Publications by authors named "Chiara Vitale-Brovarone"

64 Publications

Biomimetic Scaffolds Obtained by Electrospinning of Collagen-Based Materials: Strategies to Hinder the Protein Denaturation.

Materials (Basel) 2021 Aug 4;14(16). Epub 2021 Aug 4.

Complex Tissue Regeneration Department, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ET Maastricht, The Netherlands.

The use of biomaterials and scaffolds to boost bone regeneration is increasingly gaining interest as a complementary method to the standard surgical and pharmacological treatments in case of severe injuries and pathological conditions. In this frame, the selection of biomaterials and the accurate assessment of the manufacturing procedures are considered key factors in the design of constructs able to resemble the features of the native tissue and effectively induce specific cell responses. Accordingly, composite scaffolds based on type-I-collagen can mimic the composition of bone extracellular matrix (ECM), while electrospinning technologies can be exploited to produce nanofibrous matrices to resemble its architectural organization. However, the combination of collagen and electrospinning reported several complications due to the frequent denaturation of the protein and the variability of results according to collagen origin, concentration, and solvent. In this context, the strategies optimized in this study enabled the preparation of collagen-based electrospun scaffolds characterized by about 100 nm fibers, preserving the physico-chemical properties of the protein thanks to the use of an acetic acid-based solvent. Moreover, nanoparticles of mesoporous bioactive glasses were combined with the optimized collagen formulation, proving the successful design of composite scaffolds resembling the morphological features of bone ECM at the nanoscale.
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http://dx.doi.org/10.3390/ma14164360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400144PMC
August 2021

PEG-Coated Large Mesoporous Silicas as Smart Platform for Protein Delivery and Their Use in a Collagen-Based Formulation for 3D Printing.

Int J Mol Sci 2021 Feb 9;22(4). Epub 2021 Feb 9.

Department of Applied Science and Technology, Politecnico di Torino, 10029 Torino, Italy.

Silica-based mesoporous systems have gained great interest in drug delivery applications due to their excellent biocompatibility and high loading capability. However, these materials face challenges in terms of pore-size limitations since they are characterized by nanopores ranging between 6-8 nm and thus unsuitable to host large molecular weight molecules such as proteins, enzymes and growth factors (GFs). In this work, for an application in the field of bone regeneration, large-pore mesoporous silicas (LPMSs) were developed to vehicle large biomolecules and release them under a pH stimulus. Considering bone remodeling, the proposed pH-triggered mechanism aims to mimic the release of GFs encased in the bone matrix due to bone resorption by osteoclasts (OCs) and the associated pH drop. To this aim, LPMSs were prepared by using 1,3,5-trimethyl benzene (TMB) as a swelling agent and the synthesis solution was hydrothermally treated and the influence of different process temperatures and durations on the resulting mesostructure was investigated. The synthesized particles exhibited a cage-like mesoporous structure with accessible pores of diameter up to 23 nm. LPMSs produced at 140 °C for 24 h showed the best compromise in terms of specific surface area, pores size and shape and hence, were selected for further experiments. Horseradish peroxidase (HRP) was used as model protein to evaluate the ability of the LPMSs to adsorb and release large biomolecules. After HRP-loading, LPMSs were coated with a pH-responsive polymer, poly(ethylene glycol) (PEG), allowing the release of the incorporated biomolecules in response to a pH decrease, in an attempt to mimic GFs release in bone under the acidic pH generated by the resorption activity of OCs. The reported results proved that PEG-coated carriers released HRP more quickly in an acidic environment, due to the protonation of PEG at low pH that catalyzes polymer hydrolysis reaction. Our findings indicate that LPMSs could be used as carriers to deliver large biomolecules and prove the effectiveness of PEG as pH-responsive coating. Finally, as proof of concept, a collagen-based suspension was obtained by incorporating PEG-coated LPMS carriers into a type I collagen matrix with the aim of designing a hybrid formulation for 3D-printing of bone scaffolds.
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http://dx.doi.org/10.3390/ijms22041718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914545PMC
February 2021

Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study.

Nanomaterials (Basel) 2021 Jan 27;11(2). Epub 2021 Jan 27.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures).
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http://dx.doi.org/10.3390/nano11020321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911784PMC
January 2021

In Vivo Validation of Spray-Dried Mesoporous Bioactive Glass Microspheres Acting as Prolonged Local Release Systems for BMP-2 to Support Bone Regeneration.

Pharmaceutics 2020 Aug 28;12(9). Epub 2020 Aug 28.

Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Julius-Wolff-Institut, 13353 Berlin, Germany.

Bone morphogenetic protein-2 (BMP-2) is a known key mediator of physiological bone regeneration and is clinically approved for selected musculoskeletal interventions. Yet, broad usage of this growth factor is impeded due to side effects that are majorly evoked by high dosages and burst release kinetics. In this study, mesoporous bioactive glass microspheres (MBGs), produced by an aerosol-assisted spray-drying scalable process, were loaded with BMP-2 resulting in prolonged, low-dose BMP-2 release without affecting the material characteristics. In vitro, MBGs were found to be cytocompatible and to induce a pro-osteogenic response in primary human mesenchymal stromal cells (MSCs). In a pre-clinical rodent model, BMP-2 loaded MBGs significantly enhanced bone formation and influenced the microarchitecture of newly formed bone. The MBG carriers alone performed equal to the untreated (empty) control in most parameters tested, while additionally exerting mild pro-angiogenic effects. Using MBGs as a biocompatible, pro-regenerative carrier for local and sustained low dose BMP-2 release could limit side effects, thus enabling a safer usage of BMP-2 as a potent pro-osteogenic growth factor.
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http://dx.doi.org/10.3390/pharmaceutics12090823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559713PMC
August 2020

Collagen Hybrid Formulations for the 3D Printing of Nanostructured Bone Scaffolds: An Optimized Genipin-Crosslinking Strategy.

