Enhanced Electroactive Phases of Poly(vinylidene Fluoride) Fibers for Tissue Engineering Applications.

Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering with piezoelectricity similar to bone. One of the prospective candidates is highly piezoelectric poly(vinylidene fluoride) (PVDF), which was used for fibrous scaffold formation by electrospinning. In this study, we focused on the effect of PVDF molecular weight (180,000 g/mol and 530,000 g/mol) and process parameters, such as the rotational speed of the collector, applied voltage, and solution flow rate on the properties of the final scaffold. Fourier Transform Infrared Spectroscopy allows for determining the effect of molecular weight and processing parameters on the content of the electroactive phases. It can be concluded that the higher molecular weight of the PVDF and higher collector rotational speed increase nanofibers' diameter, electroactive phase content, and piezoelectric coefficient. Various electrospinning parameters showed changes in electroactive phase content with the maximum at the applied voltage of 22 kV and flow rate of 0.8 mL/h. Moreover, the cytocompatibility of the scaffolds was confirmed in the culture of human adipose-derived stromal cells with known potential for osteogenic differentiation. Based on the results obtained, it can be concluded that PVDF scaffolds may be taken into account as a tool in bone tissue engineering and are worth further investigation.

Development of Poly(methyl methacrylate)/nano-hydroxyapatite (PMMA/nHA) Nanofibers for Tissue Engineering Regeneration Using an Electrospinning Technique.

The study explores the in vitro biocompatibility and osteoconductivity of poly(methyl methacrylate)/nano-hydroxyapatite (PMMA/nHA) composite nanofibrous scaffolds for bone tissue engineering (BTE). Electrospun scaffolds, exhibiting both low and high fiber orientation, were investigated. The inclusion of hydroxyapatite nanoparticles enhances the osteoconductivity of the scaffolds while maintaining the ease of fabrication through electrospinning. SEM analysis confirms the high-quality morphology of the scaffolds, with successful incorporation of nHA evidenced by SEM-EDS and FTIR methods. DSC analysis indicates that nHA addition increases the PMMA glass transition temperature (Tg) and reduces stress relaxation during electrospinning. Furthermore, higher fiber orientation affects PMMA Tg and stress relaxation differently. Biological studies demonstrate the composite material's non-toxicity, excellent osteoblast viability, attachment, spreading, and proliferation. Overall, PMMA/nHA composite scaffolds show promise for BTE applications.

Electrospun Poly(vinyl alcohol)-Based Conductive Semi-interpenetrating Polymer Network Fibrous Hydrogel: A Toolbox for Optimal Cross-Linking.

Cross-linking of poly(vinyl alcohol) (PVA) creates a three-dimensional network by bonding adjacent polymer chains. The cross-linked structure, upon immersion in water, turns into a hydrogel, which exhibits unique absorption properties due to the presence of hydrophilic groups within the PVA polymer chains and, simultaneously, ceases to be soluble in water. The properties of PVA can be adjusted by chemical modification or blending with other substances, such as polymers, e.g., conductive poly[3-(potassium-5-butanoate)thiophene-2,5-diyl] (P3KBT). In this work, PVA-based conductive semi-interpenetrating polymer networks (semi-IPNs) are successfully fabricated. The systems are obtained as a result of electrospinning of PVA/P3KBT precursor solutions with different polymer concentrations and then cross-linking using "green", environmentally safe methods. One approach consists of thermal treatment (H), while the second approach combines stabilization with ethanol and heating (E). The comprehensive characterization allows to evaluate the correlation between the cross-linking methods and properties of nanofibrous hydrogels. While both methods are successful, the cross-linking density is higher in the thermally cross-linked samples, resulting in lower conductivity and swelling ratio compared to the E-treated samples. Moreover, the H-cross-linked systems have better mechanical properties-lower stiffness and greater tensile strength. All the tested systems are biocompatible, and interestingly, due to the presence of P3KBT, they show photoresponsivity to solar radiation generated by the simulator. The results indicate that both methods of PVA cross-linking are highly effective and can be applied to a specific system depending on the target, e.g., biomedical or electronic applications.

A facile one-stone-two-birds strategy for fabricating multifunctional 3D nanofibrous scaffolds.

