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Electrospinning is a promising approach for the development of fibrous tissue engineering (TE) scaffolds suitable for hard and soft tissues. Apart from physicomechanical properties, electrospun fibers are required to incorporate bioactive cues to control cellular functions, including facilitating biomineralization and osteogenic differentiation in case of bone TE, as well as vascularization, to support successful tissue regeneration. In recent years, bioactive glass (BG) addition to electrospun biopolymer fibers has shown promising results in enhancing the properties of fibers, including the improvement of biological performance. In this article, a comprehensive overview of BG‐containing electrospun polymer composite fibers is presented, identifying the parameters that affect the mechanical properties as well as the biological response in vivo and in vitro. Subsequently, the effects of BG addition on the properties of the scaffolds are discussed. Recent developments in the fields of bone regeneration, wound healing, and drug delivery using BG‐containing electrospun fibrous scaffolds are described in detail. Essential aspects related to BG‐polymer composite fibers for translational research in TE are highlighted for future research in this field.

A number of electrically conducting polymers, such as polyaniline (PANi), as well as functionalized aniline copolymers and composites, which are simultaneously biodegradable and conductive, have been applied for developing electrically conductive scaffolds for tissue engineering (TE) in recent years. The rationale behind these scaffolds is to induce ‘electroactivity’ in scaffolds, as many research works have shown that an intrinsic electrical activity leads to both increased regeneration rates and improved healing of damaged tissues. PANi is the conductive polymer of choice because it is economical and easy to process with a variety of methods. The resultant PANi based biomaterials have shown biocompatibility, conductivity, suitable processability, positive cellular response, as well as an intrinsic antibacterial effect in numerous research studies. The analysis of the literature has revealed that PANi based scaffolds have been investigated for TE applications including skin/wound healing, bone, cartilage, nerve/spinal cord, vascular, skeletal muscle repair and for the treatment of infertility. Although PANi based materials find widespread applications in other sectors, they are still far away from being commercially exploited as scaffolds for TE despite positive research results. This review aims to discuss and critically assess the current state of PANi based TE scaffolds for different applications. A future perspective for utilizing PANi based biomaterials for applications in TE is discussed, including recent considerations about potential cytotoxic effects.

Correction for ‘45S5 bioactive glass-based scaffolds coated with cellulose nanowhiskers for bone tissue engineering’ by Wei Li et al., RSC Adv., 2014, 4, 56156–56164, https://doi.org/10.1039/C4RA07740G.

Gelatin-coated, 3D sponge-like scaffolds based on 45S5 bioactive glass were produced using the foam replication technique. Compressive strength tests of gelatin-coated samples compared to uncoated scaffolds showed significant strengthening and toughening effects of the gelatin coating with compressive strength values in the range of cortical bone. Additionally, the crosslinked gelatin network (using either caffeic acid or N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC)/N-hxdroxysuccinimide (NHS) as crosslinking agent) was shown to be a suitable candidate for the sustained release of the bioactive molecule icariin. Concerning bioactivity of the produced scaffolds, characterization by FTIR and SEM indicated the formation of hydroxyapatite (HA) in all samples after immersion in simulated body fluid (SBF) for 14 days, highlighting the favorable combination of mechanical robustness, bioactivity and drug delivery capability of this new type of scaffolds., Graphical abstract Image 1, Highlights • Foam like bioactive glass scaffolds produced by replication technique. • Gelatin coatings confer increased compression strength to scaffolds. • Crosslinked gelatin coating is suitable candidate for the sustained release of icariin. • Favorable combination of bioactivity, gelatin coating and icariin release demonstrated.

We investigated the bioactivity and cytocompatibility of 45S5 bioactive glass (BG) based scaffolds coated with a composite layer formed by gelatin and manganese doped mesoporous bioactive glass nanoparticles (Mn-MBGNs). The scaffolds were prepared using the foam replica method, and they were further coated with Mn-MBGNs/gelatin via dip coating. The synthesized scaffolds were characterized in relation to morphology, porosity, mechanical stability, bioactivity and cell biology behavior using osteoblast-like (MG-63) cells. The scaffolds were highly porous with interconnected porosity, and a suitable pore structure was maintained even after the Mn-MBGNs/gelatin coating. Energy-dispersive X-ray spectroscopy (EDX) confirmed the presence of Mn-MBGNs in the coatings. Moreover, the presence of gelatin was confirmed by Fourier transform infrared spectroscopy (FTIR). The coated scaffolds exhibited in-vitro bioactivity in simulated body fluid comparable to that of uncoated BG scaffolds. Finally, Mn-MBGNs/gelatin coated scaffolds were shown to be non-cytotoxic to MG-63 cells. Hence, the results presented here confirm that the novel Mn containing scaffolds can be considered in the field of biologically active ion releasing scaffolds for bone tissue engineering applications.

Geopolymers continue to attract interest owing to their good mechanical properties in combination with the ecofriendly fabrication process. However, the applications of geopolymers are still restricted to a limited field, mainly as construction materials. Designing and fabricating components of complex, intricate shape for applications beyond building materials may represent a useful approach to broaden geopolymer applications. In this study, unconventional processing and finishing technologies, such as direct ink printing, drilling, and machining are investigated to demonstrate their suitability for geopolymers. Fly ash-based geopolymers incorporating a relevant amount of waste glass demonstrated suitable flow properties to be used in a direct ink printing process. Moreover, the geopolymer specimens showed high machinability: components were drilled and machined in a lathe obtaining superior surface finish, uniform dimensional accuracy, and complex shape parts. The results presented herein indicate opportunities for expanding applications of geopolymers in areas such as mechanical engineering, where components with accurate, specifically designed shapes and surface finish are needed.

