Journal of Functional Biomaterials — Open Access Journal

Multifunctional tissue scaffold material nanodiamond (ND)/chitosan (CS) composites with different diamond concentrations from 1 wt % to 5 wt % were synthesized through a solution casting method. The microstructure and mechanical properties of the composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and nanoindentation. Compared with pristine CS, the addition of ND resulted in a significant improvement of mechanical properties, including a 239%, 276%, 321%, 333%, and 343% increase in Young’s modulus and a 68%, 96%, 114%, 118%, and 127% increase in hardness when the ND amount was 1 wt %, 2 wt %, 3 wt %, 4 wt %, and 5 wt %, respectively. The strong interaction between ND surface groups and the chitosan matrix plays an important role in improving mechanical properties. Full article

Hydrogels are an attractive class of tunable material platforms that, combined with their structural and functional likeness to biological environments, have a diversity of applications in bioengineering. Several polymers, natural and synthetic, can be used, the material selection being based on the required functional characteristics of the prepared hydrogels. Silk fibroin (SF) is an attractive natural polymer for its excellent processability, biocompatibility, controlled degradation, mechanical properties and tunable formats and a good candidate for the fabrication of hydrogels. Tremendous effort has been made to control the structural and functional characteristic of silk hydrogels, integrating novel biological features with advanced processing techniques, to develop the next generation of functional SF hydrogels. Here, we review the several processing methods developed to prepare advanced SF hydrogel formats, emphasizing a bottom-up approach beginning with critical structural characteristics of silk proteins and their behavior under specific gelation environments. Additionally, the preparation of SF hydrogel blends and other advanced formats will also be discussed. We conclude with a brief description of the attractive utility of SF hydrogels in relevant bioengineering applications. Full article

In this study, we report a novel three-component luminescent hydrogel, which is composed of amino acid derivatives (N,N′-di valine-3,4,9,10-perylenetetracarboxylic acid, NVPD), riboflavin (RF), and melamine (MM). The three-component hydrogel is attributed to multiple hydrogen bonds and the strong π-π stacking interaction between these molecules. Based on the strong hydrogen bonding of the gelator, when the reversible process between the gel and the solution take places it changes the pH of the system from 6.1 to 10.6. In addition, green fluorescence could be the emissive of the hydrogel under 498 nm and the conversion process of the aggregation state repeated reversibly by altering the value of ambient pH. This pH-responsive luminescent gel may display potential for use in nano pH sensors. Full article

A photocrosslinkable trehalose derivative carrying mesogenic groups was synthesized by esterification reactions. The derivative (TC-HBPHA) was synthesized by the reaction of partially cinnamoyl-modified trehalose (TC4) with 4-(4-hexyloxybenzoyloxy)phenoxy-6-oxohexanoic acid (HBPHA) as a mesogenic unit. TC-HBPHA showed a nematic liquid crystalline mesophase at a temperature range from 150 °C to 175 °C in the heating process under observation with a polarized optical microscope. The dimerization of the cinnamoyl groups of TC-HBPHA by ultraviolet (UV) light irradiation was monitored by ultraviolet-visible (UV-Vis) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. The photocrosslinked film was obtained after the UV irradiation of TC-HBPHA, and it kept the liquid crystalline mesophase at almost the same temperature range. Fibroblast cells cultured on the photocrosslinked TC-HBPHA proliferated as well as on the polystyrene culture plate, indicating that the film has no toxicity. Interestingly, some cells on photocrosslinked TC-HBPHA had a spindle shape and aligned characteristically. Full article