Nanomaterials (Basel) 2020 Aug 27;10(9). Epub 2020 Aug 27.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Bone-tissue regeneration induced by biomimetic bioactive materials is the most promising approach alternative to the clinical ones used to treat bone loss caused by trauma or diseases such as osteoporosis. The goal is to design nanostructured bioactive constructs able to reproduce the physiological environment: By mimicking the natural features of bone tissue, the cell behavior during the regeneration process may be addressed. At present, 3D-printing technologies are the only techniques able to design complex structures avoiding constraints of final shape and porosity. However, this type of biofabrication requires complex optimization of biomaterial formulations in terms of specific rheological and mechanical properties while preserving high biocompatibility. In this work, we combined nano-sized mesoporous bioactive glasses enriched with strontium ions with type I collagen, to formulate a bioactive ink for 3D-printing technologies. Moreover, to avoid the premature release of strontium ions within the crosslinking medium and to significantly increase the material mechanical and thermal stability, we applied an optimized chemical treatment using ethanol-dissolved genipin solutions. The high biocompatibility of the hybrid system was confirmed by using MG-63 and Saos-2 osteoblast-like cell lines, further highlighting the great potential of the innovative nanocomposite for the design of bone-like scaffolds.
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http://dx.doi.org/10.3390/nano10091681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558137PMC
August 2020

Analysis of multiple protein detection methods in human osteoporotic bone extracellular matrix: From literature to practice.

Bone 2020 08 13;137:115363. Epub 2020 Apr 13.

Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy.

The punctual analysis of bone Extracellular Matrix (ECM) proteins represents a pivotal point for medical research in bone diseases like osteoporosis. Studies in this field, historically done to appreciate bone biology, were mainly conducted on animal samples and, up to today, only a few studies on protein detection in human bone are present. The challenges in bone ECM protein extraction and quantitation protocols are related to both the separation of proteins from the mineral content (i.e. hydroxyapatite) and the difficulty of avoiding protein denaturation during the extraction processes. The aim of the present work was to define appropriate protocol(s) for bone ECM protein extraction that could be applied to investigate both normal and pathological conditions. We compared and optimised some of the most used protocols present in the literature, modifying the protein precipitation method, the buffer used for resuspension and/or the volume of reagent used. Bradford and BCA assays and Western Blotting were used to evaluate the variations in the total protein recovery and the amount of selected proteins (Type I Collagen, TGF-β, IGF-1, Decorin, Osteopontin, Bone Sialoprotein-2 and Osteocalcin). Collectively, we were capable to draw-up two single-extract protocols with optimal recovery and ideal protein content, that can be used for a detailed analysis of ECM proteins in pathological bone samples. Time-consuming multi-extract procedures, optimised in their precipitation methods, are however crucial for a precise detection of specific proteins, like osteocalcin. As the matter of fact, also the demineralization processes, commonly suggested and performed in several protocols, could hinder an accurate protein detection, thus inherently affecting the study of a pathological bone ECM. This study represents a starting point for the definition of appropriate strategies in the study of bone extracellular matrix proteins involved in the onset and maintenance of bone diseases, as well as a tool for the development of customized scaffolds capable to modulate a proper feedback loop in bone remodelling, altered in case of diseases like osteoporosis.
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http://dx.doi.org/10.1016/j.bone.2020.115363DOI Listing
August 2020

Multifunctional Copper-Containing Mesoporous Glass Nanoparticles as Antibacterial and Proangiogenic Agents for Chronic Wounds.

Front Bioeng Biotechnol 2020 31;8:246. Epub 2020 Mar 31.

School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.

The physiological wound healing process involves a cascade of events which could be affected by several factors resulting in chronic, non-healing wounds. The latter represent a great burden especially when bacterial biofilms are formed. The rise in antibiotic resistance amongst infectious microorganisms leads to the need of novel approaches to treat this clinical issue. In this context, the use of advanced biomaterials, which can enhance the physiological expression and secretion of the growth factors involved in the wound healing process, is gaining increasing attention as a robust and appealing alternative approach. Among them, mesoporous glasses are of particular interest due to their excellent textural properties and to the possibility of incorporating and releasing specific therapeutic species, such as metallic ions. One of the most attractive therapeutic ions is copper thanks to its proangiogenic and antibacterial effects. In this contribution, copper containing mesoporous glass nanoparticles were proposed as a multifunctional device to treat chronic wounds. The developed nanoparticles evidenced a very high specific surface area (740 m/g), uniform pores of 4 nm and an almost total release of the therapeutic ion within 72 h of soaking. The produced nanoparticles were biocompatible and, when tested against Gram positive and Gram negative bacterial species, demonstrated antibacterial activity against both planktonic and biofilm bacteria in 2D cell monolayers, and in a 3D human model of infected skin. Their proangiogenic effect was tested with both the aortic ring and the chick chorioallantoic membrane assays and an increase in endothelial cell outgrowth at a concentration range between 30 and 300 ng/mL was shown. Overall, in this study biocompatible, multifunctional Cu-containing mesoporous glass nanoparticles were successfully produced and demonstrated to exert both antibacterial and proangiogenic effects.
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http://dx.doi.org/10.3389/fbioe.2020.00246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136418PMC
March 2020

Co-culture systems of osteoblasts and osteoclasts: Simulating in vitro bone remodeling in regenerative approaches.

