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Successful tissue regeneration requires a scaffold with tailorable biodegradability, tissue-like mechanical properties, structural similarity to extracellular matrix (ECM), relevant bioactivity, and cytocompatibility. In recent years, injectable hydrogels have spurred increasing attention in translational medicine as a result of their tunable physicochemical properties in response to the surrounding environment. Furthermore, they have the potential to be implanted via minimally invasive procedures while enabling deep penetration, which is considered a feasible alternative to traditional open surgical procedures. However, polymeric hydrogels may lack sufficient stability and bioactivity in physiological environments. Composite hydrogels containing bioactive glass (BG) particulates, synergistically combining the advantages of their constituents, have emerged as multifunctional biomaterials with tailored mechanical properties and biological functionalities. This review paper highlights the recent advances in injectable composite hydrogel systems based on biodegradable polymers and BGs. The influence of BG particle geometry, composition, and concentration on gel formation, rheological and mechanical behavior as well as hydration and biodegradation of injectable hydrogels have been discussed. The applications of these composite hydrogels in tissue engineering are additionally described, with particular attention to bone and skin. Finally, the prospects and current challenges in the development of desirable injectable bioactive hydrogels for tissue regeneration are discussed to outline a roadmap for future research. Statement of significance Developing a biomaterial that can be readily available for surgery, implantable via minimally invasive procedures, and be able to effectively stimulate tissue regeneration is one of the grand challenges in modern biomedicine. This review summarizes the state-of-the-art of injectable bioactive glass-polymer composite hydrogels to address several challenges in bone and soft tissue repair. The current limitations and the latest evolutions of these composite biomaterials are critically examined, and the roles of design parameters, such as composition, concentration, and size of the bioactive phase, and polymer-glass interactions on the rheological, mechanical, biological, and overall functional performance of hydrogels are detailed. Existing results and new horizons are discussed to provide a state-of-the-art review that may be useful for both experienced and early-stage researchers in the biomaterials community.

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

Bioactive glasses are often designed as porous implantable templates in which newly-formed bone can grow in three dimensions (3D). This research work aims to investigate the bone regenerative capability of silicate bioactive glass scaffolds produced by robocasting in comparison with powder and granule-like materials (oxide system: 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5, mol.%). Morphological and compositional analyses performed by scanning electron microscopy (SEM), combined with energy dispersive spectroscopy (EDS) after the bioactivity studies in a simulated body fluid (SBF) confirmed the apatite-forming ability of the scaffolds, which is key to allowing bone-bonding in vivo. The scaffolds exhibited a clear osteogenic effect upon implantation in rabbit femur and underwent gradual resorption followed by ossification. Full resorption in favor of new bone growth was achieved within 6 months. Osseous defect healing was accompanied by the formation of mature bone with abundant osteocytes and bone marrow cells. These in vivo results support the scaffold’s suitability for application in bone tissue engineering and show promise for potential translation to clinical assessment. publishedVersion

The development of drug delivery systems minimizing the side effects of conventional chemotherapy is one of the major challenges in the field of biomaterials for cancer treatment. This work reports the formulation and characterization of oil-in-water Pluronic F127 microemulsions to enhance the bioavailability of doxorubicin (DOX). The density functional theory (DFT) calculations at the M06-2X level of theory were done to study the interaction details of DOX with ethyl butyrate, sodium caprylate, and one unit of the polymeric chain of surfactant Pluronic F127 in water solution, which are used in the synthesis process. Specifically, the quantum theory of atoms in molecules (QTAIM) analysis was performed to determine the nature of interactions. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated to show the direction of charge transfer within each complex. Furthermore, the natural bond orbital (NBO) analysis was performed on the studied systems. The size of F127/DOX microemulsion was about 7.0 nm by dynamic light scattering analysis. In vitro toxicity of standard DOX and DOX-loaded microemulsions were assessed against MCF-7 and C152 (malignant) and HUVEC (non-malignant) cell lines. Intracellular lactate dehydrogenase (LDH) leakage was evaluated as an indicator of membrane integrity. In vitro assessments revealed that Pluronic F127/DOX microemulsions caused substantial morphological changes and greater cytotoxic effects than standard DOX. Pluronic F127/DOX microemulsions were injected intraperitoneally at 12 and 24 mg/kg into rats. The free (bulk) DOX group induced severe histopathological changes and significant increases in serum kidney markers and serum liver enzymes. The 24 mg/kg dose of Pluronic F127/DOX microemulsions also induced fatty changes and elevation of serum liver enzymes and creatinine. Overall, this new drug delivery system formulation shows promise for cancer treatment and deserves to be further studied in the future.