Local bacterial infections lead to delayed wound healing and in extreme cases, such as diabetic foot ulcers, to non-healing due to the impaired cellular function in such wounds. Thus, many scientists have focused on developing advanced therapeutic platforms to treat infections and promote cellular proliferation and angiogenesis. This study presents a facile approach for designing nanofibrous scaffolds in three dimensions (3D) with enhanced antibacterial activity to meet the need of treating chronic diabetic wounds. Being a cationic surfactant as well as an antimicrobial agent, octenidine (OCT) makes a 2D membrane hydrophilic, enabling it to be modified into a 3D scaffold in a "one stone, two birds" manner. Aqueous sodium borohydride (NaBH4) solution plays a dual role in the fabrication process, functioning as both a reducing agent for the in situ synthesis of silver nanoparticles (Ag NPs) anchored on the nanofiber surface and a hydrogen gas producer for expanding the 2D membranes into fully formed 3D nanofiber scaffolds, as demonstrated by morphological analyses. Various techniques were used to characterize the developed scaffold (e.g., SEM, XRD, DSC, FTIR, and surface wettability), demonstrating a multilayered porous structure and superhydrophilic properties besides showing sustained and prolonged release of OCT (61% ± 1.97 in 144 h). Thanks to the synergistic effect of OCT and Ag NPs, the antibacterial performance of the 3D scaffold was significantly higher than that of the 2D membrane. Moreover, cell viability was studied in vitro on mouse fibroblasts L929, and the noncytotoxic character of the 3D scaffold was confirmed. Overall, it is shown that the obtained multifunctional 3D scaffold is an excellent candidate for diabetic wound healing and skin repair.

A methylcellulose/agarose hydrogel as an innovative scaffold for tissue engineering.

In situ crosslinked materials are the main interests of both scientific and industrial research. Methylcellulose (MC) aqueous solution is one of the representatives that belongs to this family of thermosensitive materials. At room temperature, MC is a liquid whereupon during temperature increase up to 37 °C, it crosslinks physically and turns into a hydrogel. This feature makes it unique, especially for tissue engineering applications. However, the crosslinking rate of MC alone is relatively slow considering tissue engineering expectations. According to these expectations, the crosslinking should take place slowly enough to allow for complete injection and fill the injury avoiding clogging in the needle, and simultanously, it should be sufficiently fast to prevent it from relocation from the lesion. One of the methods to overcome this problem is MC blending with another substance that increases the crosslinking rate of MC. In these studies, we used agarose (AGR). These studies aim to investigate the effect of different AGR amounts on MC crosslinking kinetics, and thermal, viscoelastic, and biological properties. Differential Scanning Calorimetry (DSC) and dynamic mechanical analysis (DMA) measurements proved that AGR addition accelerates the beginning of MC crosslinking. This phenomenon resulted from AGR's greater affinity to water, which is crucial in this particular crosslinking part. In vitro tests, carried out using the L929 fibroblast line and mesenchymal stem cells (MSCs), confirmed that most of the hydrogel samples were non-cytotoxic in contact with extracts and directly with cells. Not only does this type of thermosensitive hydrogel system provide excellent mechanical and biological cues but also its stimuli-responsive character provides more novel functionalities for designing innovative scaffold/cell delivery systems for tissue engineering applications.

Toward a Better Understanding of the Gelation Mechanism of Methylcellulose via Systematic DSC Studies.

A methylcellulose (MC) is one of the materials representatives performing unique thermal-responsive properties. While reaching a critical temperature upon heating MC undergoes a physical sol-gel transition and consequently becomes a gel. The MC has been studied for many years and researchers agree that the MC gelation is related to the lower critical solution temperature (LCST). Nevertheless, a precise description of the MC gelation mechanism remains under discussion. In this study, we explained the MC gelation mechanism through examination of a wide range of MC concentrations via differential scanning calorimetry (DSC). The results evidenced that MC gelation is a multistep thermoreversible process, manifested by three and two endotherms depending on MC concentration. The occurrence of the three endotherms for low MC concentrations during heating has not been reported in the literature before. We justify this phenomenon by manifestation of three various transitions. The first one manifests water-water interactions, i.e., spanning water network breakdown into small water clusters. It is clearly evidenced by additional normalization to the water content. The second effect corresponds to polymer-water interactions, i.e., breakdown of water cages surrounded methoxy groups of MC. The last one is related to the polymer-polymer interactions, i.e., fibril hydrophobic domain formation. Not only did these results clarify the MC crosslinking mechanism, but also in the future will help to assess MC relevance for various potential application fields.

Advances in 3D Printing for Tissue Engineering.