Acta Biomater 2020 05 3;108:22-45. Epub 2020 Apr 3.

Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.

Bone is an extremely dynamic tissue, undergoing continuous remodeling for its whole lifetime, but its regeneration or augmentation due to bone loss or defects are not always easy to obtain. Bone tissue engineering (BTE) is a promising approach, and its success often relies on a "smart" scaffold, as a support to host and guide bone formation through bone cell precursors. Bone homeostasis is maintained by osteoblasts (OBs) and osteoclasts (OCs) within the basic multicellular unit, in a consecutive cycle of resorption and formation. Therefore, a functional scaffold should allow the best possible OB/OC cooperation for bone remodeling, as happens within the bone extracellular matrix in the body. In the present work OB/OC co-culture models, with and without scaffolds, are reviewed. These experimental systems are intended for different targets, including bone remodeling simulation, drug testing and the assessment of biomaterials and 3D scaffolds for BTE. As a consequence, several parameters, such as cell type, cell ratio, culture medium and inducers, culture times and setpoints, assay methods, etc. vary greatly. This review identifies and systematically reports the in vitro methods explored up to now, which, as they allow cellular communication, more closely resemble bone remodeling and/or the regeneration process in the framework of BTE. STATEMENT OF SIGNIFICANCE: Bone is a dynamic tissue under continuous remodeling, but spontaneous healing may fail in the case of excessive bone loss which often requires valid alternatives to conventional treatments to restore bone integrity, like bone tissue engineering (BTE). Pre-clinical evaluation of scaffolds for BTE requires in vitro testing where co-cultures combining innovative materials with osteoblasts (OBs) and osteoclasts (OCs) closely mimic the in vivo repair process. This review considers the direct and indirect OB/OC co-cultures relevant to BTE, from the early mouse-cell models to the recent bone regenerative systems. The co-culture modeling of bone microenvironment provides reliable information on bone cell cross-talk. Starting from improved knowledge on bone remodeling, bone disease mechanisms may be understood and new BTE solutions are designed.
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http://dx.doi.org/10.1016/j.actbio.2020.03.043DOI Listing
May 2020

Antioxidant mesoporous Ce-doped bioactive glass nanoparticles with anti-inflammatory and pro-osteogenic activities.

Mater Today Bio 2020 Jan 9;5:100041. Epub 2020 Jan 9.

Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, Germany.

Mesoporous bioactive glass nanoparticles (MBGNs) are emerging biomaterials for bone repair/regeneration, considering their favorable pro-osteogenic and proangiogenic activities. To further improve their therapeutic effects, the endowment of MBGNs with additional antioxidant properties is of particular interest to target oxidative stress related to bone remodeling and diseases. To this end, we developed antioxidant cerium-containing MBGNs (Ce-MBGNs) (particle size of 100-300 ​nm) by using a postimpregnation strategy to incorporate Ce, through which the shape, pore structure, and dispersity of the nanoparticles were preserved. The incorporated amount of Ce could be tailored by adjusting the concentration of the Ce precursor solution. When impregnated at a relatively low temperature (20 ​°C), Ce-MBGNs containing either 1.8 or 2.8 ​mol% of Ce were produced, while the formation of by-product cerium oxide nanoparticles (nanoceria) could be avoided. In both developed Ce-MBGNs, the concentration of Ce was higher than that of Ce, while the relative molar percentage of Ce was similar (∼74%) in both Ce-MBGNs. The obtained Ce-MBGNs were evidenced to be non-cytotoxic against fibroblasts at the concentration of 1 ​mg/mL. Moreover, the incorporation of Ce into MBGNs significantly reduced the expression of oxidative stress-related genes in macrophages (J774a.1). Particularly in the presence of pro-oxidation agents, Ce-MBGNs could downregulate the expression of oxidative stress-related genes in comparsion with the polystyrene plates (control). When cultured with Ce-MBGNs, the expression of proinflammatory-related genes in macrophages could also be downregulated in comparsion with MBGNs and the control. Ce-MBGNs also exhibited pro-osteogenic activities through suppressing pro-osteoclastogenic responses. The obtained results highlight the great potential of the developed Ce-MBGNs in a variety of biomedical applications, particularly in treating bone defects under inflammatory conditions, considering their antioxidant, anti-inflammatory, and pro-osteogenesis activities.
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http://dx.doi.org/10.1016/j.mtbio.2020.100041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083763PMC
January 2020

Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context.

Int J Nanomedicine 2019 31;14:10147-10164. Epub 2019 Dec 31.

Nobil Bio Ricerche Srl, Portacomaro 14037, AT, Italy.