Geopolymers continue to attract interest owing to their good mechanical properties in combination with the ecofriendly fabrication process. However, the applications of geopolymers are still restricted to a limited field, mainly as construction materials. Designing and fabricating components of complex, intricate shape for applications beyond building materials may represent a useful approach to broaden geopolymer applications. In this study, unconventional processing and finishing technologies, such as direct ink printing, drilling, and machining are investigated to demonstrate their suitability for geopolymers. Fly ash-based geopolymers incorporating a relevant amount of waste glass demonstrated suitable flow properties to be used in a direct ink printing process. Moreover, the geopolymer specimens showed high machinability: components were drilled and machined in a lathe obtaining superior surface finish, uniform dimensional accuracy, and complex shape parts. The results presented herein indicate opportunities for expanding applications of geopolymers in areas such as mechanical engineering, where components with accurate, specifically designed shapes and surface finish are needed.

Due to the limited regenerative capacity of the natural human myocardium, 3D printing of the cyclic polyester poly (glycerol sebacate) (PGS) offers a promising alternative to produce scaffolds (cardiac patches) for cardiac tissue engineering. Since the 3D printability and subsequent thermal crosslinking of pure PGS without any modification or additives are challenging, a PGS‐zein‐salt‐based printing process is developed in this work by mixing PGS pre‐polymer with ground and sieved sodium chloride particles and additionally with different amounts of the corn protein zein. The resulting inks show excellent printability and high shape fidelity both during the printing process and after thermal crosslinking. Chemical analysis indicates the successful integration of zein into the PGS backbone. Mechanical characterization shows the anisotropic behavior of the structure in the alternating printing direction. Subsequent biological assessments reveal no cytotoxic effects on C2C12 cells, rendering the developed PGS‐zein combination a suitable material for 3D printing of cardiac patches.

Natural marine sponges were used as sacrificial template for the fabrication of bioactive glass‐based scaffolds. After sintering at 1050°C, the resulting samples were additionally coated with a silicate solution containing biologically active ions (Ag and Ga), well‐known for their antibacterial properties. The produced scaffolds were characterized by superior mechanical properties (maximum compressive strength of 4 MPa) and total porosity of ~80% in comparison to standard scaffolds made by using PU foam templates. Direct cell culture tests performed on the uncoated and coated samples showed positive results in terms of adhesion, proliferation, and differentiation of MC3T3‐E1 cells. Moreover, vascular endothelial growth factor (VEGF) secretion from cells in contact with scaffold dissolution products was measured after 7 and 10 days of incubation, showing promising angiogenic results for bone tissue engineering applications. The antibacterial potential of the produced samples was assessed by performing agar diffusion tests against both Gram‐positive and Gram‐negative bacteria.

Composite biomaterials based on proteins and inorganic fillers are highly attractive for wound dressing applications due to their highly absorbent properties towards blood and exudate provided by the inorganic fillers. Moreover, such composites offer a desirable environment for cells due to the combination of organic and inorganic characteristics. This study highlights the fabrication of soy protein isolate/nanoscale bioactive glass composite films by solvent casting method as a matrix for wound-dressing applications. The effect of the addition of bioactive glass nano particles on blood clotting was assessed. Cytotoxicity and in vitro cytocompatibility of the films were also tested. The results showed that the composite films could meet the essential requirements for an appropriate wound dressing with additional favorable properties such as hemostatic capability and mechanical properties as well as significant cell cytocompatibility.

Hydrogels from natural polymers are widely used in tissue engineering due to their unique properties, especially when regarding the cell environment and their morphological similarity to the extracellular matrix (ECM) of native tissues. In this study, we describe the production and characterization of novel hybrid hydrogels composed of alginate blended with elastin from bovine neck ligament. The properties of elastin as a component of the native ECM were combined with the excellent chemical and mechanical stability as well as biocompatibility of alginate to produce two hybrid hydrogels geometries, namely 2D films obtained using sonication treatment and 3D microcapsules produced by pressure-driven extrusion. The resulting blend hydrogels were submitted to an extensive physico-chemical characterization. Furthermore, the biological compatibility of these materials was assessed using normal human dermal fibroblasts, indicating the suitability of this blend for soft tissue engineering.

45S5 bioactive glass (BG) scaffolds show great potential in bone tissue engineering due to their superior osteoinductivity and osteoconductivity. However, such scaffolds generally possess poor mechanical properties. Here, inspired by the reinforcing principle of confined concrete elements in civil engineering, poly caprolactone (PCL)/polyethylene glycol (PEG) film‐wrapped 45S5 BG scaffolds were prepared by gluing highly porous foam–replicated BG scaffolds and electrospun PCL/PEG films together with a PCL layer. The results showed that the compressive strength of the PCL/PEG film‐wrapped scaffolds was greatly improved, compared to that of unwrapped BG scaffolds. Moreover, the PCL/PEG film exhibited hydrophilicity, responsible for improved cell activity with respect to the hydrophobic PCL one. Thus, the present work introduces a convenient approach to improve the mechanical properties of highly porous bioceramic scaffolds, and is relevant for future robust scaffold design.