Although a lot of in vitro and in vivo assays have been performed during the last few decades years for hydroxyapatite bioactive coatings, there is a lack of exploitation of real-time in vitro interaction measurements. In the present work, real-time interactions for a plasma sprayed hydroxyapatite coating were measured by a Multi-Parametric Surface Plasmon Resonance (MP-SPR), and the results were compared with standard traditional cell viability in vitro assays. MP-SPR is proven to be suitable not only for measurement of molecule–molecule interactions but also molecule–material interaction measurements and cell interaction. Although SPR is extensively utilized in interaction studies, recent research of protein or cell adsorption on hydroxyapatite coatings for prostheses applications was not found. The as-sprayed hydroxyapatite coating resulted in 62.4% of crystalline phase and an average thickness of 24 ± 6 μm. The MP-SPR was used to measure lysozyme protein and human mesenchymal stem cells interaction to the hydroxyapatite coating. A comparison between the standard gold sensor and Hydroxyapatite (HA)-plasma coated sensor denoted a clearly favourable cell attachment on HA coated sensor as a significantly higher signal of cell binding was detected. Moreover, traditional cell viability and proliferation tests showed increased activity with culture time indicating that cells were proliferating on HA coating. Cells show homogeneous distribution and proliferation along the HA surface between one and seven days with no significant mortality. Cells were flattened and spread on rough surfaces from the first day, with increasing cytoplasmatic extensions during the culture time. Full article

Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world’s best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration. Full article

Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390–420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications. Full article

An emerging concept is that cancers strongly depend on both internal and external signals for growth and invasion. In this review, we will discuss pathological and physical changes in the tumor microenvironment and how these changes can be exploited to design gold nanoparticles for cancer diagnosis and therapy. These intrinsic changes include extracellular and intracellular pH, extracellular matrix enzymes, and glutathione concentration. External stimuli include the application of laser, ultrasound and X-ray. The biology behind these changes and the chemistry behind the responding mechanisms to these changes are reviewed. Examples of recent in vitro and in vivo studies are also presented, and the clinical implications of these findings are discussed. Full article

Mechanical properties of a scaffold play an important role in its in vivo performance in bone tissue engineering, due to the fact that implanted scaffolds are typically subjected to stress including compression, tension, torsion, and shearing. Unfortunately, not all the materials used to fabricate scaffolds are strong enough to mimic native bones. Extensive research has been conducted in order to increase scaffold strength and mechanical performance by incorporating nanoparticles and/or coatings. An incredible improvement has been achieved; and some outstanding examples are the usage of nanodiamond, hydroxyapatite, bioactive glass particles, SiO₂, MgO, and silver nanoparticles. This review paper aims to present the results, to summarize significant findings, and to give perspective for future work, which could be beneficial to future bone tissue engineering. Full article

The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the literature of surface erosion with the experimentally-identified model parameters. Acceptable agreement between experimental results and model predictions was observed for scaffolds in a cylindrical shape, made from poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL). This study illustrates that geometry evaluation by synchrotron-based imaging is an effective means to in situ characterize the scaffold mass loss as well as possibly other degradation-related properties. Full article

This article is an updated review of the published literature on glass-ionomer cements and covers their structure, properties and clinical uses within dentistry, with an emphasis on findings from the last five years or so. Glass-ionomers are shown to set by an acid-base reaction within 2–3 min and to form hard, reasonably strong materials with acceptable appearance. They release fluoride and are bioactive, so that they gradually develop a strong, durable interfacial ion-exchange layer at the interface with the tooth, which is responsible for their adhesion. Modified forms of glass-ionomers, namely resin-modified glass-ionomers and glass carbomer, are also described and their properties and applications covered. Physical properties of the resin-modified glass-ionomers are shown to be good, and comparable with those of conventional glass-ionomers, but biocompatibility is somewhat compromised by the presence of the resin component, 2 hydroxyethyl methacrylate. Properties of glass carbomer appear to be slightly inferior to those of the best modern conventional glass-ionomers, and there is not yet sufficient information to determine how their bioactivity compares, although they have been formulated to enhance this particular feature. Full article