Promoting bone healing is a key challenge in our society that can be tackled by developing new implantable biomaterials provided with regenerative properties. In this work, the coating of three-dimensional porous glass-derived scaffolds with hyaluronic acid (HA)-fatty acids was investigated for the first time. The starting scaffolds, based on bioactive silicate glass, were produced by foam replication followed by sintering; then, HA-palmitate and HA-oleate conjugate coatings were deposited on the scaffold struts through a dipping procedure. FT-IR analysis confirmed the successful deposition of the coatings on the surface and struts of the scaffolds, the foam-like architecture of which was maintained as assessed by SEM investigations. The in vitro bioactivity of the HA–fatty-acid-coated scaffolds was studied by immersion tests in simulated body fluid and the subsequent evaluation of hydroxyapatite formation. The deposition of the polymeric coating did not inhibit the apatite-forming ability of scaffolds, as revealed by the formation of nanostructured hydroxyapatite agglomerates 48 h from immersion. These promising results motivate further investigation of these novel bioactive systems, which are expected to combine the bone-bonding properties of the glass with the wound-healing promotion carried out by the polymeric conjugates.

Electrospun nanofibrous constructs based on nanoparticles and biopolymers have recently been used in tissue engineering because of their similarity to the extracellular matrix in nature. In this study, electrospun chitosan-carbon quantum dot-titanium dioxide-graphene oxide (CS-CQD-TiO2-GO) nanofibrous mats were synthesized for use as wound dressings by the electrospinning method. To increase the biodegradation rate and water resistance, the fabricated nanofibrous mats were cross-linked. SEM images showed a uniform and coherent structure of CS-CQD-TiO2-GO nanocomposites and CS-CQD-TiO2-GO electrospun nanofibers mats. FTIR analysis, XRD pattern, SEM mapping, and EDS spectrum demonstrate the accuracy of the synthesis as well as the elemental and chemical structure of the nanofibrous mat. The water contact angle indicated that the nanofibrous mat had a hydrophilic property, which is essential for controlling wound exudates. The tensile strength and elongation tests showed that the nanofibrous mat has suitable mechanical properties for wound dressing, including significant flexibility and strength. Interestingly, antimicrobial testing illustrated that the fabricated nanofibrous mat had antibacterial activity against Gram-negative and Gram-positive bacteria. Appropriate cell viability and cytocompatibility of treated mouse fibroblast NIH3T3 cells with the nanofibrous mat were determined using an MTT assay. The animal study results confirmed the proper potential of the nanofibrous mat in wound dressing applications.

Introduction: Curcumin-based products are extensively used as therapeutics in the treatment of cardiac disorders; however, there is no significant report on the curcumin potentials in cardiac tissue engineering applications. Due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties, curcumin has been demonstrated to be a promising candidate for tissue engineering (TE) applications. Areas covered: Various curcumin-containing tissue-engineered constructs have been developed for the management of soft tissue damages (such as wound injuries); hence, there are hopes for the use of this natural product in cardiac tissue engineering (CTE). However, some crucial issues should primarily be addressed before curcumin could be widely used in CTE. Expert opinion: The challenges regarding the use of curcumin in CTE include the optimum dosages of curcumin for promoting cardiac regeneration, the type of carrier used (e.g., polymeric matrices), the preferable release profile, as well as the short- and long-term toxicity in the human body.

The title of this article could sound a bit curious to some readers since a layer of apatite - and not calcium carbonate - is well-known to form on the surface of bioactive glasses upon immersion in simulated body fluids. However, calcium carbonate (commonly reported as calcite crystals) can form on the surface of bioactive glasses as well, instead of or in competition with hydroxyapatite, during in vitro tests. Major factors that govern calcium carbonate formation are a high concentration of Ca2+ ions in the testing solution - and, in this regard, glass composition/texture and type of medium play key roles - along with the volume of solution used during in vitro tests. To date, this phenomenon has received relatively little attention and is still partly unexplored. This article provides a critical overview of the available literature on this topic in order to stimulate constructive discussion among biomaterials scientists and further research for better understanding the mechanisms involved in glass bioactivity. STATEMENT OF SIGNIFICANCE: A literature search indicates that a layer of apatite - and not calcium carbonate - is well known to form on the surface of biomaterials during the bioactivity assessment. However, calcium carbonate can form on the surface as well, instead of or in competition with apatite. To date, this phenomenon has received relatively little attention and is still partly unexplored. This review provides a critical overview of the available literature on this topic in order to stimulate constructive discussions that can be further useful for clinical success.

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 SiO2–P2O5–CaO–MgO–Na2O–K2O 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.

Radiopacity is sometimes an essential characteristic of biomaterials that can help clinicians perform follow-ups during pre- and post-interventional radiological imaging. Due to their chemical composition and structure, most bioceramics are inherently radiopaque but can still be doped/mixed with radiopacifiers to increase their visualization during or after medical procedures. The radiopacifiers are frequently heavy elements of the periodic table, such as Bi, Zr, Sr, Ba, Ta, Zn, Y, etc., or their relevant compounds that can confer enhanced radiopacity. Radiopaque bioceramics are also intriguing additives for biopolymers and hybrids, which are extensively researched and developed nowadays for various biomedical setups. The present work aims to provide an overview of radiopaque bioceramics, specifically crystalline, non-crystalline (glassy), and nanostructured bioceramics designed for applications in orthopedics, dentistry, and cancer therapy. Furthermore, the modification of the chemical, physical, and biological properties of parent ceramics/biopolymers due to the addition of radiopacifiers is critically discussed. We also point out future research lacunas in this exciting field that bioceramists can explore further.

