Sterilization of devices is important in hospitals, operating theatres, and emergency rooms. Microdialysis allows in vivo sampling of small molecules and is used for clinical studies. Microdialysis probes are made of soft, flexible, porous polymeric membranes. They have been traditionally disinfected using either ethanol (which fails to eliminate all microbes and doesn't satisfy regulatory requirements) or ethylene oxide gas and gamma irradiation (that are expensive and resource-intensive). In this work, three methods for microdialysis probe-sterilization were studied - autoclave and two chemicals (commercially available sterilization solutions): Sporox II and MetriCide. Following sterilization, the regenerated cellulose membranes were characterized under scanning electron microscopy and by measuring the changes in pore characteristics using nitrogen sorption. To determine the effect of sterilization on analyte diffusion through the membrane, microdialysis probes were fabricated, sterilized and tested with two analytes; ethanol and dopamine. The autoclaved membranes suffered thermo-mechanical damage and were deemed unfit for further testing. Probes sterilized with the chemical solutions were subsequently characterized by in vitro microdialysis experiments performed under regulated mass flux conditions. It is concluded that autoclaving is not a suitable sterilization technique for the cellulose membranes, while both of the chemical sterilizers were found to be good candidates for sterilization.

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pK, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference-based applications.

Tissue engineering provides promise for regeneration of cardiac tissue following myocardial infarction. However, the harsh microenvironment of the infarct hampers the efficacy of regenerative therapies. Ischemia-reperfusion injury dramatically increases the levels of reactive oxygen species (ROS) within the infarcted area, causing a cascade of further cellular injury. Implantable tissue engineered grafts can target this oxidative stress by delivering pharmaceutical compounds directly into the diseased tissue. Herein, we successfully fabricated electrospun polycaprolactone (PCL) fibers containing varying concentrations of ascorbic acid, a potent antioxidant well known for its ROS-scavenging capabilities. The antioxidant scaffolds displayed significantly improved scavenging of DPPH radicals, superoxide anions and hydroxyl radicals, in a dose dependent manner. Mechanical properties testing indicated that incorporation of ascorbic acid enhanced the strength and Young's modulus of the material, correlating with a moderate but non-significant increase in the crystallinity. Moreover, the scaffolds supported adhesion and maintained survival of human umbilical vein endothelial cells in vitro, indicating good cytocompatibility. These results provide motivation for the use of ascorbic acid-containing fibrous scaffolds to regulate the highly oxidative microenvironment following myocardial infarction.

Extrusion printing represents one of the leading additive manufacturing techniques for tissue engineering purposes due to the possibility of achieving accurate control of the final shape and porosity of the scaffold. Despite many polymeric materials having already been optimized for this application, the processing of biopolymer-based systems still presents several limitations mainly ascribed to their poor rheological properties. Moreover, the introduction of inorganic components into the biomaterial formulation may introduce further difficulties related to system homogeneity, finally compromising its extrudability. In this context, the present study aimed at developing a new multi-phase biomaterial ink able to mimic the native composition of bone extracellular matrix, combining type-I-collagen with nano-hydroxyapatite and mesoporous bioactive glass nanoparticles. Starting from a comprehensive rheological assessment, computational-fluid-dynamics-based models were exploited to describe the material flow regime and define the optimal printing process planning. During printing, a gelatin-based bath was exploited to support the deposition of the material, while the gelation of collagen and its further chemical crosslinking with genipin enabled the stabilization of the printed structure, characterized by high shape fidelity. The developed strategy enables the extrusion printing of complex multi-phase systems and the design of high-precision biomimetic scaffolds with great potential for bone tissue engineering.

During the global spread of COVID-19, high demand and limited availability of melt-blown filtration material led to a manufacturing backlog of N95 Filtering Facepiece Respirators (FFRs). This shortfall prompted the search for alternative filter materials that could be quickly mass produced while meeting N95 FFR filtration and breathability performance standards. Here, an unsupported, nonwoven layer of uncharged polystyrene (PS) microfibers was produced via electrospinning that achieves N95 performance standards based on physical parameters (e.g., filter thickness) alone. PS microfibers 3-6 μm in diameter and deposited in an ~5 mm thick filter layer are favorable for use in FFRs, achieving high filtration efficiencies (≥97.5%) and low pressure drops (≤15 mm HO). The PS microfiber filter demonstrates durability upon disinfection with hydroxyl radicals (•OH), maintaining high filtration efficiencies and low pressure drops over six rounds of disinfection. Additionally, the PS microfibers exhibit antibacterial activity (1-log removal of ) and can be modified readily through integration of silver nanoparticles (AgNPs) during electrospinning to enhance their activity (≥3-log removal at 25 wt% AgNP integration). Because of their tunable performance, potential reusability with disinfection, and antimicrobial properties, these electrospun PS microfibers may represent a suitable, alternative filter material for use in N95 FFRs.