Tissue engineering (TE) scaffolds have enormous significance for the possibility of regeneration of complex tissue structures or even whole organs. Three-dimensional (3D) printing techniques allow fabricating TE scaffolds, having an extremely complex structure, in a repeatable and precise manner. Moreover, they enable the easy application of computer-assisted methods to TE scaffold design. The latest additive manufacturing techniques open up opportunities not otherwise available. This study aimed to summarize the state-of-art field of 3D printing techniques in applications for tissue engineering with a focus on the latest advancements. The following topics are discussed: systematics of the available 3D printing techniques applied for TE scaffold fabrication; overview of 3D printable biomaterials and advancements in 3D-printing-assisted tissue engineering.

Progress in the Applications of Smart Piezoelectric Materials for Medical Devices.

Smart piezoelectric materials are of great interest due to their unique properties. Piezoelectric materials can transform mechanical energy into electricity and vice versa. There are mono and polycrystals (piezoceramics), polymers, and composites in the group of piezoelectric materials. Recent years show progress in the applications of piezoelectric materials in biomedical devices due to their biocompatibility and biodegradability. Medical devices such as actuators and sensors, energy harvesting devices, and active scaffolds for neural tissue engineering are continually explored. Sensors and actuators from piezoelectric materials can convert flow rate, pressure, etc., to generate energy or consume it. This paper consists of using smart materials to design medical devices and provide a greater understanding of the piezoelectric effect in the medical industry presently. A greater understanding of piezoelectricity is necessary regarding the future development and industry challenges.

Hydrophilic Surface Functionalization of Electrospun Nanofibrous Scaffolds in Tissue Engineering.

Electrospun polymer nanofibers have received much attention in tissue engineering due to their valuable properties such as biocompatibility, biodegradation ability, appropriate mechanical properties, and, most importantly, fibrous structure, which resembles the morphology of extracellular matrix (ECM) proteins. However, they are usually hydrophobic and suffer from a lack of bioactive molecules, which provide good cell adhesion to the scaffold surface. Post-electrospinning surface functionalization allows overcoming these limitations through polar groups covalent incorporation to the fibers surface, with subsequent functionalization with biologically active molecules or direct deposition of the biomolecule solution. Hydrophilic surface functionalization methods are classified into chemical approaches, including wet chemical functionalization and covalent grafting, a physiochemical approach with the use of a plasma treatment, and a physical approach that might be divided into physical adsorption and layer-by-layer assembly. This review discusses the state-of-the-art of hydrophilic surface functionalization strategies of electrospun nanofibers for tissue engineering applications. We highlighted the major advantages and drawbacks of each method, at the same time, pointing out future perspectives and solutions in the hydrophilic functionalization strategies.

The Role of Electrical Polarity in Electrospinning and on the Mechanical and Structural Properties of As-Spun Fibers.

Electric field strength and polarity in electrospinning processes and their effect on process dynamics and the physical properties of as-spun fibers is studied. Using a solution of the neutral polymer such as poly(methyl methacrylate) (PMMA) we explored the electrospun jet motion issued from a Taylor cone. We focused on the straight jet section up to the incipient stage of the bending instability and on the radius of the disk of the fibers deposited on the collecting electrode. A new correlation formula using dimensionless parameters was found, characterizing the effect of the electric field on the length of the straight jet, L˜E~E˜0.55. This correlation was found to be valid when the spinneret was either negatively or positively charged and the electrode grounded. The fiber deposition radius was found to be independent of the electric field strength and polarity. When the spinneret was negatively charged, L˜E was longer, the as-spun fibers were wider. The positively charged setup resulted in fibers with enhanced mechanical properties and higher crystallinity. This work demonstrates that often-overlooked electrical polarity and field strength parameters influence the dynamics of fiber electrospinning, which is crucial for designing polymer fiber properties and optimizing their collection.

Enhanced Piezoelectricity of Electrospun Polyvinylidene Fluoride Fibers for Energy Harvesting.