Head and neck cancer (HNC) is a category of cancers that typically arise from the nose-, mouth-, and throat-lining squamous cells. The later stage of HNC diagnosis significantly affects the patient’s survival rate. This makes it mandatory to diagnose this cancer with a suitable biomarker and imaging techniques at the earlier stages of growth. There are limitations to traditional technologies for early detection of HNC. Furthermore, the use of nanocarriers for delivering chemo-, radio-, and phototherapeutic drugs represents a promising approach for improving the outcome of HNC treatments. Several studies with nanostructures focus on the development of a targeted and sustained release of anticancer molecules with reduced side effects. Besides, nanovehicles could allow co-delivering of anticancer drugs for synergistic activity to counteract chemo- or radioresistance. Additionally, a new generation of smart nanomaterials with stimuli-responsive properties have been developed to distinguish between unique tumor conditions and healthy tissue. In this light, the present article reviews the mechanisms used by different nanostructures (metallic and metal oxide nanoparticles, polymeric nanoparticles, quantum dots, liposomes, nanomicelles, etc.) to improve cancer diagnosis and treatment, provides an up-to-date picture of the state of the art in this field, and highlights the major challenges for future improvements.

In this study, the biosynthesis of zinc oxide nanoparticles using Aspergillus niger (A/ZnO-NPs) is described. These particles have been characterized by UV–Vis spectrum analysis, X-ray powder diffraction, field emission scanning electron microscopy, and transmission electron microscopy. To use this biosynthesized nanoparticle as an antiproliferative and antimicrobial agent, the IC50 value against the breast cancer cell line and inhibition zone against Escherichia coli were used to optimize the effect of two processing factors including dose of filtrate fungi cell and temperature. The biosynthesized A/ZnO-NPs had an absorbance band at 320 nm and spherical shapes. The mean particles size was 35 nm. RSM (response surface methodology) was utilized to investigate the outcome responses. The Model F-value of 12.21 and 7.29 implies that the model was significant for both responses. The contour plot against inhibition zone for temperature and dose showed that if the dose increases from 3.8 to 17.2 µg/mL, the inhibition zone increases up to 35 mm. As an alternative to chemical and/or physical methods, biosynthesizing zinc oxide NPs through fungi extracts can serve as a more facile and eco-friendly strategy. Additionally, for optimization of the processes, the outcome responses in the biomedical available test can be used in the synthesis of ZnO-NPs that are utilized for large-scale production in various medical applications.

Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia.

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers’ interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.

The invention of bioactive glasses has undoubtedly represented an important watershed in the history of biomedicine, innovatively revolutionizing the key concept of biomaterials. Although 50 years have passed since the first bioactive glass (45S5 Bioglass®), these materials still continue to inspire numerous generations of researchers all over the world, attracted by the promise of numerous possible fields of investigations given by the versatility of glass manufacturing and processing strategies. This allows obtaining final clinical products that are incredibly diverse in terms of chemical characteristics, shape and texture and, therefore, adaptable to different therapeutic needs. The possibility to tune textural properties and degradation rates, perform high-temperature sintering processes without or minimally altering the original properties of the glass, as well as the facile introduction of therapeutically active ions within the composition and the easy surface functionalization led, over year, to the development of multiple pruducts to be used in various clinical fields, including the regeneration of both hard and soft tissues, bacterial/viral infection treatments and development of antitumoral strategies. This chapter opens a wide window on the world of bioactive glasses, starting with the description of their peculiar chemical properties, discussed in relation to the most commonly used manufacturing processes to obtain glass monoliths or particles. Then, an overview on the most common applications of BG-based products will be provided, paying particular attention to porous scaffolds for bone tissue engineering, bioactive coatings, antibacterial glasses and surface functionalization. In conclusion, a comprehensive overview on clinical applications updated to the state of the art will be provided.