Introduction: Silver decorated mesoporous carbons are interesting systems that may offer effective solutions for advanced wound care products by combining the well-known anti-microbial activity of silver nanoparticles with the versatile properties of ordered mesoporous carbons. Silver is being used as a topical antimicrobial agent, especially in wound repair. However, while silver shows bactericidal properties, it is also cytotoxic at high concentrations. Therefore, the incorporation of silver into ordered mesoporous carbons allows to exploit both silver's biological effects and mesoporous carbons' biocompatibility and versatility with the purpose of conceiving silver-doped materials in light of the growing health concern in wound care.

Methods: The wound healing potential of an ordered mesoporous carbon also doped with two different loadings of silver nanoparticles (2 wt% and 10 wt%), was investigated through a biological assessment study based on different assays (cell viability, inflammation, antibacterial tests, macrophage-conditioned fibroblast and human keratinocyte cell cultures).

Results: The results show silver-doped ordered mesoporous carbons to positively condition cell viability, with a cell viability percentage >70% even for 10 wt% Ag, to modulate the expression of inflammatory cytokines and of genes involved in tissue repair (KRT6a, VEGFA, IVN) and remodeling (MMP9, TIMP3) in different cell systems. Furthermore, along with the biocompatibility and the bioactivity, the silver-doped ordered mesoporous carbons still retain an antibacterial effect, as shown by a maximum of 13.1% of inhibited area in the Halo test. The obtained results clearly showed that the silver-doped ordered mesoporous carbons exhibit both good biocompatibility and antibacterial effect with enhanced re-epithelialization, angiogenesis promotion and tissue regeneration.

Discussion: These findings suggest that the exceptional properties of silver-doped ordered mesoporous carbons could be exploited in the treatment of acute and chronic wounds and that such carbon materials could be potential candidates for use in medical devices for wound healing purposes, in particular, the 10 wt% loading, as the results showed to be the most effective.
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http://dx.doi.org/10.2147/IJN.S234393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942531PMC
April 2020

Strontium-releasing mesoporous bioactive glasses with anti-adhesive zwitterionic surface as advanced biomaterials for bone tissue regeneration.

J Colloid Interface Sci 2020 Mar 14;563:92-103. Epub 2019 Dec 14.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, Italy. Electronic address:

Hypothesis: The treatment of bone fractures still represents a challenging clinical issue when complications due to impaired bone remodelling (i.e. osteoporosis) or infections occur. These clinical needs still require a radical improvement of the existing therapeutic approach through the design of advanced biomaterials combining the ability to promote bone regeneration with anti-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), which are able to exert a pro-osteogenic effect by releasing Sr ions, have been successfully functionalised to provide mixed-charge (NH/COO) surface groups with anti-adhesive abilities.

Experiments: Sr-MBG have been post-synthesis modified by co-grafting hydrolysable short chain silanes containing amino (aminopropylsilanetriol) and carboxylate (carboxyethylsilanetriol) moieties to achieve a zwitterionic zero-charge surface. The final system was then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and anti-adhesive capabilities.

Findings: After zwitterionization the in vitro bioactivity was maintained, as well as the ability to release Sr ions which are capable of inducing a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in pre-osteoblastic MC3T3-E1 up to the concentration of 75 µg/mL. Finally, the zwitterionic Sr-MBGs showed a significant reduction of serum protein adhesion with respect to the pristine ones. These results open promising future expectations in the design of nanosystems which combine pro-osteogenic and anti-adhesive properties.
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http://dx.doi.org/10.1016/j.jcis.2019.12.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116262PMC
March 2020

Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: a short review.

Biomed Mater 2020 02 27;15(2):022001. Epub 2020 Feb 27.

In the last decades, many research groups have experimented the synthesis of hydroxyapatite (HA) for bone tissue application obtaining products with different shapes and dimensions. This review aims to summarise and critically analyse the most used methods to prepare physiologic-like nano-HA, in the form of plates or rods, similar to the HA present in the human bones. Moreover, mesoporous HA has gained increasing interest in the biomedical field due its pecualiar structural features, such as high surface area and accessible mesoporous volume, which is known to confer enhanced biological behaviour and the possibility to act as nanocarriers of functional agents for bone-related therapies. For this reason, more recent studies related to the synthesis of mesoporous HA, with physiological-like morphology, are also considered in this review. Since a wide class of surfactant molecules plays an essential role both in the shape and size control of HA crystals and in the formation of mesoporosity, a section devoted to the mechanisms of action of several surfactants is also provided.
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http://dx.doi.org/10.1088/1748-605X/ab5f1aDOI Listing
February 2020

Development and Biocompatibility of Collagen-Based Composites Enriched with Nanoparticles of Strontium Containing Mesoporous Glass.

Materials (Basel) 2019 Nov 11;12(22). Epub 2019 Nov 11.

