Biodegradable and Bioactive Porous Polymer/Inorganic Nanocomposites Scaffolds for Biomedical Applications

With the aging of populations and prolonged life expectancy, there is an increasing demand for bone grafts or synthetic materials that can potentially replace, repair or regenerate lost, injured or diseased bone. Tissue engineering (TE) is one of the approaches being investigated to tackle this problem. In common TE strategies, a three-dimensional structure, termed “scaffold”, fabricated from a suitable artificial or natural material. In bone tissue engineering, a scaffolding material is used either to induce formation of bone from the surrounding tissue or to act as a carrier or template for implanted bone cells or other agents. To serve as a scaffold, the material must be biocompatible, osteoconductive, and osteointegrative, and have enough mechanical strength to provide structural support during the bone growth and remodeling. Several attempts have been successfully made to construct porous scaffolds with desired porosity and appropriate mechanical performance from inorganic materials such as bioactive ceramics and glasses, from biodegradable polymers and their composites. The focus of biomaterial design for tissue engineering applications has recently been directed towards bioactive components that facilitate biomaterial integration and native tissue regeneration at the implant site. During the last four decades, various materials known as ‘bioactive materials’ such as glasses, sintered hydroxyapatite, glass ceramics, composite materials, etc., have been synthesized and developed for medical applications. A significant characteristic of bioactive materials is their ability to bond with living bone through the formation of a hydroxyapatite (HA) interface layer. A recognized method to estimate the bone-bonding potential ability of material is simulated body fluid method (SBF), which involves immersing materials into SBF for bone-like apatite formation on its surface according to Kokubo et al. In other words, the behavior in vivo could be predicted by using SBF method in vitro. One remarkable success of bioactive ceramics as implant materials is the clinical use of sintered hydroxyapatite (HA) due to its bioactivity and osteoconductivity. However, the low fracture toughness of HA ceramic limits the scope of clinical applications. In recent years, more attentions have been focused on developing novel bioactive ceramics with improved properties. More recently, extensive interests have been shown in developing new bioactive inorganic materials containing CaO–SiO2 component for biomedical applications. Calcium silicate-based ceramics have received great attention as materials for bone tissue regeneration due to their excellent bioactivity. Compared to phosphate-based bioceramics, silicate bioceramics possess a wide range of chemical compositions and crystal structures, which contribute to their adjustable physicochemical properties, such as mechanical strength, bioactivity and degradation, providing them with suitable characteristics to be used as biomaterials. However, a major drawback of the CaSiO3 ceramics is their high dissolution rate, leading to a high pH value in the surrounding environment, which is detrimental to cells, which can be modified by incorporation of different elements such as Zn, Mg, Sr, Ti and Zr. In any case, the proposed approach can be extended to those more complex bioceramic compositions. In particular, due to the difficulties with sintering, silicate ceramics are generally obtained by complex techniques, such as the hydrothermal method, devitrification of glass, sol–gel processing, spark plasma-sintering, solution combustion processes etc. The sol–gel method is well suited for the preparation of complex ternary and quaternary silicate ceramics, as it allows for a precise control of the stoichiometry of the starting materials. However, it is of difficult industrialization, in the case of the fabrication of bulk components, because of the cost of the raw materials, the presence of large amounts of solvents and the associated drying problems. The current project is aiming at developing and fabricating of bioactive silicate-based ceramics from preceramic polymers (commercially available polymethylsiloxanes, silicones), and fillers (commercially available MgO, CaO, ZnO, TiO2, nano- and/or micro-particles), in the form of tablets, foams and 3D printed structures using additive manufacturing technology, to be used as bioactive scaffolds and biomaterials, thereby confirming that the proposed approach can be used to obtain components suitable for bone tissue regeneration. The incorporation of fillers, that generally can be passive or active, into the preceramic system is considered one of the most effective strategies to produce the silicate ceramics with different composition and structures as well as, to decrease the shrinkage and the formation of macro-defects in the produced ceramics. The approach of adding different oxide precursors (such as CaO and/or CaO, MgO and TiO2) as fillers enabled developing of different silicate bioactive ceramics (such as wollastonite (CaSiO3), hardystonite (Ca2ZnSi2O7), diopside (CaMgSi2O6) and sphene (CaTiSiO5)) as a result of the reactions between the preceramic polymers and these reactive fillers, occurring during the ceramization process and leading to the formation of specific crystalline phases with highly phase assemblage, that are known to be difficulty achievable by the conventional synthesis methods. A particular attention will be given to the production of open-celled porous components, to be employed as scaffolds for bone tissue engineering. These components will be prepared by various techniques, including unconventional direct foaming of silicone mixtures and additive manufacturing technology. Once the ceramic materials and scaffolds will be prepared, they will be fully characterized in terms of crystalline phase assemblage, physical and mechanical properties as well as microstructure analysis. The remarkable bioactivity of these scaffolds will be the main object of current investigations

Bioactive glass-ceramic scaffolds from novel 'inorganic gel casting' and sinter-crystallization

Highly porous wollastonite-diopside glass-ceramics have been successfully obtained by a new gel-casting technique. The gelation of an aqueous slurry of glass powders was not achieved according to the polymerization of an organic monomer, but as the result of alkali activation. The alkali activation of a Ca-Mg silicate glass (with a composition close to 50 mol % wollastonite50 mol % diopside, with minor amounts of Na2O and P2O5) allowed for the obtainment of well-dispersed concentrated suspensions, undergoing progressive hardening by curing at low temperature (40 degrees C), owing to the formation of a C-S-H (calcium silicate hydrate) gel. An extensive direct foaming was achieved by vigorous mechanical stirring of partially gelified suspensions, comprising also a surfactant. The open-celled structure resulting from mechanical foaming could be frozen' by the subsequent sintering treatment, at 900-1000 degrees C, causing substantial crystallization. A total porosity exceeding 80%, comprising both well-interconnected macro-pores and micro-pores on cell walls, was accompanied by an excellent compressive strength, even above 5 MPa