Proper microstructural and transport properties are fundamental requirements for a suitable scaffold design and realization in tissue engineering applications. Scaffold microstructure (i.e. pore size, shape and distribution) and transport properties (i.e. intrinsic permeability), are commonly recognized as the key parameters related to the biological performance, such as cell attachment, penetration depth and tissue vascularization. While pore characteristics are relatively easy to asses, accurate and reliable evaluation of permeability still remains a challenge. In the present study, the microstructural properties of foam-replicated bioactive glass-derived scaffolds (basic composition 47.5SiO2–2.5P2O5–20CaO–10MgO–10Na2O–10K2O mol.%) were determined as function of the sintering temperature within the range 600-850°C, identified on the basis of thermal analyses that were previously performed on the material. Scaffolds with total porosity between 55 and 84 vol.% and trabecular-like architecture were obtained, with pore morphological features varying according to the sintering temperature. Mathematical modelling, supported by micro-computed tomography (μ-CT) imaging, was implemented to selectively investigate the effect of different pore features on intrinsic permeability, which was determined by laminar airflow alternating pressure wave drop measurements and found to be within 0.051-2.811·10−10 m2. The calculated effective porosity of the scaffolds was in the range of 46 to 66 vol.%, while the average pore diameter assessed by μ-CT varied between 220 and 780 μm, where the values in the lower range were observed for higher sintering temperatures (750-850°C). Experimental results were critically discussed by means of a robust statistical analysis. Finally, the complete microstructural characterization of the scaffolds was achieved by applying the general constitutive equation based on Forchheimer's theory.

The development of effective strategies for local administration of chemotherapeutic drugs, thus minimizing the adverse side effects to patients, is one of the key challenges in biomedicine and cancer research. This work reports the formulation and characterization of PluronicF127 microemulsions to enhance the bioavailability of Cisplatin (Cis). The size of Cis microemulsion was about 12.0 nm, as assessed by dynamic light scattering analysis. In vitro cytotoxic activity of free Cis and F127/Cis microemulsions were studied on malignant (C152 and MCF7) and normal (HUVEC) cells via tetrazolium (MTT) colorimetric assay. Cell morphology was also monitored. In vitro assessments revealed thatF127/Cis microemulsions induced cytotoxicity/morphological changes to a lesser extent than free Cis. Regarding in vivo experiments, F127/Cis microemulsions were injected intraperitoneally at 7 and 14 mg/kg doses into adult male Wistar rats to assess histologic and biochemical changes. In this case, the bulk Cis group caused severe histopathological changes and significant increases in serum liver enzymes and serum kidney function markers. The group treated with the 14 mg/kg dose of F127/Cis microemulsions also showed severe fatty changes and significant increases in serum liver enzymes, blood urea nitrogen, and creatinine levels. The group treated with the low dose of nano-Cis showed a significant increase in serum liver enzymes levels accompanied by mild fatty changes of the liver. Theoretical surveys were performed to get an understanding of the interplay between F127 and Cis. Results reveal that hydrogen bonding (HB) interactions with F127have an influence on the molecular properties of Cis and may playa role in the lower toxicity of F127/Cis in comparison to free Cis.

Bone fractures are in need of rapid fixation methods, but the current strategies are limited to metal pins and screws, which necessitate secondary surgeries upon removal. New techniques are sought to avoid surgical revisions, while maintaining or improving the fixation speed. Herein, a method of bone fixation is proposed with transparent biopolymers anchored in place via light-activated biocomposites based on expanding CaproGlu bioadhesives. The transparent biopolymers serve as a UV light guide for the activation of CaproGlu biocomposites, which results in evolution of molecular nitrogen (from diazirine photolysis), simultaneously expanding the covalently cross-linked matrix. Osseointegration additives of hydroxyapatite or Bioglass 45S5 yield a biocomposite matrix with increased stiffness and pullout strength. The structure-property relationships of UV joules dose, pin diameter, and biocomposite additives are assessed with respect to the apparent viscosity, shear modulus, spatiotemporal pin curing, and lap-shear adhesion. Finally, a model system is proposed based on ex vivo investigation with bone tissue for the exploration and optimization of UV-active transparent biopolymer fixation. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Accepted version Ministry of Education Tier 1 Grant RG17/18 (S): Novel light activated, diazo protecting groups, Ministry of Education Tier 2 Grant (MOE2018-T2-2-114): CaproGlu, Double sided wettissue adhesives, NTUitive POC (Gap) Fund NGF/2018/05: Aesthetic Applications of CaproGlu Bioadhesives, and A*Star IAF PP Grant (H19/01/a0/0II9): CathoGlu Bioadhesivespreventing catheter extravasation and skin infections.

Several biocompatible materials have been applied for managing soft tissue lesions; cerium oxide nanoparticles (CNPs, or nanoceria) are among the most promising candidates due to their outstanding properties, including antioxidant, anti-inflammatory, antibacterial, and angiogenic activities. Much attention should be paid to the physical properties of nanoceria, since most of its biological characteristics are directly determined by some of these relevant parameters, including the particle size and shape. Nanoceria, either in bare or functionalized forms, showed the excellent capability of accelerating the healing process of both acute and chronic wounds. The skin, heart, nervous system, and ophthalmic tissues are the main targets of nanoceria-based therapies, and the other soft tissues may also be evaluated in upcoming experimental studies. For the repair and regeneration of soft tissue damage and defects, nanoceria-incorporated film, hydrogel, and nanofibrous scaffolds have been proven to be highly suitable replacements with satisfactory outcomes. Still, some concerns have remained regarding the long-term effects of nanoceria administration for human tissues and organs, such as its clearance from the vital organs. Moreover, looking at the future, it seems necessary to design and develop three-dimensional (3D) printed scaffolds containing nanoceria for possible use in the concepts of personalized medicine.