Disorders affecting the temporomandibular joint (TMJ) are a long-standing health concern. TMJ disorders (TMJD) are often associated with an internal disc derangement accompanied by a suite of symptoms including joint noises, jaw dysfunction, and severe pain. The severity of patient symptoms and their reoccurrence can be alleviated to some extent with conservative therapy; however, refractory cases often require surgery that has shown only limited success. Bioengineered scaffolds with cell supportive surfaces an d nanoarchitectures that mimic TMJ tissue structure may offer an alternative treatment modality. In this study, titanium dioxide (TiO₂) nanothin films, fabricated by layer-by-layer assembly, were examined as means for creating such a scaffold. The viability and growth of TMJ discal fibrochondrocytes (FCs) were assessed through MTT and DNA assays and total protein content over a 14-day experimental period. ELISA was also used to measure expression of types I and II collagen, decorin and aggrecan. Quantitative analyses demonstrated that FCs synthesized characteristic discal matrix proteins, with an increased production of type I collagen and decorin as opposed to collagen type II and aggrecan. A stimulatory effect on discal FC proliferation and extracellular matrix (ECM) expression with thicker nanofilms was also observed. The cumulative results suggest that TiO₂ nanofilms may have potential as a TMJ scaffolding material. Full article

A layered construct was developed by combining a porous polymer sheet and a cell sheet as a tissue engineered vascular patch. The primary objective of this study is to investigate the influence of mesenchymal stem cells (MSCs) sheet on the tensile mechanical properties of porous poly-(l-lactide-co-ε-caprolactone) (PLCL) sheet. The porous PLCL sheet was fabricated by the solid-liquid phase separation method and the following freeze-drying method. The MSCs sheet, prepared by the temperature-responsive dish, was then layered on the top of the PLCL sheet and cultured for 2 weeks. During the in vitro study, cellular properties such as cell infiltration, spreading and proliferation were evaluated. Tensile test of the layered construct was performed periodically to characterize the tensile mechanical behavior. The tensile properties were then correlated with the cellular properties to understand the effect of MSCs sheet on the variation of the mechanical behavior during the in vitro study. It was found that MSCs from the cell sheet were able to migrate into the PLCL sheet and actively proliferated into the porous structure then formed a new layer of MSCs on the opposite surface of the PLCL sheet. Mechanical evaluation revealed that the PLCL sheet with MSCs showed enhancement of tensile strength and strain energy density at the first week of culture which is characterized as the effect of MSCs proliferation and its infiltration into the porous structure of the PLCL sheet. New technique was presented to develop tissue engineered patch by combining MSCs sheet and porous PLCL sheet, and it is expected that the layered patch may prolong biomechanical stability when implanted in vivo. Full article

Since its discovery in the years of the French Revolution, the field of keratoprostheses has evolved significantly. However, the path towards its present state has not always been an easy one. Initially discarded for its devastating complications, the introduction of new materials and the discovery of antibiotics in the last century gave new life to the field. Since then, the use of keratoprostheses for severe ocular surface disorders and corneal opacities has increased significantly, to the point that it has become a standard procedure for corneal specialists worldwide. Although the rate of complications has significantly been reduced, these can impede the long-term success, since some of them can be visually devastating. In an attempt to overcome these complications, researchers in the field have been recently working on improving the design of the currently available devices, by introducing the use of new materials that are more biocompatible with the eye. Here we present an update on the most recent research in the field. Full article

Blood vessel reconstruction is still an elusive goal for the development of in vitro models as well as artificial vascular grafts. In this study, we used a novel photo-curable cytocompatible polyacrylate material (PA) for freeform generation of synthetic vessels. We applied stereolithography for the fabrication of arbitrary 3D tubular structures with total dimensions in the centimeter range, 300 µm wall thickness, inner diameters of 1 to 2 mm and defined pores with a constant diameter of approximately 100 µm or 200 µm. We established a rinsing protocol to remove remaining cytotoxic substances from the photo-cured PA and applied thio-modified heparin and RGDC-peptides to functionalize the PA surface for enhanced endothelial cell adhesion. A rotating seeding procedure was introduced to ensure homogenous endothelial monolayer formation at the inner luminal tube wall. We showed that endothelial cells stayed viable and adherent and aligned along the medium flow under fluid-flow conditions comparable to native capillaries. The combined technology approach comprising of freeform additive manufacturing (AM), biomimetic design, cytocompatible materials which are applicable to AM, and biofunctionalization of AM constructs has been introduced as BioRap^® technology by the authors. Full article