Electrophoretic deposition (EPD) was used to apply bioactive multifunctional composite coatings with antibacterial substances on stainless steel AISI 316L (SS). Tetracycline hydrochloride (TCN) loaded halloysite nanotubes were co-deposited with chitosan and bioactive glass (BG) particles to produce composite coatings. SEM/EDX, XRD, and FTIR analyses were performed to characterize the composition and microstructure of coatings. The release of tetracycline hydrochloride (TCN) in phosphate buffered saline (PBS) was investigated by UV spectrometry, and measurements indicated the release of around 54% of the drug within 14 days of immersion in PBS. Furthermore, to determine that the bioactivity of coatings had not been adversely influenced, simulated body fluid (SBF) bioactivity tests were performed. The formation of hydroxyl carbonate apatite on the surface of the coatings was confirmed after 3 days. The ability of coatings to prevent bacterial growth was tested using E . coli as gram-negative and S . aureus as gram-positive bacteria. Results showed improved bactericidal effect of TCN-containing coatings compared to non-TCN loaded coatings. The corresponding amount of TCN loaded in EPD coatings supported cell viability and proliferation of MG-63 cells for up to 3 days. Fluorescence images of MG-63 cells showed evidence of cell growth in islands on the coated surface. The surface roughness of the coating loaded with halloysite nanotubes supported cell adhesion and proliferation. Additionally, the wettability value of the coatings confirmed a moderately hydrophilic surface, which is suitable for bone regenerative applications. Improved corrosion resistance compared to the pure stainless steel (SS) substrate was confirmed. The adhesion between coatings and substrates was tested by the tape test, and the result showed sufficient adhesion of the coatings to be handled without detachment. In all, the new coating system has potential for applications in orthopedics.

Nano- and micro-scale topographical features play a critical role in the induction and maintenance of various cellular properties and functions, including morphology, adhesion, gene regulation, and cell-to-cell communication. In addition, recent studies have indicated that the structure and function of heart tissue are also sensitive to mechanical cues at the nano- and micro-scale. Although fabrication methods exist for generating topographical features on polymeric scaffolds for cell culture, current techniques, especially those with nano-scale resolution, are typically complex, prohibitively expensive and not accessible to most biology laboratories. Here, we present a simple and tunable fabrication method for the production of patterned electrospun fibers that simulate the complex anisotropic and multi-scale architecture of cardiac tissue, to promote cardiac cell alignment. This method is based on the combination of electrospinning and soft lithography techniques, in which electrospun fibers, based on a blend of poly(glycerol sebacate) and poly(caprolactone), were collected on a patterned Teflon-coated silicon wafer with imprinted topographical features. Different surface topographies were investigated, such as squares and grooves, with constant or different interspatial distances. In vitro cell culture studies successfully demonstrated the alignment of both C2C12 myoblasts and neonatal rat cardiomyocytes on fabricated electrospun patterned surfaces. C2C12 cells were cultured over a period of 72 h to study the effect of topographical cues on cell morphology. Cells attached within the first 8 h after seeding and after 24 h most of the cells started to align responding to the topographical cues. Similarly, cardiomyocytes responded to the topographical features by aligning themselves and by expressing Connexin 43 along cellular junctions. Summarizing, we have developed a new method with the potential to significantly promote cardiac tissue engineering by fabricating electrospun fibers with defined topographical features to guide and instruct donor and/or host cells.

Developments in the field of materials science are contributing to providing solutions for the recycling of industrial residues to develop new materials. Such approaches generate new products and provide optimal alternatives to the final disposal of different types of industrial wastes. This research focused on identifying and characterizing slag, fly ash, and glass cullet from the Boyac&aacute, region in Colombia as raw materials for producing glass-ceramics, with the innovative aspect of the use of these three residues without the addition of nucleating agents to produce the glass-ceramics. To characterize the starting materials, X-ray diffraction (XRD), X-ray fluorescence (XRF), and Scanning Electron Microscopy (SEM) techniques were used. The results were used to evaluate the best conditions to produce mixtures of the three waste components and to determine the specific compositions of glass-ceramics to achieve products with attractive technical properties for potential industrial applications. The proposed mixtures were based on three compositions: Mixture 1, 2, and 3. The materials were obtained through thermal treatment at 1200 &deg, C in a tubular furnace in accordance with the results of a comprehensive characterization using thermal analysis. The microstructure, thermal stability, and structural characteristics of the samples were examined through SEM, differential thermal analysis (DTA), and XRD analyses, which showed that the main crystalline phases were diopside and anorthite, with a small amount of enstatite and gehlenite. The obtained glass-ceramics showed properties of technical significance for structural applications.

Herbal medicine, the use of plants or plant extracts with known beneficial biological effects to treat and/or prevent diverse health disorders, has been known for thousands of years. After their replacement by synthetic drugs in the beginning of the 20th century, plant derived therapeutic agents have been recently attaining more attention again. Phytotherapeutics, which can be extracted from a wide range of different herbal plants, are believed to have a broad spectrum of therapeutic effects and less negative side effects than synthetic drugs. On the other hand, it is often difficult to prove the therapeutic effect of herbal drugs due to their chemical complexity. In the last decade, research has focused increasingly on the relatively new concept of the combination of herbal drugs with modern engineered biomaterials in order to achieve synergy of their therapeutic effects. Even if several studies based on this concept have been published, no systematic overview of the performed investigations and their results is available. In this context, this review focuses on the combination of phytotherapeutics with bioactive glasses (BGs), which are bioactive and biodegradable materials capable of releasing biologically active ions being suitable for several applications as bone substituting and replacing materials as well as in the regeneration of soft and hard tissue. The literature search was carried out using the WEB OF SCIENCE® and SCOPUS® databases using a combination of relevant keywords. Besides giving an overview of the research done in the last years and summarizing the results obtained in those studies, the possible synergistic effects of herbal drugs in combination with BGs are critically discussed, and potential health risks are overviewed. Of all plant-derived drugs investigated so far, the coumarin family appears to be the one that has been most widely combined with BGs showing beneficial outcomes. Overall, the analysis of the literature has revealed the great potential of this organic-inorganic multi-functional system approach as an advantageous alternative to conventional medicine in several applications, but also highlights the need for more systematic in vivo studies to evaluate the effective time and dose dependent combined effects of BGs and phytotherapeutic agents.