Although the three main phases of iron oxide – hematite, maghemite, and magnetite – exhibit superparamagnetic properties at the nanoscale, only maghemite and magnetite phases have been explored in magnetic bioactive glass-ceramics aimed at applications in cancer treatment by hyperthermia. In this work, it is reported for the first time the superparamagnetic properties of hematite nanocrystals grown in a 58S bioactive glass matrix derived from sol-gel synthesis. The glass-ceramics are based on the (100-x)(58SiO2-33CaO-9P2O5)-xFe2O3 system (x = 10, 20 and 30 wt%). A thermal treatment leads to the growth of hematite (α-Fe2O3) nanocrystals, conferring superparamagnetic properties to the glass-ceramics, which is enough to produce heat under an external alternating magnetic field. Besides, the crystallization does not inhibit materials bioactivity, evidenced by the formation of calcium phosphate onto the glass-ceramic surface upon soaking in simulated body fluid. Moreover, their cytotoxicity is similar to other magnetic bioactive glass-ceramics reported in the literature. Finally, these results suggest that hematite nanocrystals' superparamagnetic properties may be explored in multifunctional glass-ceramics applied in bone cancer treatment by hyperthermia allied to bone regeneration.

Tissue engineering provides great possibilities to manage tissue damages and injuries in modern medicine. The involvement of hard biocompatible materials in tissue engineering-based therapies for the healing of soft tissue defects has impressively increased over the last few years: in this regard, different types of bioceramics were developed, examined and applied either alone or in combination with polymers to produce composites. Bioactive glasses, carbon nanostructures, and hydroxyapatite nanoparticles are among the most widely-proposed hard materials for treating a broad range of soft tissue damages, from acute and chronic skin wounds to complex injuries of nervous and cardiopulmonary systems. Although being originally developed for use in contact with bone, these substances were also shown to offer excellent key features for repair and regeneration of wounds and "delicate" structures of the body, including improved cell proliferation and differentiation, enhanced angiogenesis, and antibacterial/anti-inflammatory activities. Furthermore, when embedded in a soft matrix, these hard materials can improve the mechanical properties of the implant. They could be applied in various forms and formulations such as fine powders, granules, and micro- or nanofibers. There are some pre-clinical trials in which bioceramics are being utilized for skin wounds; however, some crucial questions should still be addressed before the extensive and safe use of bioceramics in soft tissue healing. For example, defining optimal formulations, dosages, and administration routes remain to be fixed and summarized as standard guidelines in the clinic. This review paper aims at providing a comprehensive picture of the use and potential of bioceramics in treatment, reconstruction, and preservation of soft tissues (skin, cardiovascular and pulmonary systems, peripheral nervous system, gastrointestinal tract, skeletal muscles, and ophthalmic tissues) and critically discusses their pros and cons (e.g., the risk of calcification and ectopic bone formation as well as the local and systemic toxicity) in this regard. STATEMENT OF SIGNIFICANCE: Soft tissues form a big part of the human body and play vital roles in maintaining both structure and function of various organs; however, optimal repair and regeneration of injured soft tissues (e.g., skin, peripheral nerve) still remain a grand challenge in biomedicine. Although polymers were extensively applied to restore the lost or injured soft tissues, the use of bioceramics has the potential to provides new opportunities which are still partially unexplored or at the very beginning. This reviews summarizes the state of the art of bioceramics in this field, highlighting the latest evolutions and the new horizons that can be opened by their use in the context of soft tissue engineering. Existing results and future challenges are discussed in order to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers of the biomaterials community.

Mesoporous bioactive glasses (MBGs) offer suitable platforms for drug/ion delivery in tissue engineering strategies. The main goal of this study was to prepare strontium (Sr)- and cobalt (Co)-doped MBGs, strontium is currently used in the treatment of osteoporosis, and cobalt is known to exhibit pro-angiogenic effects. Sr- and Co-doped mesoporous glasses were synthesized for the first time in a multicomponent silicate system via the sol&ndash, gel method by using P123 as a structure-directing agent. The glassy state of the Sr- and Co-doped materials was confirmed by XRD before immersion in SBF, while an apatite-like layer was detected onto the surface of samples post-immersion. The textural characteristics of MBGs were confirmed by nitrogen adsorption/desorption measurements. In vitro experiments including MTT assay, Alizarin red staining, and cell attachment and migration showed the cytocompatibility of all the samples as well as their positive effects on osteoblast-like cell line MG-63. Early experiments with human umbilical vein endothelial cells also suggested the potential of these MBGs in the context of angiogenesis. In conclusion, the prepared materials were bioactive, showed the ability to improve osteoblast cell function in vitro and could be considered as valuable delivery vehicles for therapeutics, like Co2+ and Sr2+ ions.