Tissue engineered scaffolds are currently being explored to aid in healing and regeneration of non-union fractures in bone. Additionally, albumin has been demonstrated to provide benefits to healing when applied to injury sites. This paper focuses on delivery of calcium modified, bioactive bovine serum albumin (BSA) from a multi-functional polyampholyte polymer scaffold. First, the inherent nonfouling and conjugation properties of the polyampholyte hydrogel were verified to determine the impact of calcium exposure. The polyampholyte hydrogel delivery platform was then assessed with calcium titrations and osteoblast-like cell (MC3T3-E1) adhesion, proliferation, and viability evaluations. Finally, integrin inhibitors were used to identify the binding mechanisms that mediate cell adhesion to the calcium-modified BSA-conjugated hydrogels. An increase in cell adhesion was observed following calcium exposure up to 0.075 M, although this and higher calcium concentrations affected hydrogel stability and cell growth. BSA exposed to 0.05 M calcium and delivered from polyampholyte hydrogels promoted the most promising viable cell adhesion over 7 days. Cell adhesion to the calcium-modified BSA-conjugated hydrogels appeared to be regulated by arginine-glycine-aspartic acid (RGD) and collagen specific integrins. These results demonstrate that the delivery of calcium modified BSA from an implantable polymer scaffold is promising for bone tissue engineering applications.

Polyetheretherketone (PEEK) is a high-performance semi-crystalline thermoplastic polymer with outstanding mechanical properties, high thermal stability, resistance to most common solvents, and good biocompatibility. A high temperature thermally induced phase separation technique was used to produce PEEK foams with controlled foam density from PEEK in 4-phenylphenol (4PPH) solutions. Physical and mechanical properties, foam and bulk density, surface area, and pore morphology of foamed PEEK were characterized and the role of PEEK concentration and cooling rate was investigated. Porous PEEK with densities ranging from 110 to 360 kg/m with elastic moduli and crush strength ranging from 13 to 125 MPa and 0.8 to 7 MPa, respectively, was produced.

In response to the nowadays battle against SARS-CoV-2, we designed a new class of high performant filter media suitable to advance the facemask technology and provide new efficient widespread solutions against virus propagation. By means of the electrospinning technology we developed filter media based on polyvinyl alcohol (PVA) nanofibers doped with AgNPs combining three main performance requirements: high air filtration efficiency to capture nanometer-size particles, low airflow resistance essential to ensure breathability and antimicrobial activity to inactivate aerosolized microorganisms. PVA/AgNPs electrospun nanofibers were produced by electrospinning the dispersion of colloidal silver into the PVA water solution. A widespread physicochemical characterization was addressed to the Ag colloidal suspension. The key functional performances of the electrospun nanofibers were proven by water stability, antibacterial activity, and filtration efficiency and pressure drop measurements performed under conditions representative of facemasks. We assessed a total bacterial depletion associated to a filtering efficiency towards nano-aerosolized particles of 97.7% higher than required by the EN149 standard and a pressure drop in line with FFP1 and FFP2 masks, even at the highest filtration velocity. Such results pave the way to the application of PVA/AgNPs electrospun nanofibers in facemasks as advanced filtering media for protecting against airborne microorganisms.

A technique to fabricate hollow fibers with porous walls via templating from high internal phase emulsions (HIPEs) has been demonstrated. This technique provides an environmentally friendly process alternative to conventional methods for hollow-fiber productions that typically use organic solvents. HIPEs containing acrylate monomers were extruded into an aqueous curing bath. Osmotic pressure effects, manipulated through differences in salt concentration between the curing bath and the aqueous phase within the HIPE were used to control the hollow structures of polyHIPE fibers. The technique was used to produce porous fibers (with millimeter-scale diameters and micronscale pores) having a hollow core (with a diameter of 50%-75% of the fiber diameter). Two potential applications of the hollow fibers were demonstrated. In vitro drug release studies using these hollow fibers show a controlled release profile that is consistent with the microstructure of the porous fiber wall. In addition, the presence of pores in the walls of polyHIPE fibers also enable size-selective loading and separation of functional materials from an external suspension.

The global coronavirus disease 2019 (COVID-19) pandemic has rapidly increased the demand for facemasks as a measure to reduce the rapid spread of the pathogen. Throughout the pandemic, some countries such as Italy had a monthly demand of ca. 90 million facemasks. Domestic mask manufacturers are capable of manufacturing 8 million masks each week, although the demand was 40 million per week during March 2020. This dramatic increase has contributed to a spike in the generation of facemask waste. Facemasks are often manufactured with synthetic materials that are non-biodegradable, and their increased usage and improper disposal are raising environmental concerns. Consequently, there is a strong interest for developing biodegradable facemasks made with for example, renewable nanofibres. A range of natural polymer-based nanofibres has been studied for their potential to be used in air filter applications. This review article examines potential natural polymer-based nanofibres along with their filtration and antimicrobial capabilities for developing biodegradable facemask that will promote a cleaner production.