Electrospun organic/inorganic hybrid scaffolds have been appealing in tissue regeneration owing to the integrated physicochemical and biological performances. However, the conventional electrospun scaffolds with non-woven structures usually failed to enable deep cell infiltration due to the densely stacked layers among the fibers. Herein, through self-assembly-driven electrospinning, a polyhydroxybutyrate/poly(e-caprolactone)/58S sol-gel bioactive glass (PHB/PCL/58S) hybrid scaffold with honeycomb-like structures was prepared by manipulating the solution composition and concentration during a one-step electrospinning process. The mechanisms enabling the formation of self-assembled honeycomb-like structures were investigated through comparative studies using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) between PHB/PCL/58S and PHB/PCL/sol-gel silica systems. The obtained honeycomb-like structure was built up from nanofibers with an average diameter of 370 nm and showed a bimodal distribution of pores: large polygonal pores up to hundreds of micrometers within the honeycomb-cells and irregular pores among the nanofibers ranging around few micrometers. The cell-materials interactions were further studied by culturing MG-63 osteoblast-like cells for 7 days. Cell viability, cell morphology and cell infiltration were comparatively investigated as well. While cells merely proliferated on the surface of non-woven structures, MG-63 cells showed extensive proliferation and deep infiltration up to 100-200 mu m into the honeycomb-like structure. Moreover, the cellular spatial organization was readily regulated by the honeycomb-like pattern as well. Overall, the newly obtained hybrid scaffold may integrate the enhanced osteogenicity originating from the bioactive components, and the improved cell-material interactions brought by the honeycomb-like structure, making the new scaffold a promising candidate for tissue regeneration.

Novel hemp fiber reinforced geopolymer composites were fabricated. The matrix was a new geopolymer based on a mixture of red mud and fly ash. Chopped, randomly oriented hemp fibers were used as reinforcement. The mechanical properties of the geopolymer composite, such as diametral tensile (DTS) (or Brazilian tensile) strength and compressive strength (CS), were measured. The geopolymer composites reinforced with 9 vol.% and 3 vol.% hemp fiber yielded average DTS values of 5.5 MPa and average CS values of 40 MPa. Scanning electron microscopy (SEM) studies were carried out to evaluate the microstructure and fracture surfaces of the composites. The results indicated that the addition of hemp fiber is a promising approach to improve the mechanical strength as well as to modify the failure mechanism of the geopolymer, which changed from brittle to &ldquo, pseudo-ductile&rdquo

The application of a cardiac patch made of biodegradable polymer is a novel approach in regenerative therapies for infarcted cardiac tissue and aims to deliver healthy and functional cells on a mechanically supporting matrix to the damaged area of the myocardium. In this study a novel type of tissue engineered cardiac construct based on poly(glycerol sebacate) (PGS) blended with the corn protein zein was developed. Bead free electrospun PGS–zein fibers were fabricated using acetic acid as a benign solvent. In vitro degradation studies in PBS revealed a physicochemically stable system over a 28 day period showing only a slight drop in pH after 28 days. The results indicate that the novel PGS–zein fibrous structures are attractive biomaterials which can be valuable for cardiac patch applications thus warranting their further investigation in vitro and in vivo.

PHB/PCL/sol-gel derived silica hybrid scaffolds (P5S1S) and PHB/PCL/fumed silica composite scaffolds (P5S1N) with a 5:1 organic/inorganic ratio were fabricated through a combination of electrospinning and sol-gel methods and dispersion electrospinning, respectively. In contrast to the silica nanoparticle aggregates appearing on the fiber surface of P5S1N, smooth and uniform fibers were obtained for P5S1S. The fiber diameter distribution, tensile strength, thermal gravimetric analysis (TGA), and cellular behavior of both types of scaffolds were characterized and studied. The tensile strength results and TGA indicated that the interfacial interaction between the organic and the inorganic phase was enhanced in P5S1S over the nanocomposite scaffolds, and cells exhibited significantly higher alkaline phosphate activity (ALP) for P5S1S, which makes P5S1S hybrid scaffolds candidate materials for bone tissue engineering applications.