Calcium phosphate bone cements (CPCs) with antibacterial properties are demanded for clinical applications. In this study, we demonstrated the use of a relatively simple processing route based on preparation of silver-doped CPCs (CPCs-Ag) through the preparation of solid dispersed active powder phase. Real-time monitoring of structural transformations and kinetics of several CPCs-Ag formulations (Ag = 0 wt %, 0.6 wt % and 1.0 wt %) was performed by the Energy Dispersive X-ray Diffraction technique. The partial conversion of β-tricalcium phosphate (TCP) phase into the dicalcium phosphate dihydrate (DCPD) took place in all the investigated cement systems. In the pristine cement powders, Ag in its metallic form was found, whereas for CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, CaAg(PO₃)₃ was detected and Ag (met.) was no longer present. The CPC-Ag 0 wt % cement exhibited a compressive strength of 6.5 ± 1.0 MPa, whereas for the doped cements (CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt %) the reduced values of the compressive strength 4.0 ± 1.0 and 1.5 ± 1.0 MPa, respectively, were detected. Silver-ion release from CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, measured by the Atomic Emission Spectroscopy, corresponds to the average values of 25 µg/L and 43 µg/L, respectively, rising a plateau after 15 days. The results of the antibacterial test proved the inhibitory effect towards pathogenic Escherichia coli for both CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, better performances being observed for the cement with a higher Ag-content. Full article

The articulating surfaces of four different sizes of unused pyrolytic carbon proximal interphalangeal prostheses (PIP) were evaluated though measuring several topographical parameters using a white light interferometer: average roughness (S_a); root mean-square roughness (S_q); skewness (S_sk); and kurtosis (S_ku). The radii of the articulating surfaces were measured using a coordinate measuring machine, and were found to be: 2.5, 3.3, 4.2 and 4.7 mm for proximal, and 4.0, 5.1, 5.6 and 6.3 mm for medial components. ANOVA was used to assess the relationship between the component radii and each roughness parameter. S_a, S_q and S_sk correlated negatively with radius (p = 0.001, 0.001, 0.023), whilst S_ku correlated positively with radius (p = 0.03). Ergo, the surfaces with the largest radii possessed the better topographical characteristics: low roughness, negative skewness, high kurtosis. Conversely, the surfaces with the smallest radii had poorer topographical characteristics. Full article

Glass polyalkenoate cements (GPCs) have potential for skeletal cementation. Unfortunately, commercial GPCs all contain, and subsequently release, aluminum ions, which have been implicated in degenerative brain disease. The purpose of this research was to create a series of aluminum-free GPCs constructed from silicate (SiO₂), calcium (CaO), zinc (ZnO) and sodium (Na₂O)-containing glasses mixed with poly-acrylic acid (PAA) and to evaluate the potential of these cements for cranioplasty applications. Three glasses were formulated based on the SiO₂-CaO-ZnO-Na₂O parent glass (KBT01) with 0.03 mol % (KBT02) and 0.06 mol % (KBT03) germanium (GeO₂) substituted for ZnO. Each glass was then mixed with 50 wt % of a patented SiO₂-CaO-ZnO-strontium (SrO) glass composition and the resultant mixtures were subsequently reacted with aqueous PAA (50 wt % addition) to produce three GPCs. The incorporation of Ge in the glass phase was found to result in decreased working (142 s to 112 s) and setting (807 s to 448 s) times for the cements manufactured from them, likely due to the increase in crosslink formation between the Ge-containing glasses and the PAA. Compressive (σ_c) and biaxial flexural (σ_f) strengths of the cements were examined at 1, 7 and 30 days post mixing and were found to increase with both maturation and Ge content. The bonding strength of a titanium cylinder (Ti) attached to bone by the cements increased from 0.2 MPa, when placed, to 0.6 MPa, after 14 days maturation. The results of this research indicate that Germano-Silicate based GPCs have suitable handling and mechanical properties for cranioplasty fixation. Full article