Injectable sensors can significantly improve the volume of critical biomedical information emerging from the human body in response to injury or disease. Optical oxygen sensors with rapid response times can be achieved by incorporating oxygen-sensitive luminescent molecules within polymeric matrices with suitably high surface area to volume ratios. In this work, electrospraying utilizes these advances to produce conveniently injectable, oxygen sensing particles made up of a core-shell polysulfone-polysulfone structure containing a phosphorescent oxygen-sensitive palladium porphyrin species within the core. Particle morphology is highly dependent on solvent identity and electrospraying parameters; DMF offers the best potential for the creation of uniform, sub-micron particles. Total internal reflection fluorescence (TIRF) microscopy confirms the existence of both core-shell structure and oxygen sensitivity. The dissolved oxygen response time is rapid (<0.30 s), ideal for continuous real-time monitoring of oxygen concentration. The incorporation of Pluronic F-127 surfactant enables efficient dispersion; selection of an appropriate electrospraying solvent (DMF) yields particles readily injected even through a <100 μm diameter needle.

Monomers containing biphenyl moieties were employed to create two sets of covalently crosslinked polymers that displayed noncovalent interactions in their 3-dimensional network. The biphenyls (precursors) used were 2-phenylphenol, 4-phenylphenol and 4,4'-dihydroxybiphenyl, and their acrylated forms were synthesized and named as 2-phenylphenolmonoacrylate (2PPMA), 4-phenylphenolmonoacrylate (4PPMA), and 4,4'-dihydroxybiphenyldiacrylate (44BDA), respectively. These were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) to confirm the successful acrylation reaction. Polymers were synthesized via free radical polymerization reactions with varying crosslinker contents, and their network properties were characterized using swelling studies and compressive modulus tests. Interestingly, swelling studies did not show the expected decreasing swelling ratio with increasing crosslinker content, while compression testing indicated the expected trend of increasing modulus with increasing crosslinking density. The unexpected swelling results are hypothesized to result from the intramolecular interactions between the biphenyl side groups that result in noncovalent crosslinks.

In this work, the development of novel magnetic nanocomposite microparticles (MNMs) via free radical polymerization for their application in the remediation of contaminated water is presented. Acrylated plant-based polyphenols, curcumin multiacrylate (CMA) and quercetin multiacrylate (QMA), were incorporated as functional monomers to create high affinity binding sites for the capture of polychlorinated biphenyls (PCBs), as a model pollutant. The MNMs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, dynamic light scattering, and UV-visible spectroscopy. The affinity of these novel materials for PCB 126 was evaluated and fitted to the nonlinear Langmuir model to determine binding affinities ( ). The results suggest the presence of the polyphenolic moieties enhances the binding affinity for PCB 126, with values comparable to that of antibodies. This demonstrates that these nanocomposite materials have promising potential as environmental remediation adsorbents for harmful contaminants.

Abnormal expression of microRNAs (miRNAs), which are highlyconserved noncoding RNAs that regulate the expression of various genes post transcriptionally to control cellular functions, has been associated with the development of many diseases. In some cases, disease-promoting miRNAs are upregulated, while in other instances disease-suppressive miRNAs are downregulated. To alleviate this imbalanced miRNA expression, either antagomiRs or miRNA mimics can be delivered to cells to inhibit or promote miRNA expression, respectively. Unfortunately, the clinical translation of bare antagomiRs and miRNA mimics has been challenging because nucleic acids are susceptible to nuclease degradation, display unfavorable pharmacokinetics, and cannot passively enter cells. This review emphasizes the challenges associated with miRNA mimic delivery and then discusses the design and implementation of polymer nanocarriers to overcome these challenges. Preclinical efforts are summarized, and a forward-looking perspective on the future clinical translation of polymer nanomaterials as miRNA delivery vehicles is provided.

In the past decade, significant advances in chemistry and manufacturing have enabled the development of increasingly complex and controllable biomaterials. A key innovation is the design of dynamic biomaterials that allow for user-specified, reversible, temporal control over material properties. In this review, we provide an overview of recent advancements in reversible biomaterials, including control of stiffness, chemistry, ligand presentation, and topography. These systems have wide-ranging applications within biomedical engineering, including in vitro disease models and tissue-engineered scaffolds to guide multistep biological processes.