Bioactive glass coatings were deposited for the first time onto wood-derived biocarbon scaffolds using the sol-gel technique. The cellular pore structure of the beech wood was retained during the sol-gel coating process. Owing to the presence of the bioactive glass layer, the originally bioinert biocarbon scaffold was fully covered with newly-formed hydroxyapatite (HA) upon soaking in simulated body fluid. The ability to form HA is generally accepted as the proof of in vitro bioactivity. This opens up the possible application of wood-derived scaffolds in biomedicine (bone repair) and biotechnology.

The control of bacterial infections is of particular importance in the field of tissue engineering. Recently, much attention has been addressed toward the use of mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily because of their capability of acting as carriers for the local release of antimicrobial agents. The incorporation of antibacterial metallic ions including silver (Ag+), zinc (Zn2+), copper (Cu+ and Cu2+), cerium (Ce3+ and Ce4+), and gallium (Ga3+) cations into the MBG structure and their controlled release is proposed as one of the most attractive strategies for inhibiting bacterial growth and reproduction. Moreover, the possibility of loading and delivering various antibacterial biomolecules (e.g., antibiotics) through the porous structure of MBGs makes them as ideal candidates for antibacterial applications. In this review, we aim to present a comprehensive evaluation of MBG potential regarding antibacterial activities. For this purpose, different types of antibacterial ion-doped and drug-loaded MBGs are introduced and discussed in the light of existing knowledge, along with the significant challenges ahead. Statement of significance Prevention and treatment of infections is one of the today’s greatest challenges in medical sciences, also considering the well-known issues related to increased bacterial resistance to antibiotics. The advent of mesoporous glasses led to the birth of a new class of multifunctional biomaterials acting as bioactive platforms for the local release of organic or inorganic agents eliciting an antimicrobial effect. This reviews summarizes the state of the art of MBGs in this field, highlighting the latest evolutions and the specific role played by metallic antimicrobial ions that can be incorporated in the glass composition and then properly released. Perspective for tissue engineering applications are also discussed to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers.

A copper oxide/cerium oxide nanocomposite (CuO/CeO2, NC) was synthesized via a novel method using a metal–organic framework as a precursor. This nanomaterial was characterized by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic light scattering size analysis (DLS), and zeta potential. The PXRD showed the successful synthesis of the CuO/CeO2 NC, in which the 2theta values of 35.55° (d = 2.52 Å, 100%) and 38.73° (d = 2.32 Å, 96%) revealed the existence of copper (II) oxide. FTIR analysis showed the CeO2, hydroxyl groups, absorbed water, and some residual peaks. The solid phase analysis by FESEM and TEM images showed mean particle sizes of 49.18 ± 24.50 nm and 30.58 ± 26.40 nm, respectively, which were comparable with crystallite size (38.4 nm) obtained from PXRD, but it appears the CuO/CeO2 NC was not evenly distributed and in some areas, showed it was highly agglomerated. The hydrodynamic size (750.5 nm) also showed the agglomeration of the CuO/CeO2 NCs in the solution, which had a negatively charged surface. The CuO/CeO2 NCs showed anti-proliferative activity against human breast cancer cell line (MCF-7) in a dose- and time-dependence way, while affecting normal cells less significantly.

Bioactive sol-gel glasses are attractive biomaterials from both technological and functional viewpoints as they require lower processing temperatures compared to their melt-derived counterparts and exhibit a high specific surface area due to inherent nanoporosity. However, most of these materials are based on relatively simple binary or ternary oxide systems since the synthesis of multicomponent glasses via sol-gel still is a challenge. This work reports for the first time the production and characterization of sol-gel materials based on a six-oxide basic system (SiO2&ndash, P2O5&ndash, CaO&ndash, MgO&ndash, Na2O&ndash, K2O). It was shown that calcination played a role in inducing the formation of crystalline phases, thus generating glass-ceramic materials. The thermal, microstructural and textural properties, as well as the in vitro bioactivity, of these sol-gel materials were assessed and compared to those of the melt-derived counterpart glass with the same nominal composition. In spite of their glass-ceramic nature, these materials retained an excellent apatite-forming ability, which is key in bone repair applications.

The advent of mesoporous bioactive glasses (MBGs) in applied bio-sciences led to the birth of a new class of nanostructured materials combining triple functionality, that is, bone-bonding capability, drug delivery and therapeutic ion release. However, the development of hierarchical three-dimensional (3D) scaffolds based on MBGs may be difficult due to some inherent drawbacks of MBGs (e.g., high brittleness) and technological challenges related to their fabrication in a multiscale porous form. For example, MBG-based scaffolds produced by conventional porogen-assisted methods exhibit a very low mechanical strength, making them unsuitable for clinical applications. The application of additive manufacturing techniques significantly improved the processing of these materials, making it easier preserving the textural and functional properties of MBGs and allowing stronger scaffolds to be produced. This review provides an overview of the major aspects relevant to 3D printing of MBGs, including technological issues and potential applications of final products in medicine.