Applied Science and Technology Department, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

In the last years bone tissue engineering has been increasingly indicated as a valid solution to meet the challenging requirements for a healthy bone regeneration in case of bone loss or fracture. In such a context, bioactive glasses have already proved their great potential in promoting the regeneration of new bone tissue due to their high bioactivity. In addition, their composition and structure enable us to incorporate and subsequently release therapeutic ions such as strontium, enhancing the osteogenic properties of the material. The incorporation of these inorganic systems in polymeric matrices enables the formulation of composite systems suitable for the design of bone scaffolds or delivery platforms. Among the natural polymers, type I collagen represents the main organic phase of bone and thus is a good candidate to develop biomimetic bioactive systems for bone tissue regeneration. However, alongside the specific composition and structure, the key factor in the design of new biosystems is creating a suitable interaction with cells and the host tissue. In this scenario, the presented study aimed at combining nano-sized mesoporous bioactive glasses produced by means of a sol-gel route with type I collagen in order to develop a bioactive hybrid formulation suitable for bone tissue engineering applications. The designed system has been fully characterized in terms of physico-chemical and morphological analyses and the ability to release Sr ions has been studied observing a more sustained profile in presence of the collagenous matrix. With the aim to improve the mechanical and thermal stability of the resulting hybrid system, a chemical crosslinking approach using 4-star poly (ethylene glycol) ether tetrasuccinimidyl glutarate (4-StarPEG) has been explored. The biocompatibility of both non-crosslinked and 4-StarPEG crosslinked systems was evaluated by in vitro tests with human osteoblast-like MG-63 cells. Collected results confirmed the high biocompatibility of composites, showing a good viability and adhesion of cells when cultured onto the biomaterial samples.
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http://dx.doi.org/10.3390/ma12223719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888293PMC
November 2019

Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel/Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs.

Pharmaceutics 2019 Oct 1;11(10). Epub 2019 Oct 1.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% /). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3-5 min). Cu and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu, respectively). Additionally, released Cu species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.
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http://dx.doi.org/10.3390/pharmaceutics11100501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835912PMC
October 2019

Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis.

Cytokine Growth Factor Rev 2019 10 13;49:59-69. Epub 2019 Sep 13.

Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, 60126, Ancona, Italy.

Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-β, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling.
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http://dx.doi.org/10.1016/j.cytogfr.2019.09.001DOI Listing
October 2019

Osteoporosis-related variations of trabecular bone properties of proximal human humeral heads at different scale lengths.

J Mech Behav Biomed Mater 2019 12 26;100:103373. Epub 2019 Jul 26.

Politecnico di Torino, Department of Applied Science and Technology, Corso Duca degli Abruzzi 24, 10129, Torino, Italy. Electronic address:

Osteoporosis (OP) is a skeletal disorder responsible for the weakening of the bone structure and, consequently, for an increased fracture risk in the elderly population. In the past, bone mineral density (BMD) variation was considered the best OP indicator, but recently the focus has shifted toward the variation of microstructural bone parameters. This work is based on the characterisation of 8-mm cylindrical biopsies harvested from proximal humeral heads belonging to healthy and osteoporotic patients, in order to assess the OP-related variations of bone properties at different scale lengths. In particular, bone biopsies underwent micro-computed tomography analysis to study the most relevant features of bone architecture and extrapolate the tissue mineral density (TMD) value of bone trabeculae. Compression tests and nanoindentations were performed to investigate the macro- and micromechanical properties of bone biopsies, respectively. In addition, XRD analyses were performed to obtain the mean hydroxyapatite (HA) crystallite size, while Raman spectroscopy investigated the collagen secondary structure. Thermogravimetric analysis was performed to evaluate the ratio between organic and inorganic phases. From the obtained results, OP samples showed a more anisotropic and less interconnected structure responsible for reduced compression strength. From this, it can be supposed that OP caused an alteration of bone structure that led to inferior macroscopic mechanical properties. Furthermore, OP samples possessed higher TMD and bigger HA crystals that are correlated to an increase of the hardness value obtained by means of nanoindentation. This less controlled HA crystal growth is probably due to an alteration of the organic matrix structure, as revealed by the increase of the random coil contribution in the Raman spectra of the OP bone. This higher crystal content led to an increase in trabecular density and hardness. In conclusion, the obtained data showed that OP affects bone properties at different scale lengths causing an alteration of its morphological, structural and mechanical features.
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http://dx.doi.org/10.1016/j.jmbbm.2019.103373DOI Listing
December 2019

Ag modified mesoporous bioactive glass nanoparticles for enhanced antibacterial activity in 3D infected skin model.

Mater Sci Eng C Mater Biol Appl 2019 Oct 17;103:109764. Epub 2019 May 17.

Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address:

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO-CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.
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http://dx.doi.org/10.1016/j.msec.2019.109764DOI Listing
October 2019

In Vitro Assessment of Bioactive Glass Coatings on Alumina/Zirconia Composite Implants for Potential Use in Prosthetic Applications.

Int J Mol Sci 2019 Feb 8;20(3). Epub 2019 Feb 8.

Politecnico di Torino, Department of Applied Science and Technology, Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Achieving the stable osteointegration of prosthetic implants is one of the great challenges of modern orthopedic surgery. The fixation of ceramic acetabular cups of hip joint prostheses is usually achieved using a metal shell provided with screws or pegs that penetrate into the host pelvic bone. The deposition of bioactive coatings on the implant surface to be put in contact with bone could be a valuable strategy to promote a more "physiological" osteointegration. In this work, bioactive glass porous coatings were manufactured on the top of alumina/zirconia composite implants by two different methods, i.e., sponge replication and laser cladding. The coated samples underwent immersion studies in Kokubo's simulated body fluid (SBF) to assess in vitro bioactivity and were found to exhibit an excellent hydroxyapatite-forming ability, which is key to allow bonding to bone. Biological tests using mesenchymal stem and osteoblast-like cells revealed the good biocompatibility of both types of materials. Furthermore, a higher level of mineralization was induced by the sponge-replicated coatings at 10 days. Overall, these results are highly promising and encourage further research on these materials.
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http://dx.doi.org/10.3390/ijms20030722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387312PMC
February 2019

Newly-designed collagen/polyurethane bioartificial blend as coating on bioactive glass-ceramics for bone tissue engineering applications.

