitro dissolution methods with discriminating dissolution media that provides guidance for in vivo outcomes (i.e. IVIVC).     

One-pot synthesis of magnetic,macro/mesoporous bioactive glasses for bone tissue engineering

Abstract

Magnetic and macro/mesoporous bioactive glasses were synthesized by a one-pot method via a handy salt leaching technique. It was identified to be an effective and simple synthetic strategy. The non-ionic triblock copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123), was used as the structure directing agent for mesoporous structure but also as the reductant to reduce the iron source into magnetic iron oxide. The prepared materials exhibited excellent super-paramagnetic property with interconnected macroporous (200–300 μm) and mesoporous (3.4 nm) structure. Furthermore, their outstanding drug storage/release properties and rapid (5) induction of hydroxyapatite growth ability were investigated after immersing in simulated body fluid solution at 37 °C. Notably, the biocompatibility assessment confirmed that the materials obtained presented good biocompatibility and enhanced adherence of HeLa cells. Herein, the novel materials are expected to have potential application for bone tissue engineering.     

Bioactive glass nanotube scaffold with well-ordered mesoporous structure for improved bioactivity and controlled drug delivery

In this study, a novel mesoporous bioactive glass nanotube (MBGN) scaffold has been fabricated via template-assisted sol-gel method using bacterial cellulose (BC) as template and nonionic block copolymer (P123) as pore-directing agent. The scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, and N₂ adsorption-desorption analysis. Furthermore, simvastatin was used to evaluate the loading efficiency and release kinetics of the scaffold. The obtained scaffold displays nanofiber-like morphology, ordered mesopores on the tube walls, and interconnected three-dimensional (3D) network structure that completely replicates the BC template. In addition, it shows dual pore sizes (16.2 and 3.3 nm), large specific surface area (537.2 m² g⁻¹) and pore volume (1.429 cm³ g⁻¹). More importantly, the scaffold possesses excellent apatite-forming ability and sustainable drug release as compared to the counterpart scaffold without mesopores. This unique scaffold can be considered a promising candidate for drug delivery and bone tissue regeneration.     

Mesoporous Silica Nanoparticles: Synthesis,Biocompatibility and Drug Delivery

In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle‐type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano‐based targeted cancer therapy and MSN‐based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.     

The properties of biomimetically processed calcium phosphate on bioactive ceramics and their response on bone cells

This study looks for grounds to alter the chemical composition (phosphate, calcium, silica and carbonate), dissolution properties, structure and nanotopography of the biomimetically processed surfaces on bioactive ceramics to optimize their shown ability to influence bone cell behaviour and production of new bone. In the bone environment desirable characteristic of these materials is their ability to be remodeled by natural osteoclastic resorption. Different silica and carbonate containing calcium phosphate layers were prepared on bioactive glasses 9 (S53P4) and 1-98 (S53P2) and sol-gel processed pure silica SiO₂ in C- and R-SBF (conventional and revised simulated body fluid) for varying periods of time. It was shown that in R-SBF the CaP layer formed faster compared to C-SBF. The CaP layer in the R-SBF contained more carbonate (CO₃ ²⁻) compared to that formed with the same immersion time in C-SBF. The CaP so formed in R-SBF with faster precipitation is more amorphous than the bonelike HCA formed in C-SBF. The results indicate that the most suitable surface for both osteoblasts and osteoclasts was found to be an amorphous CaP having mesoporous nanotopography and proper dissolution rate of calcium and silica.     

聚焦超声控制交联聚(甲基丙烯酸甲酯-丙烯酸丁酯)/介孔二氧化硅复合材料的形状记忆和药物释放

研究了交联聚(甲基丙烯酸甲酯-丙烯酸丁酯)/介孔二氧化硅复合材料在聚焦超声作用下的形状记忆性能和药物控制释放行为。实验表明,介孔二氧化硅的添加对复合材料声-热转换效率有一定提高作用,从而可以提高其形状回复率。另一方面,药物释放实验证实了此复合材料具有良好的聚焦超声控制药物释放性能,在多次聚焦超声ON/OFF转换下,药物呈现明显ON/OFF释放状态的转换,并且随着超声强度和聚合物基体中药物含量的增大,释放速率显著提高。与直接添加纯布洛芬相比,介孔二氧化硅的引入可以显著降低药物预释放量,提高释放可控性。     

Engineering nanospaces: ordered mesoporous silicas as model substrates for building complex hybrid materials

This contribution summarizes investigations of organic-inorganic hybrid materials wherein the inorganic phase is ordered mesoporous silica such as MCM-41 and SBA-15. The review, which covers work performed in the last three years, emphasizes studies of: (1) covalently attached functional groups, (2) new approaches to functionalization, (3) approaches for achieving high densities of uniform functional groups, (4) periodic mesoporous organosilicas (PMOs) with hierarchical ordering, (5) new functional chemistries, and (6) the application of new materials to enantioselective catalysis and emerging areas. The review concludes with the authors outlining some outstanding problems in the field.