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The use of three-dimensional (3D) scaffolds is recognized worldwide as a valuable biomedical approach for promoting tissue regeneration in critical-size bone defects. Over the last 50 years, bioactive glasses have been intensively investigated in a wide range of different clinical applications, from orthopedics to soft tissue healing. Bioactive glasses exhibit the unique capability to chemically bond to the host tissue and, furthermore, their processing versatility makes them very appealing due to the availability of different manufacturing techniques for the production of porous and interconnected synthetic bone grafts able to support new tissue growth over the whole duration of the treatment. As a novel contribution to the broad field of scaffold manufacturing, we report here an effective and relatively easy method to produce silicate glass-derived scaffolds by using, for the first time in the biomedical field, dolomite powder as a foaming agent for the formation of 3D bone-like porous structures. Morphological/structural features, crystallization behavior, and in vitro bioactivity in a simulated body fluid (SBF) were investigated. All the tested scaffolds were found to fulfil the minimum requirements that a scaffold for osseous repair should exhibit, including porosity (65&ndash, 83 vol.%) and compressive strength (1.3&ndash, 3.9 MPa) comparable to those of cancellous bone, as well as hydroxyapatite-forming ability (bioactivity). This study proves the suitability of a dolomite-foaming method for the production of potentially suitable bone grafts based on bioactive glass systems.

Bioactive glasses (BGs) have been identified as highly versatile materials in tissue engineering applications; apart from being used for bone repair for many years, they have recently shown promise for the regeneration of peripheral nerves as well. They can be formulated in different shapes and forms (micro-/nanoparticles, micro-/nanofibers, and tubes), thus potentially meeting the diverse requirements for neuroregeneration. Mechanical and biological improvements in three-dimensional (3D) polymeric scaffolds could be easily provided by adding BGs to their composition. Various types of silicate, borate, and phosphate BGs have been examined for use in neuroregeneration. In general, BGs show good compatibility with the nervous system compartments both in vitro and in vivo. Functionalization and surface modification plus doping with therapeutic ions make BGs even more effective in peripheral nerve regeneration. Moreover, the combination of BGs with conductive polymers is suggested to improve neural cell functions at injured sites. Taking advantage of BGs combined with novel technologies in tissue engineering, like 3D printing, can open new horizons in reconstructive approaches for the nervous system. Although there are great potential opportunities in BG-based therapies for peripheral nerve regeneration, more research should still be performed to carefully assess the pros and cons of BGs in neuroregeneration strategies.

Copper is one of the most used therapeutic metallic elements in biomedicine, ranging from antibacterial approaches to cancer theranostics. This element could be easily incorporated into different types of biomaterials; specifically, copper-doped bioactive glasses (BGs) provide great opportunities for biomedical engineers and clinicians as regards their excellent biocompatibility and regenerative potential. Although copper-incorporated BGs are mostly used in bone tissue engineering, accelerated soft tissue healing is achievable, too, with interesting potentials in wound treatment and skin repair. Copper can modulate the physico-chemical properties of BGs (e.g., reactivity with bio-fluids) and improve their therapeutic potential. Improving cell proliferation, promoting angiogenesis, reducing or even prohibiting bacterial growth are counted as prominent biological features of copper-doped BGs. Recent studies have also suggested the suitability of copper-doped BGs in cancer photothermal therapy (PTT). However, more research is needed to determine the extent to which copper-doped BGs are actually applicable for tissue engineering and regenerative medicine strategies in the clinic. Moreover, copper-doped BGs in combination with polymers may be considered in the future to produce relatively soft, pliable composites and printable inks for use in biofabrication.

The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained. This goal is achieved using bone graft materials, which should simulate extracellular matrix (ECM), in order to promote osteoblast proliferation and fill the void, maintaining the space without collapsing until the new bone is formed. In this work, we design, develop and characterize a novel, moldable chitosan-pectin hydrogel reinforced by biphasic calcium phosphate particles with size in the range of 100–300 μm. The polysaccharide nature of the hydrogel mimics the ECM of natural bone, and the ceramic particles promote high osteoblast proliferation, assessed by Scanning Electron Microscopy analysis. Swelling properties allow significant adsorption of water solution (up to 200% of solution content) so that the bone defect space can be filled by the material in an in vivo scenario. The incorporation of ceramic particles makes the material stable at different pH and increases the compressive elastic modulus, toughness and ultimate tensile strength. Furthermore, cell studies with SAOS-2 human osteoblastic cell line show high cell proliferation and adhesion already after 72 h, and the presence of ceramic particles increases the expression of alkaline phosphatase activity after 1 week. These results suggest a great potential of the developed moldable biomaterials for the regeneration of the alveolar bone. Statement of Significance The positive fate of a surgical procedure involving the insertion of a titanium screw still depends on the quality and quantity of alveolar bone which is present in the extraction site. Available materials are basically hard scaffold materials with un-predictable behavior in different condition and difficult shaping properties. In this work we developed a novel pectin-chitosan hydrogel reinforced with ceramic particles. Polysaccharides simulate the extracellular matrix of natural bone and the extensive in vitro cells culture study allows to assess that the incorporation of the ceramic particles promote a pro-osteogenic response. Shape control, easy adaption of the extraction site, predictable behavior in different environment condition, swelling properties and an anti-inflammatory response are the significant characteristics of the developed biomaterial.