The aim of this work is to develop and characterize a multifunctional and dual surface coating system for titanium orthopedic implants by applying two different cost-effective, scalable, and non-complex coating technologies (spray and electrophoretic deposition). The first deposit is formed by a sprayed hybrid sol-gel layer combined with bioactive glass particles (45S5, BG), and the outer part of the dual coating consists of a chitosan-gelatin/silica (Si) - antibiotic (gentamicin, Ge) composite layer applied by electrophoretic deposition. The application of sol-gel enclosed BG drops onto the surface was done to enhance the bioactivity of the double-layered surface coating system. After the BG is dissolved, thus generating a calcium‑silicon rich medium, the re-deposition of hydroxyl‑carbonate apatite occurs. Regarding the antibacterial inhibition properties, antibacterial activity to both strains used (S. aureus and E. coli) was obtained for the chitosan/gelatin/Si[sbnd]Ge nanoparticle coatings on titanium substrates, showing a large inhibition area around the samples. Both the bare Ti samples and the coatings with chitosan/gelatin matrix did not successfully inhibit bacterial growth. As expected, the presence of silica-based glasses and coatings based on amorphous silica enhanced cell viability. The deposition of BG was done with the aim of extending the bioactive effect of the system, considering the presence of a porous degradable organic layer deposited on top, which was shown to be partially degraded after 7 days. The sol gel sprayed BG layer combined with chitosan/gelatin biopolymers filled with Si[sbnd]Ge nanoparticles presents a suitable technology to generate bioactive and antibacterial surfaces to enhance Ti implant performance. Fil: Ballarre, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Aydemir, T.. Friedrich Alexander Universitat; Alemania Fil: Liverani, L.. Institute Of Biomaterials - Friedrich Alexander Univers; Alemania Fil: Roether, Judith A.. Friedrich Alexander Universitat; Alemania Fil: Goldmann, W.H.. Friedrich Alexander Universitat; Alemania Fil: Boccaccini, Aldo R.. Institute Of Biomaterials - Friedrich Alexander Univers; Alemania

Three-dimensional hydrogels are ideal for tissue engineering applications due to their structural integrity and similarity to native soft tissues; however, they can lack mechanical stability. Our objective was to develop a bioactive and mechanically stable hydrogel for clinical application. Auricular cartilage was decellularised using a combination of hypertonic and hypotonic solutions with and without enzymes to produce acellular tissue. Methacryloyl groups were crosslinked with alginate and PVA main chains via 2-aminoethylmathacrylate and the entire macromonomer further crosslinked with the acellular tissue. The resultant hydrogels were characterised for its physicochemical properties (using NMR), in vitro degradation (via GPC analysis), mechanical stability (compression tests) and in vitro biocompatibility (co-culture with bone marrow-derived mesenchymal stem cells). Following decellularisation, the cartilage tissue showed to be acellular at a significant level (DNA content 25.33 ng/mg vs. 351.46 ng/mg control tissue), with good structural and molecular integrity of the retained extra cellular matrix (s-GAG= 0.19 μg/mg vs. 0.65 μg/mg ±0.001 control tissue). Proteomic analysis showed that collagen subtypes and proteoglycans were retained, and SEM and TEM showed preserved matrix ultra-structure. The hybrid hydrogel was successfully cross-linked with biological and polymer components, and it was stable for 30 days in simulated body fluid (poly dispersal index for alginate with tissue was stable at 1.08 and for PVA with tissue was stable at 1.16). It was also mechanically stable (Young’s modulus of 0.46 ± 0.31 KPa) and biocompatible, as it was able to support the development of a multi-cellular feature with active cellular proliferation in vitro. We have shown that it is possible to successfully combine biological tissue with both a synthetic and natural polymer and create a hybrid bioactive hydrogel for clinical application.

Cardiac tissue engineering is a promising strategy to prevent functional deterioration or even to enhance cardiac function upon myocardial infarction. Here, electrospun fiber mats containing different combinations of electrically conductive polyaniline, collagen, and/or hyaluronic acid are assessed regarding material properties and compatibility with cardiomyocyte attachment and function. Microstructure analysis reveals that collagen fiber mats contain a wide range of fiber diameters after crosslinking (from ≈300 nm to ≈5 µm); all other fiber mats contain fibers in the range of ≈120 to ≈300 nm. Fiber mats exhibit comparable electrical conductivity to and greater mechanical properties than the native human myocardium, which is considered beneficial. Cell–matrix interaction analysis utilizing postnatal rat cardiomyocytes reveals that the fiber mats are non‐cytotoxic and permit cell attachment and contraction. Fiber mats containing collagen (9.89%), hyaluronic acid (1.1%), and polyaniline (PANi, 1.34%) exhibit the most favorable properties with longer contraction time, higher contractile amplitude, and lower beating rates. Improved contraction is accompanied by increased connexin 43 expression. Importantly, this fiber mat is a suitable material for human‐induced pluripotent stem cell–derived cardiomyocytes regarding cytotoxicity, cell attachment, and function. Collectively, these data demonstrate that fiber mats made of collagen, hyaluronic acid, and polyaniline are promising materials for cardiac tissue engineering.

Composite 3D scaffolds combining natural polymers and bioceramics are promising candidates for bone tissue engineering (BTE). Zein, as a natural plant protein, offers several advantages, including biocompatibility, adequate strength properties, and low/no immunogenicity; however, it lacks bioactivity. Thus, composite zein: bioactive glass (BG) scaffolds are proposed as promising candidate for BTE applications, with silver-doping of bioactive glass providing an antibacterial effect against possible post-implantation infection. Therefore, the aim of this study was to investigate the in vitro antibacterial properties, biocompatibility, bioactivity and compressive strength of zein scaffolds containing silver-doped bioactive glass. BG nanoparticles, undoped and Ag-doped, were fabricated using the sol-gel method. 3D composite zein:BG scaffolds, containing 20 wt% BG, were prepared and their antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was assessed using the disc diffusion assay. Human osteoblast-like MG-63 cells were used to evaluate the in vitro biocompatibility of the prepared scaffold groups. In addition, the compressive strength of the scaffolds was determined using uniaxial compression strength testing and the scaffold interconnected porosity was measured using helium pycnometer. Disc diffusion assay showed that only zein scaffolds containing Ag-doped sol-gel BG are antibacterially positive against E. coli and S. aureus. Pure zein scaffolds and zein scaffolds containing sol-gel-derived BG showed no negative influence on the growth of MG-63 cells, as evident by the cells' ability to survive, proliferate, and function on these scaffolds. Moreover, incorporating sol-gel-derived BG into zein scaffolds at zein:BG of 80:20 ratio showed bioactive properties with adequate porosity without affecting the scaffolds' compressive strengths, which was similar to that of trabecular bone, suggesting that the new composites have potential for BTE applications in non-loaded bearing areas.