Masked stereolithography of wollastonite-diopside glass-ceramics from novel silicone-based liquid feedstock

Silicate bioceramics, including systems based on the simultaneous presence of wollastonite (CaSiO3) and diopside (CaMgSi2O6), are of great interest in bone tissue engineering applications, especially in form of variously shaped three-dimensional scaffolds, as determined by application of several additive manufacturing technologies. In this framework, silicone resins, properly modified with CaO- and MgO-based fillers and blended with photocurable acrylates, are attractive both as precursors and as feedstock for additive manufacturing technologies, including stereolithography. The use of powder fillers, however, may lead to issues with homogeneity or with printing resolution (owing to light scattering). The present paper aims at presenting the first results from a new concept of incorporation of CaO and MgO, relying on salts dispersed in emulsion within a photocurable silicone/acrylate blend. Direct firing at 1100 °C of printed scaffolds successfully produced wollastonite-diopside glass-ceramic scaffolds, with a very fine crystal distribution. The strength-to-density was tuned by operating either on the topology of scaffolds or on the firing atmosphere (passing from air to N2)

Bioactive sphene-based ceramic coatings on cpTi substrates for dental implants: An in vitro study

Titanium implant surface modifications have been widely investigated to favor the process of osseointegration. The present work aimed to evaluate the effect of sphene (CaTiSiO5) biocoating, on titanium substrates, on the in vitro osteogenic differentiation of Human Adipose-Derived Stem Cells (hADSCs). Sphene bioceramic coatings were prepared using preceramic polymers and nano-sized active fillers and deposited by spray coating. Scanning Electron Microscopy (SEM) analysis, surface roughness measurements and X-ray diffraction analysis were performed. The chemical stability of the coatings in Tris-HCl solution was investigated. In vitro studies were performed by means of proliferation test of hADSCs seeded on coated and uncoated samples after 21 days. Methyl Thiazolyl-Tetrazolium (MTT) test and immunofluorescent staining with phalloidin confirmed the in vitro biocompatibility of both substrates. In vitro osteogenic differentiation of the cells was evaluated using Alizarin Red S staining and quantification assay and real-time PCR (Polymerase Chain Reaction). When hADSCs were cultured in the presence of Osteogenic Differentiation Medium, a significantly higher accumulation of calcium deposits onto the sphene-coated surfaces than on uncoated controls was detected. Osteogenic differentiation on both samples was confirmed by PCR. The proposed coating seems to be promising for dental and orthopedic implants, in terms of composition and deposition technology

Glass powders and reactive silicone binder: Application to digital light processing of bioactive glass-ceramic scaffolds

Powdered \u2018silica-defective glasses\u2019, mixed with silicones, have been already shown as a promising solution for the sintering, in air, of glass-ceramics with complex geometries. A fundamental advantage of the approach is the fact silicones act as binders up to the firing temperature, at which they transform into silica. A specified \u2018target\u2019 glass-ceramic formulation is achieved through the interaction between glass powders and the binder-derived silica. The present paper is dedicated to the extension of the approach to the digital light processing of reticulated glass-ceramic scaffolds, for tissue engineering applications, starting from glass powders suspended in an engineered photocurable silicone-based binder. The silicone component, besides providing an extended binding action up to the maximum firing temperature, stabilizes the 3D-printed shapes during sintering. The formation of a rigid silica skeleton, from the transformation of the silicone binder, prevents from excessive viscous flow of softened glass. The final phase assemblage does not depend simply on glass devitrification but also on the glass/silica skeleton interaction

Engineering of Silicone-based Mixtures for the Digital Light Processing of Åkermanite Scaffolds

Abstract Silicones mixed with oxide fillers are interesting precursors for several bioactive glass-ceramics. A key point is represented by the coupling of synthesis and shaping, since highly porous bodies, in form of foams or scaffolds, are first manufactured with silicones in the polymeric state, at low temperature, and later subjected to ceramic transformation. After successful application of direct ink writing, the present study illustrates the tuning of silicone-based mixtures in order to form akermanite (Ca2MgSi2O7) reticulated scaffolds by digital light processing. This implied the selection of commercial silicones, producing stable and homogeneous blends with a photocurable resin and enabling the manufacturing of defect-free printed scaffolds, before and after firing, without fillers. The blends were further refined with the introduction of fillers, followed by firing at 1100 °C, in air. Optimized samples (from H44 resin) and reactive fillers (including up to 4.5 wt.% borax additive), led to crack-free and phase-pure scaffolds with microporous struts

Bioactive glass-ceramic foam scaffolds from "inorganic gel casting" and sinter-crystallization

Highly porous bioactive glass-ceramic scaffolds were effectively fabricated by an inorganic gel casting technique, based on alkali activation and gelification, followed by viscous flow sintering. Glass powders, already known to yield a bioactive sintered glass-ceramic (CEL2) were dispersed in an alkaline solution, with partial dissolution of glass powders. The obtained glass suspensions underwent progressive hardening, by curing at low temperature (40 °C), owing to the formation of a C–S–H (calcium silicate hydrate) gel. As successful direct foaming was achieved by vigorous mechanical stirring of gelified suspensions, comprising also a surfactant. The developed cellular structures were later heat-treated at 900–1000 C, to form CEL2 glass-ceramic foams, featuring an abundant total porosity (from 60% to 80%) and well-interconnected macro- and micro-sized cells. The developed foams possessed a compressive strength from 2.5 to 5 MPa, which is in the range of human trabecular bone strength. Therefore, CEL2 glass-ceramics can be proposed for bone substitutions