Background One of the hardest tasks in developing or selecting grafts for bone substitution surgery or tissue engineering is to match the structural and mechanical properties of tissue at the recipient site, because of the large variability of tissue properties with anatomical site, sex, age and health conditions of the patient undergoing implantation. We investigated the feasibility of defining a quantitative bone structural similarity score based on differences in the structural properties of synthetic grafts and bone tissue. Methods Two biocompatible hydroxyapatite porous scaffolds with different nominal pore sizes were compared with trabecular bone tissues from equine humerus and femur. Images of samples’ structures were acquired by high-resolution micro-computed tomography and analyzed to estimate porosity, pore size distribution and interconnectivity, specific surface area, connectivity density and degree of anisotropy. Young's modulus and stress at break were measured by compression tests. Structural similarity distances between sample pairs were defined based on scaled and weighted differences of the measured properties. Their feasibility was investigated for scoring structural similarity between considered scaffolds or bone tissues. Results Manhattan distances and Quadrance generally showed sound and consistent similarities between sample pairs, more clearly than simple statistical comparison and with discriminating capacity similar to image-based scores to assess progression of pathologies affecting bone structure. Conclusions The results suggest that a quantitative and objective bone structural similarity score may be defined to help biomaterials scientists fabricate, and surgeons select, the graft or scaffold best mimicking the structure of a given bone tissue.

Discouraging bacterial colonization of ocular biomaterials and implants is a significant challenge in ophthalmology as infections often lead to the need for secondary surgery, with associated risks and additional stress to patients. In this work we demonstrate for the first time the feasibility of an innovative antibacterial ocular prosthesis produced by depositing a silver nanocluster/silica composite layer on the poly(methyl methacrylate) implant surface via radio-frequency sputtering. Tape test performed according to relevant ASTM standard provided a preliminary evidence of the mechanical stability and good adhesion of the coating to the substrate (absence of macroscopic damage after tape removal). Coating integrity was maintained after prolonged soaking in aqueous medium (1 month). The antibacterial effect of the coating, associated to silver ion release upon contact with aqueous fluid, was confirmed by the in vitro formation of a 5-mm inhibition halo test against Staphylococcus aureus that is one of the most common bacteria involved in ocular infections. The approach proposed in the present study for facing implant-related ocular infections can have a significant impact in the field of ophthalmic biomaterials, suggesting a valuable alternative to the administration of antibiotics that may become ineffective due to bacterial resistance.

Multifunctional scaffolds were prepared by foaming Fe-containing sols according to a composition-optimized approach. These foams exhibited high specific surface area (16–80 m2/g) and hierarchical porosity from the macro- (50–600 µm) to the meso-scale (4–20 nm). The effects of iron content on the textural properties and in vitro bioactivity were investigated. It was observed that the increase of iron content involved a decrease of specific surface and mesopore size. Interestingly, an excellent apatite-forming ability was observed regardless of the material composition. The potential osteoconductivity of these bioactive foams, coupled with their ferrimagnetic properties, open new perspectives as regards the hyperthermia-assisted treatment and regeneration of osseous defects caused by bone cancer.

Over the last decade, there has been an impressive growth of new potential applications for bioactive glasses (BGs) in regenerative medicine. Apart from being used in contact with injured bone, BGs are now showing promise in accelerating the healing of soft tissues too, such as epithelium, thus creating new hopes for the repair of damaged skin, gastrointestinal tract and airspaces of the lungs. BGs can form a biological bond with soft tissues, accelerate epithelial cell proliferation, and reduce the inflammation in the injured sites. BGs can also be added to "soft" polymeric matrices for imparting biological extra-functionalities (e.g. enhanced angiogenesis) which play a key role in epithelial reconstruction strategies. The aim of this study is to provide a critical review of the potential of various types of BGs for the repair and regeneration of the epithelial tissues based on the existing data in the literature.

Implementing novel approaches for cancer therapy are under continuous progress, and bioactive glasses (BGs) and glass-ceramics show excellent potential in this regard. Although these materials have been mostly used as magnetic substances in hyperthermia approach, some of their subsets, i.e., mesoporous bioactive glasses (MBGs), have been recently proposed not only as magnetic materials but also as drug delivery systems for advanced treatment of bone cancer. Different types of MBGs including granular particles and three-dimensional (3D) scaffolds can be applied for cancer therapy. Based on the results obtained from in vitro studies, MBGs seem to have a bright future in the therapeutic strategies to combat cancer; however, their application in this field is still in its beginning, and more research needs to reveal all pros and cons of this newly proposed approach.