Electrospun hybrid scaffolds are an effective platform to deliver drugs site specifically for the prevention and treatment of diseases in addition to promote tissue regeneration because of the flexibility to load drugs therein. In the present study, electrospun hybrid scaffolds containing antibiotics were developed to support cellular activities and eliminate potential postoperative inflammation and infection. As a model drug, levofloxacin (LFX) was successfully incorporated into pure polyhydroxybutyrate/poly(epsilon-caprolactone) (PHB/PCL) scaffolds and PHB/PCL/sol-gel-derived silica (SGS) scaffolds. The influence of LFX on the morphology, mechanical performance, chemical structure, drug release profile, and antibacterial effect of the scaffolds was thoroughly and comparatively investigated. MG-63 osteoblast-like cell cultivation on both scaffolds certified that LFX inclusion did not impair the biocompatibility. In addition to the favorable cellular proliferation and differentiation, scaffolds containing both LFX and SGS displayed highly increased mineralization content. Therefore, the present multifunctional hybrid scaffolds are promising in tissue engineering applications.

The possibility of extensive incorporation of soda-lime waste glass in the synthesis of fly ash-based geopolymers was investigated. Using waste glass as silica supplier avoids the use of water glass solution as chemical activator. The influence of the addition of waste glass on the microstructure and strength of fly ash-based geopolymers was studied through microstructural and mechanical characterization. Leaching analyses were also carried out. The samples were developed changing the SiO2/Al2O3 molar ratio and the molarity of the sodium hydroxide solution used as alkaline activator. The results suggest that increasing the amount of waste glass as well as increasing the molarity of the solution lead to the formation of zeolite crystalline phases and an improvement of the mechanical strength. Leaching results confirmed that the new geopolymers have the capability to immobilize heavy metal ions.

Given that hormone therapy of osteoporosis with estrogen and progesterone may have potential negative side effects, there is a strong need of developing alternative solutions. Possible therapy alternatives involve the use of phytoestrogens such as daidzein. In this study, daidzein–loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microspheres were prepared using electrospraying. The obtained microspheres had uniform surface morphology, and narrow particle size distribution with mean particle size of 4.8 μm. Daidzein was determined to be in amorphous state in the PHBV microspheres by differential scanning calorimetry analysis. Encapsulated daidzein was released with a low initial burst release (7.6% at 1 h) followed by a sustained release over a period of ~3 days. The developed PHBV microspheres with daidzein delivery function have potential applications in the treatment of osteoporosis and for bone tissue engineering.

A simple yet promising approach to construct bi-layered scaffolds using bioactive ceramics and biodegradable polymers is presented. This method involves two versatile fabrication techniques used in the field of TE: foam replication process and electrospinning. By the foam replication method, three-dimensional 45S5 bioactive glass (BG)-based scaffolds with high porosity, in the range of 95.8 ± 0.9 %, were produced. To improve the mechanical properties of the BG scaffolds, dip-coating using polycaprolactone (PCL) was performed, which led to a significant increase in the compressive strength of the scaffolds. In order to develop a bi-layered construct, bead-less submicrometric fibers of collagen-PCL were electrospun over the PCL-coated BG scaffolds. Surface morphology, surface properties and mechanical strength of the bi-layered construct were evaluated using scanning electron microscopy analysis, contact angle measurements and compressive strength testing, respectively. In vitro degradation of the collagen-PCL fibers in phosphate buffered saline and in vitro bioactivity of the bi-layered constructs in simulated body fluid were investigated. Formation of hydroxyapatite on the PCL-coated BG and along the morphology of the collagen-PCL fibers was ascertained using different characterization techniques. The bi-layered construct is intended for interface tissue engineering applications where the PCL-coated BG scaffold, which is highly bioactive, can serve as a support for the bone side and the composite collagen-PCL submicrometric fibers are intended for the cartilage side.

The present article investigates the use of a novel electrospun fibrous blend of poly(glycerol sebacate) (PGS) and poly(butylene succinate-butylene dilinoleate) (PBS-DLA) as a candidate for cardiac tissue engineering. Random electrospun fibers with various PGS/PBS-DLA compositions (70/30, 60/40, 50/50, and 0/100) were fabricated. To examine the suitability of these fiber blends for heart patches, their morphology, as well as their physical, chemical, and mechanical properties were measured before examining their biocompatibility through cell adhesion. The fabricated fibers were bead-free and exhibited a relatively narrow diameter distribution. The addition of PBS-DLA to PGS resulted in an increase of the average fiber diameter, whereas increasing the amount of PBS-DLA decreased the hydrophilicity and the water uptake of the nanofibrous scaffolds to values that approached those of neat PBS-DLA nanofibers. Moreover, the addition of PBS-DLA significantly increased the elastic modulus. Initial toxicity studies with C2C12 myoblast cells up to 72 h confirmed nontoxic behavior of the blends. Immunofluorescence analyses and scanning electron microscopy analyses confirmed that C2C12 cells showed better cell attachment and proliferation on electrospun mats with higher PBS-DLA content. However, immunofluorescence analyses of the 3-day-old rat cardiomyocytes cultured for 2 and 5 days demonstrated better attachment on the 70/30 fibers containing well-aligned sarcomeres and expressing high amounts of connexin 43 in cellular junctions indicating efficient cell-to-cell communication. It can be concluded, therefore, that fibrous PGS/PBS-DLA scaffolds exhibit promising characteristics as a biomaterial for cardiac patch applications.