Mater Sci Eng C Mater Biol Appl 2019 Mar 10;96:218-233. Epub 2018 Nov 10.

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy. Electronic address:

In the present work, a new combination of synthetic and natural biomaterials is proposed for bone tissue engineering (BTE) applications. In order to mimic the inorganic and organic phases of bone extracellular matrix (ECM), a bioactive glass-ceramic deriving from a SiO-PO-CaO-MgO-NaO-KO parent glass, acting as a substrate in form of a slice, was surface-functionalised with a type I collagen-based coating. In particular, the collagen was blended with a water soluble polyurethane (PUR), synthesised from poly(ethylene glycol), 1,6-hexamethylene diisocyanate and N-BOC-serinol. The PUR was designed to expose amino groups on the polymeric chain, which can be exploited for the blend stabilisation through crosslinking. The newly synthesised PUR demonstrated to be non-cytotoxic, as assessed by a biological test with MG-63 osteoblast-like cells. The collagen/PUR blend showed good biocompatibility as well. The polymeric coating on the glass-ceramic samples was produced by surface-silanisation, followed by further chemical grafting of the blend, using genipin as a crosslinker. The glass-ceramic surface was characterised at each functionalisation step, demonstrating that the procedure allowed obtaining a covalent link between the blend and the substrate. Finally, biological tests performed using human periosteal derived precursor cells demonstrated that the proposed polymer-coated material was a good substrate for bone cell adhesion and growth, and a good candidate to mimic the composite nature of the bone ECM.
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http://dx.doi.org/10.1016/j.msec.2018.11.012DOI Listing
March 2019

Graphene Oxide Finely Tunes the Bioactivity and Drug Delivery of Mesoporous ZnO Scaffolds.

ACS Appl Mater Interfaces 2019 Jan 21;11(1):449-456. Epub 2018 Dec 21.

Department of Applied Science and Technology , Politecnico di Torino , C.so Duca degli Abruzzi 24 , 10129 Turin , Italy.

Mesoporous zinc oxide (ZnO) scaffolds coated with drop-cast graphene oxide (GO) flakes are proposed to be a novel bilayer system featuring bioactivity, biocompatibility, and promising loading/release properties for controlled drug-delivery systems. The high-surface-area ZnO scaffolds show clear apatite deposition, but their particular surface chemistry and topography prevent the formation of a continuous coating, resulting in micrometric crystalline apatite aggregates after 28 days in simulated body fluid (SBF). When gentamicin sulfate (GS) is considered as a model molecule, pure ZnO scaffolds also show functional GS loading efficiency, with fast in vitro release kinetics driven by a simple diffusion mechanism. Strikingly, the bioactivity and GS delivery properties of mesoporous ZnO are efficiently triggered by drop-casting GO flakes atop the mesoporous scaffold surface. The resulting [email protected] bilayer scaffolds show the formation of a uniform apatite coating after 28 days in SBF and demonstrate a biocompatible behavior, supporting the culture of SaOS-2 osteoblast-like cells. Moreover, the GO coating also leads to a barrier-layer effect, preventing fast GS release, particularly in the short time range. This barrier effect, coupled with the existence of nanopores within the GO structure, sieves drug molecules from the mesoporous ZnO matrix and allows for a delayed release of the GS molecule. We, thus, demonstrated a new-generation [email protected] bilayer system as effective multifunctional and biocompatible scaffold for bone tissue engineering.
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http://dx.doi.org/10.1021/acsami.8b20728DOI Listing
January 2019

Glass-ceramics for cancer treatment: So close, or yet so far?

Acta Biomater 2019 01 9;83:55-70. Epub 2018 Nov 9.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 4777-14155, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran. Electronic address:

After years of research on the ability of glass-ceramics in bone regeneration, this family of biomaterials has shown revolutionary potentials in a couple of emerging applications such as cancer treatment. Although glass-ceramics have not yet reached their actual potential in cancer therapy, the relevant research activity is significantly growing in this field. It has been projected that this idea and the advent of magnetic bioactive glass-ceramics and mesoporous bioactive glasses could result in major future developments in the field of cancer. Undoubtedly, this strategy needs further developments to better answer the critical questions essential for clinical usage. This review aims to address the existing research developments on glass-ceramics for cancer treatment, starting with the current status and moving to future advances. STATEMENT OF SIGNIFICANCE: Although glass-ceramics have not yet reached their potential in cancer therapy, research activity is significantly growing. It has been speculated that this idea and the advent of modern glass-ceramics could result in significant future advances. Undoubtedly, this strategy needs further investigations and many critical questions have to be answered before it can be successfully applied for cancer treatment. This paper reviews the current state-of-the-art, starting with current products and moving onto recent developments in this field. According to our knowledge, there is a lack of a systematic review on the importance and developments of magnetic bioactive glass-ceramics and mesoporous bioactive glasses for cancer treatment, and it is expected that this review will be of interest to those working in this area.
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http://dx.doi.org/10.1016/j.actbio.2018.11.013DOI Listing
January 2019

Production and Physicochemical Characterization of Cu-Doped Silicate Bioceramic Scaffolds.