Piezoelectric polymers are promising energy materials for wearable and implantable applications for replacing bulky batteries in small and flexible electronics. Therefore, many research studies are focused on understanding the behavior of polymers at a molecular level and designing new polymer-based generators using polyvinylidene fluoride (PVDF). In this work, we investigated the influence of voltage polarity and ambient relative humidity in electrospinning of PVDF for energy-harvesting applications. A multitechnique approach combining microscopy and spectroscopy was used to study the content of the ß-phase and piezoelectric properties of PVDF fibers. We shed new light on ß-phase crystallization in electrospun PVDF and showed the enhanced piezoelectric response of the PVDF fiber-based generator produced with the negative voltage polarity at a relative humidity of 60%. Above all, we proved that not only crystallinity but also surface chemistry is crucial for improving piezoelectric performance in PVDF fibers. Controlling relative humidity and voltage polarity increased the d33 piezoelectric coefficient for PVDF fibers by more than three times and allowed us to generate a power density of 0.6 µW·cm-2 from PVDF membranes. This study showed that the electrospinning technique can be used as a single-step process for obtaining a vast spectrum of PVDF fibers exhibiting different physicochemical properties with ß-phase crystallinity reaching up to 74%. The humidity and voltage polarity are critical factors in respect of chemistry of the material on piezoelectricity of PVDF fibers, which establishes a novel route to engineer materials for energy-harvesting and sensing applications.

Piezoelectric Scaffolds as Smart Materials for Neural Tissue Engineering.

Injury to the central or peripheral nervous systems leads to the loss of cognitive and/or sensorimotor capabilities, which still lacks an effective treatment. Tissue engineering in the post-injury brain represents a promising option for cellular replacement and rescue, providing a cell scaffold for either transplanted or resident cells. Tissue engineering relies on scaffolds for supporting cell differentiation and growth with recent emphasis on stimuli responsive scaffolds, sometimes called smart scaffolds. One of the representatives of this material group is piezoelectric scaffolds, being able to generate electrical charges under mechanical stimulation, which creates a real prospect for using such scaffolds in non-invasive therapy of neural tissue. This paper summarizes the recent knowledge on piezoelectric materials used for tissue engineering, especially neural tissue engineering. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges, and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and serves as a starting point for novel research pathways in the most relevant and challenging open questions.

Crosslinking Kinetics of Methylcellulose Aqueous Solution and Its Potential as a Scaffold for Tissue Engineering.

Thermosensitive, physically crosslinked injectable hydrogels are in the area of interests of various scientific fields. One of the representatives of this materials group is an aqueous solution of methylcellulose. At ambient conditions, methylcellulose (MC) is a sol while on heating up to 37 °C, MC undergoes physical crosslinking and transforms into a gel. Injectability at room temperature, and crosslinkability during subsequent heating to physiological temperature raises hopes, especially for tissue engineering applications. This research work aimed at studying crosslinking kinetics, thermal, viscoelastic, and biological properties of MC aqueous solution in a broad range of MC concentrations. It was evidenced by Differential Scanning Calorimetry (DSC) that crosslinking of MC is a reversible two-stage process, manifested by the appearance of two endothermic effects, related to the destruction of water cages around methoxy groups, followed by crosslinking via the formation of hydrophobic interactions between methoxy groups in the polymeric chains. The DSC results also allowed the determination of MC crosslinking kinetics. Complementary measurements of MC crosslinking kinetics performed by dynamic mechanical analysis (DMA) provided information on the final storage modulus, which was important from the perspective of tissue engineering applications. Cytotoxicity tests were performed using mouse fibroblasts and showed that MC at low concentration did not cause cytotoxicity. All these efforts allowed to assess MC hydrogel relevance for tissue engineering applications.

Electrospinning polyelectrolyte complexes: pH-responsive fibers.

Fibers were electrospun from a solution comprised of oppositely charged polyelectrolytes, in efforts to achieve highly confined macromolecular packaging. A stoichiometric ratio of poly(allylamine hydrochloride) and poly(acrylic acid) solution was mixed in an ethanol-water co-solvent. Differential scanning calorimetry (DSC) analysis of electrospun fibers demonstrated no indication of glass transition, Tg. Infrared spectroscopy (FTIR) analysis of the fibers as a function of temperature, demonstrated an amidation process at lower temperature compared to cast film. Polarized FTIR indicated a preference of the functional groups to be perpendicular to the fiber axis. These results imply formation of mixed phase fibers with enhanced conditions for intermolecular interactions, due to the highly aligned and confined assembly of the macromolecules. The tunable intermolecular interactions between the functional groups of the polyelectrolytes, impact pH-driven, reversible swelling-deswelling of the fibers. The degree of ionization of PAA at pH 5.5 and pH 1.8 varied from 85% to 18%, correspondingly, causing transformation of ionic interactions to hydrogen bonding between the functional groups. The chemical change led to a massive water diffusion of 500% by weight and to a marked increase of 400% in fiber diameter, at a rate of 0.50 µm s(-1). These results allow for manipulation and tailoring of key fiber properties for tissue engineering, membranes, and artificial muscle applications.