Aligned polycaprolactone (PCL) fibers of interest for numerous applications requiring contact guidance and textured topography were fabricated by electrospinning onto a rotating collector using tangential velocities ranging from 0 m/s to 11 m/s. The deposition characteristics of the fibers were investigated by microscopic methods to gather information about fiber diameter, collection angle θ, and number of fibers per reference length. It was shown that the deposition angle ranged from −2.0° to 1.6° and the diameter of the developed fibers averaged 587 nm to 878 nm. Furthermore the deposition angle was found to be independent of the rotation velocity. Homogeneity of the fiber mats was improved with increasing rotation velocity. The number of fibers per reference length, a measure for collection efficiency, proved to be dependent on the rotation velocity, following a modified Weibull function. Hence the collection efficiency of the process can be improved by increasing the rotation velocity above a critical value.

TiO 2 /PLLA nanocomposites were prepared using a two-step process involving electrophoretic deposition (EPD) and dip coating (DC). EPD was carried out first to obtain porous TiO 2 nanostructured coatings while subsequent dip coating was performed using different concentrations of PLLA in dichloromethane (DCM) to obtain nanocomposite materials. According to SEM images, cracks in the TiO 2 nanostructured coatings, developed upon drying, were filled with the polymer which led to improvement of the flexibility of the nanocomposite coatings. Similarly, a surface modification from hydrophilic to hydrophobic was obtained with the addition of the polymer. FTIR analysis showed characteristic bands of both materials, TiO 2 and PLLA, both on the coating surface and at the interphase between the nanocomposite coating and the substrate. Hardness measurements showed a maximum value of 1.4 GPa for TiO 2 –10 wt% PLLA composite. For DMTA tests, detached layers were used and the storage and loss moduli were determined. TiO 2 –PLLA nanocomposite coatings showed higher values of storage modulus at higher temperature in comparison to pure PLLA samples. Also, there was a shift in the glass transition temperature ( T g ) with increasing TiO 2 content. In conclusion, the EPD–DC combined technique proposed here enables the fabrication of nanostructured coatings and free-standing layers in which the quantity of PLLA can be changed according to the intended application, i.e. it is possible to fabricate coatings with tailored degradability and suitable mechanical properties with low additions of PLLA or free standing films with increased flexibility, biodegradability and biocompatibility with high amounts of PLLA.

Surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) has been introduced with lauric acid and oleic acid via co-precipitation and thermal decomposition methods, respectively. This modification is required to increase the stability of SPIONs when incorporated in hydrophobic, biodegradable and biocompatible polymers such as poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). In this work, the solid-in-oil-in-water (S/O/W) emulsion-solvent extraction/evaporation method was utilized to fabricate magnetic polymer microspheres incorporating SPIONs in PHBV. The prepared magnetic PHBV microspheres exhibited particle sizes

Bioactive glass nanoparticles containing copper (Cu-BGNs) were introduced into polycaprolactone (PCL) coating systems to improve the bioactivity, antibacterial properties, and corrosion resistance of vulnerable magnesium matrices under physiological conditions. The influence of different amounts of Cu-BGNs in PCL coatings was thoroughly investigated in determining the wettability, electrochemical properties, and antibacterial effects against Staphylococcus carnosus and Escherichia coli, as well as their cyto-compatibility. Cu-BGNs were observed randomly scattered in PCL coatings. Increasing the concentration of Cu-BGNs resulted in a slight decrease of the water contact angle, and a reduction in anticorrosion properties of the Cu-BGN composite coatings. Yet higher Cu-BGN content in coatings led to more calcium phosphate formation on the surface after 7 days of immersion in Dulbecco's modified Eagle's medium, which was confirmed by Fourier-transform infrared spectroscopy and x-ray photoelectron spectroscopy. The growth of S. carnosus and E. coli was inhibited by Cu2+ ions released from the Cu-BGN coatings. In addition, both direct and indirect cyto-compatibility experiments showed that the viability and proliferation of MG-63 cells on Cu-BGN coatings were highly increased compared to pure magnesium; however, an additional increase of Cu-BGN concentration showed a slight decrease of cell proliferation and cell activity. In summary, Cu-BGN/PCL composite coatings impart magnesium-based biomaterials with antibacterial and anticorrosive properties for clinical applications.