Materials (Basel) 2018 Aug 24;11(9). Epub 2018 Aug 24.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Development of ion-releasing implantable biomaterials is a valuable approach for advanced medical therapies. In the effort of tackling this challenge, we explored the feasibility of porous bioceramic scaffolds releasing copper ions, which are potentially able to elicit angiogenetic and antibacterial effects. First, small amounts of CuO were incorporated in the base silicate glass during melting and the obtained powders were further processed to fabricate glass⁻ceramic scaffolds by sponge replica method followed by sinter crystallization. As the release of copper ions from these foams in simulated body fluid (SBF) was very limited, a second processing strategy was developed. Silicate glass⁻ceramic scaffolds were coated with a layer of Cu-doped mesoporous glass, which exhibited favorable textural properties (ultrahigh specific surface area >200 m²/g, mesopore size about 5 nm) for modulating the release of copper. All the produced scaffolds, containing biocompatible crystals of wollastonite (CaSiO₃), revealed high stability in a biological environment. Furthermore, the materials had adequate compressive strength (>10 MPa) for allowing safe manipulation during surgery. Overall, the results achieved in the present work suggest that these Cu-doped glass-derived scaffolds show promise for biomedical application and motivate further investigation of their suitability from a biological viewpoint.
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http://dx.doi.org/10.3390/ma11091524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164809PMC
August 2018

Type I Collagen and Strontium-Containing Mesoporous Glass Particles as Hybrid Material for 3D Printing of Bone-Like Materials.

Materials (Basel) 2018 Apr 28;11(5). Epub 2018 Apr 28.

Politecnico di Torino, Department of Applied Science and Technology, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Bone tissue engineering offers an alternative promising solution to treat a large number of bone injuries with special focus on pathological conditions, such as osteoporosis. In this scenario, the bone tissue regeneration may be promoted using bioactive and biomimetic materials able to direct cell response, while the desired scaffold architecture can be tailored by means of 3D printing technologies. In this context, our study aimed to develop a hybrid bioactive material suitable for 3D printing of scaffolds mimicking the natural composition and structure of healthy bone. Type I collagen and strontium-containing mesoporous bioactive glasses were combined to obtain suspensions able to perform a sol-gel transition under physiological conditions. Field emission scanning electron microscopy (FESEM) analyses confirmed the formation of fibrous nanostructures homogeneously embedding inorganic particles, whereas bioactivity studies demonstrated the large calcium phosphate deposition. The high-water content promoted the strontium ion release from the embedded glass particles, potentially enhancing the osteogenic behaviour of the composite. Furthermore, the suspension printability was assessed by means of rheological studies and preliminary extrusion tests, showing shear thinning and fast material recovery upon deposition. In conclusion, the reported results suggest that promising hybrid systems suitable for 3D printing of bioactive scaffolds for bone tissue engineering have been developed.
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http://dx.doi.org/10.3390/ma11050700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978077PMC
April 2018

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses.

Materials (Basel) 2018 Apr 26;11(5). Epub 2018 Apr 26.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

Over the recent years, mesoporous bioactive glasses (MBGs) gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO₂⁻CaO system and containing different percentages (2 and 4 mol %) of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N₂ adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929) viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis.
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http://dx.doi.org/10.3390/ma11050678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978055PMC
April 2018

Bioactive Glass-Ceramic Foam Scaffolds from 'Inorganic Gel Casting' and Sinter-Crystallization.

Materials (Basel) 2018 Feb 27;11(3). Epub 2018 Feb 27.

Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy.

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.
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http://dx.doi.org/10.3390/ma11030349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872928PMC
February 2018

Composite Biomaterials Based on Sol-Gel Mesoporous Silicate Glasses: A Review.

Bioengineering (Basel) 2017 Feb 23;4(1). Epub 2017 Feb 23.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino 10129, Italy.

Bioactive glasses are able to bond to bone and stimulate the growth of new tissue while dissolving over time, which makes them ideal materials for regenerative medicine. The advent of mesoporous glasses, which are typically synthesized via sol-gel routes, allowed researchers to develop a broad and versatile class of novel biomaterials that combine superior bone regenerative potential (compared to traditional melt-derived glasses) with the ability of incorporating drugs and various biomolecules for targeted therapy in situ. Mesoporous glass particles can be directly embedded as a bioactive phase within a non-porous (e.g., microspheres), porous (3D scaffolds) or injectable matrix, or be processed to manufacture a surface coating on inorganic or organic (macro)porous substrates, thereby obtaining hierarchical structures with multiscale porosity. This review provides a picture of composite systems and coatings based on mesoporous glasses and highlights the challenges for the future, including the great potential of inorganic-organic hybrid sol-gel biomaterials.
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http://dx.doi.org/10.3390/bioengineering4010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590434PMC
February 2017

Copper-containing mesoporous bioactive glass nanoparticles as multifunctional agent for bone regeneration.