Large bone defects resulting from fractures and disease are a medical concern, being often unable to heal spontaneously by the body’s repair mechanisms. Bone tissue engineering (BTE) is a promising approach for treating bone defects through providing a template to guide osseous regeneration. 3D scaffolds with microstructure mimicking host bone are necessary in common BTE strategies. Bioactive glasses (BGs) attract researchers’ attention as BTE scaffolds as they are osteoconductive and osteoinductive in certain formulations. In vivo animal models allow understanding and evaluation of materials’ performance in the complex physiological environment, being an inevitable step before clinical trials. The aim of this paper is to review for the first time published research investigating the in vivo osseous regenerative capacity of 3D BG scaffolds in bone defect animal models, to better understand and evaluate the progress and future outlook of the use of such scaffolds in BTE. The literature analysis reveals that the regenerative capacity of BG scaffolds depends on several factors; including BG composition, fabrication method, scaffold microstructure and pore characteristics, in addition to scaffold pretreatment and whether or not the scaffolds are loaded with growth factors. In addition, animal species selected, defect size and implantation time affect the scaffold in vivo behavior and outcomes. The review of the literature also makes clear the difficulty encountered to compare different types of bioactive glass scaffolds in their bone forming ability. Even considering such limitations of the current state-of-the-art, results generated from animal bone defect models provide an essential source of information to guide the design of BG scaffolds in future. Statement of Significance Bioactive glasses are at the centre of increasing research efforts in bone tissue engineering as the number of research groups around the world carrying out research on this type of biomaterials continues to increase. However, there are no previous reviews in literature which specifically cover investigations of the performance of bioactive glass scaffolds in bone defect animal models. This is the topic of the present review, in which we have analysed comprehensively all available literature in the field. The review thus fills a gap in the biomaterials literature providing a broad platform of information for researchers interested in bioactive glasses in general and specifically in the outcomes of in vivo models. Bioactive glass scaffolds of different compositions tested in relevant bone defect models are covered.

A novel nanocomposite material which combines the biocompatible, elastomeric, natural, biodegradable homopolymer, poly(3-hydroxyoctanoate), P(3HO), with haemostatic and antibacterial bioactive glass nanoparticles (n-BG), were developed as a matrix for skin related applications. P(3HO) is a unique member of the family of natural polyhydroxyalkanoate biopolymers. The P(3HO)/n-BG composite films were fabricated using the solvent casting method. Microstructural studies revealed n-BG particles both embedded in the matrix and deposited on the surface which introduced nanotopography and increased its hydrophilicity. The composite exhibited an increase in the Young's modulus when compared to the control, yet maintained flexible elastomeric properties. These changes in the surface topography and chemistry of the composite system led to an increase of protein adsorption and cytocompatibility for the seeded human keratinocyte cell line (HaCaT). The results from this study demonstrated that the fabricated P(3HO)/n-BG composite system is a promising novel matrix material with potential applications in skin tissue engineering and wound healing.

Novel composite hydrogels based on the combination of natural polymers; namely alginate and soy protein isolate, and bioactive glass (BG) particles (mean size: 2 μm) were developed. For this purpose a sonochemical approach was used and homogeneous composite hydrogels, incorporating two concentrations of BG particles, were successfully obtained. Further physico-chemical characterization was performed in order to evaluate the influence of each component on hydrogel properties. The water uptake ability, weight loss, protein release, as well as FTIR, SEM and DMTA characterization were carried out. The biomineralization process in simulated body fluid (SBF) was followed over time and the results demonstrated that the composite materials have the ability to form a surface apatite layer after 7 days in SBF. The design of novel composite hydrogels based on soy protein, alginate and BG can be a suitable approach for bone regeneration applications.

PHBV microsphere/45S5 bioactive glass (BG) composite scaffolds with drug release function were developed for bone tissue engineering. BG-based glass-ceramic scaffolds with high porosity (94%) and interconnected pore structure prepared by foam replication method were coated with PHBV microspheres (nominal diameter=3.5 μm) produced by water-in-oil-in-water double emulsion solvent evaporation method. A homogeneous microsphere coating throughout the porous structure of scaffolds was obtained by a simple dip coating method, using the slurry of PHBV microspheres in hexane. Compressive strength tests showed that the microsphere coating slightly improved the mechanical properties of the scaffolds. It was confirmed that the microsphere coating did not inhibit the bioactivity of the scaffolds in SBF. Hydroxyapatite crystals homogeneously grew not only on the struts of the scaffolds but also on the surface of microspheres within 7 days of immersion in SBF. Vancomycin was successfully encapsulated into the PHBV microspheres. The encapsulated vancomycin was released with a dual release profile involving a relatively low initial burst release (21%) and a sustained release (1 month), which is favorable compared to the high initial burst release (77%) and short release period (4 days) measured on uncoated scaffolds. The developed bioactive composite scaffold with drug delivery function has thus the potential to be used advantageously in bone tissue engineering.

Tissue engineering scaffolds are designed to support tissue self-healing within physiological environments by promoting the attachment, growth and differentiation of relevant cells. Newly formed tissue must be supplied with sufficient levels of oxygen to prevent necrosis. Oxygen diffusion is the major transport mechanism before vascularization is completed and oxygen is predominantly supplied via blood vessels. The present study compares different designs for scaffolds in the context of their oxygen diffusion ability. In all cases, oxygen diffusion is confined to the scaffold pores that are assumed to be completely occupied by newly formed tissue. The solid phase of the scaffolds acts as diffusion barrier that locally inhibits oxygen diffusion, i.e. no oxygen passes through the scaffold material. As a result, the oxygen diffusivity is determined by the scaffold porosity and pore architecture. Lattice Monte Carlo simulations are performed to compare the normalized oxygen diffusivities in scaffolds obtained by the foam replication (FR) method, robocasting and sol-gel foaming. Scaffolds made by the FR method were found to have the highest oxygen diffusivity due to their high porosity and interconnected pores. These structures enable the best oxygen supply for newly formed tissue among the scaffold types considered according to the present numerical predictions.