Acta Biomater 2017 06 12;55:493-504. Epub 2017 Apr 12.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy. Electronic address:

The application of mesoporous bioactive glasses (MBGs) containing controllable amount of different ions, with the aim to impart antibacterial activity, as well as stimulation of osteogenesis and angiogenesis, is attracting an increasing interest. In this contribution, in order to endow nano-sized MBG with additional biological functions, the framework of a binary SiO-CaO mesoporous glass was modified with different concentrations of copper ions (2 and 5%mol.), through a one-pot ultrasound-assisted sol-gel procedure. The Cu-containing MBG (2%mol.) showed high exposed surface area (550mg), uniform mesoporous channels (2.6nm), remarkable in vitro bioactive behaviour and sustained release of Cu ions. Cu-MBG nanoparticles and their ionic dissolution extracts exhibited antibacterial effect against three different bacteria strains, E. coli, S. aureus, S. epidermidis, and the ability to inhibit and disperse the biofilm produced by S. epidermidis. The obtained results suggest that the developed material, which combines in single multifunctional agent excellent bioactivity and antimicrobial ability, offers promising opportunities for the prevention of infectious diseases and the effective treatment of bone defects.

Statement Of Significance: In order to endow mesoporous bioactive glass, characterized by excellent bioactive properties, with additional biological functions, Cu-doped mesoporous SiO-CaO glass (Cu-MBG) in the form of nanoparticles was prepared by an ultra-sound assisted one pot synthesis. The analysis of the bacterial viability, using different bacterial strains, and the morphological observation of the biofilm produced by the Staphylococcus epidermidis, revealed the antimicrobial effectiveness of the Cu-MBG and the relative ionic extracts against both the bacterial growth and the biofilm formation/dispersion, providing a true alternative to traditional antibiotic systemic therapies. The proposed multifunctional agent represents a promising and versatile platform for bone and soft tissues regeneration.
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http://dx.doi.org/10.1016/j.actbio.2017.04.012DOI Listing
June 2017

Preparation and characterisation of an innovative injectable calcium sulphate based bone cement for vertebroplasty application.

J Mater Chem B 2017 Jan 1;5(1):102-115. Epub 2016 Dec 1.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.

In this study, an innovative injectable and bioresorbable composite cement (Spine-Ghost) has been developed by combining a radiopaque glass-ceramic powder (SCNZgc) and spray-dried mesoporous bioactive particles (W-SC) into type III alpha calcium sulphate hemihydrate (α-CSH) (composition α-CSH/SCNZgc/W-SC, 70/20/10 wt%). The Spine-Ghost cement and pure α-CSH (as a reference) were characterised in terms of physical and mechanical properties and compared to a commercial reference (Cerament®- Bonesupport AB, Sweden). The Spine-Ghost cement had a setting time comparable with Cerament® showing a good injectability in the range of 8-20 minutes after the end of mixing. In addition, the Spine-Ghost cement showed a good radiopacity when compared with standard PMMA (BonOs Inject, aap Biomaterials GmbH Germany) and higher compressive strength when compared to healthy cancellous bone. The bioactivity of both Spine-Ghost and Cerament® was evaluated through in vitro soaking in simulated body fluid (SBF). Spine-Ghost samples were highly bioactive, inducing the precipitation of hydroxyapatite crystals in the first week of soaking in vitro. It was also found that the degradation kinetics of the Spine-Ghost cement were faster than those of pure α-CSH and comparable to those of Cerament® after approximately 1 month of soaking in SBF. Moreover, the Spine-Ghost cement was cytocompatible in indirect-contact culture in vitro. Overall results indicate that the Spine-Ghost cement might be a very good candidate for vertebroplasty application and could enhance new bone formation in vivo.
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http://dx.doi.org/10.1039/c6tb02139eDOI Listing
January 2017

Micro-CT based finite element models for elastic properties of glass-ceramic scaffolds.

J Mech Behav Biomed Mater 2017 01 23;65:248-255. Epub 2016 Aug 23.

Department of Chemistry, Materials and Chemical Engineering, Laboratory of Biological Structure Mechanics (LaBS) - Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy; I.R.C.C.S., Via R. Galeazzi 4, 20161 Milano, Italy. Electronic address:

In this study, the mechanical properties of porous glass-ceramic scaffolds are investigated by means of three-dimensional finite element models based on micro-computed tomography (micro-CT) scan data. In particular, the quantitative relationship between the morpho-architectural features of the obtained scaffolds, such as macroscopic porosity and strut thickness, and elastic properties, is sought. The macroscopic elastic properties of the scaffolds have been obtained through numerical homogenization approaches using the mechanical characteristics of the solid walls of the scaffolds (assessed through nanoindentation) as input parameters for the numerical simulations. Anisotropic mechanical properties of the produced scaffolds have also been investigated by defining a suitable anisotropy index. A comparison with morphological data obtained through the micro-CT scans is also presented. The proposed study shows that the produced glass-ceramic scaffolds exhibited a macroscopic porosity ranging between 29% and 97% which corresponds to an average stiffness ranging between 42.4GPa and 36MPa. A quantitative estimation of the isotropy of the macroscopic elastic properties has been performed showing that the samples with higher solid fractions were those closest to an isotropic material.
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http://dx.doi.org/10.1016/j.jmbbm.2016.08.020DOI Listing
January 2017

Engineered porous scaffolds for periprosthetic infection prevention.

Mater Sci Eng C Mater Biol Appl 2016 Nov 15;68:701-715. Epub 2016 Jun 15.

Department of Applied Science and Technology, Institute of Materials Physics and Engineering, Politecnico di Torino, 10121 Torino, Italy.

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (<10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection.
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http://dx.doi.org/10.1016/j.msec.2016.06.050DOI Listing
November 2016
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