Environmentally responsive nanomaterials have been developed for drug delivery applications, in an effort to target and accumulate therapeutic agents at sites of disease. Within a biological system, these nanomaterials will experience diverse conditions which encompass a variety of solute identities and concentrations. In this study, we developed a new quartz crystal microbalance with dissipation (QCM-D) assay, which enabled the quantitative analysis of nanogel swelling, protein adsorption, and biodegradation in a single experiment. As a proof of concept, we employed this assay to characterize non-degradable and biodegradable poly(acrylamide--methacrylic acid) nanogels. We compared the QCM-D results to those obtained by dynamic light scattering to highlight the advantages and limitations of each method. We detailed our protocol development and practical recommendations, and hope that this study will serve as a guide for others to design application-specific QCM-D assays within the nanomedicine domain.

The versatility and applicability of thermoresponsive polymeric systems have led to great interest and a multitude of publications. Of particular significance, multifunctional poly(-isopropylacrylamide) (PNIPAAm) systems based on PNIPAAm copolymerized with various functional comonomers or based on PNIPAAm combined with nanomaterials exhibiting unique properties. These multifunctional PNIPAAm systems have revolutionized several biomedical fields such as controlled drug delivery, tissue engineering, self-healing materials, and beyond (e.g., environmental treatment applications). Here, we review these multifunctional PNIPAAm-based systems with various cofunctionalities, as well as highlight their unique applications. For instance, addition of hydrophilic or hydrophobic comonomers can allow for polymer lower critical solution temperature modification, which is especially helpful for physiological applications. Natural comonomers with desirable functionalities have also drawn significant attention as pressure surmounts to develop greener, more sustainable materials. Typically, these systems also tend to be more biocompatible and biodegradable and can be advantageous for use in biopharmaceutical and environmental applications. PNIPAAm-based polymeric nanocomposites are reviewed as well, where incorporation of inorganic or carbon nanomaterials creates synergistic systems that tend to be more robust and widely applicable than the individual components.

Change in mechanical property of a degrading adhesive is critical to its performance. However, characterization of degradation behavior is often limited to tracking its mass loss. 4-armed PEG end modified with dopamine (PEG-DA) was used as a model bioadhesive to correlate its change in mass with change in mechanical property. Shear modulus () was calculated based on the mass and average molecular weight between crosslinks of PEG-DA, while the storage modulus () was determined by oscillatory rheometry. decreased slowly within the first week of degradation (10% reduction by week 2), while decreased by 60% during the same period. This large discrepancy is due to the partially disconnected and elastically ineffective PEG polymer, which is trapped within the adhesive network. This resulted in minimal mass change and higher calculated value during the earlier time points. Therefore, tracking mass loss profile alone is inadequate to completely describe the degradation behavior of an adhesive. Additionally, PEG-DA was coated onto magnetoelastic (ME) sensors, and the change in the resonance amplitude of the sensor corresponded well with dry mass loss of PEG-DA. ME sensing provide a non-destructive method to track the mass loss of the coated adhesive.

While many aromatic polyurethane systems suffer from poor hydrolytic stability, more recently proposed aliphatic systems are oxidatively-labile. The use of the renewable monomer glycerol as a more oxidatively-resistant moiety for inclusion in shape memory polymers (SMPs) is demonstrated here. Glycerol-containing SMPs and the amino alcohol control compositions are compared, with accelerated degradation testing displaying increased stability (time to complete mass loss) as a result of the inclusion of glycerol without sacrificing the shape memory, thermal transitions, or the ultralow density achieved with the control compositions. Gravimetric analysis in accelerated oxidative solution indicates that the control will undergo complete mass loss by approximately 18 days, while lower concentrations of glycerol will degrade fully by 30 days and higher concentrations will possess approximately 40% mass at the same time. In real time degradation analysis, high concentrations of glycerol SMPs have 96% mass remaining at 8 months with 88% gel fraction remaining that that time, compared to less than 50% mass for the control samples with 5% gelation. Mechanically, low glycerol-containing SMPs were not robust enough for testing at three months, while high glycerol concentrations displayed increased elastic moduli (133% of virgin materials) and 18% decreased strain to failure. The role of the secondary alcohol, as well as isocyanates, is presented as being a crucial component in controlling degradation; a free secondary alcohol can more rapidly undergo oxidation or dehydration to ultimately yield carboxylic acids, aldehydes, carbon dioxide, and alkenes. Understanding these pathways will improve the utility of medical devices through more precise control of property loss and patient risk management through reduced degradation.

Thiourethane oligomers added to methacrylate matrices improve fracture toughness and reduce polymerization stress. In this study, the oligomers are added to the surface of inorganic fillers in the formulation of resin composites. Systematically varied fillers treated either with the thiourethane or a methacrylate silane control are tested. Thiourethane reduces the rate of polymerization of light-cured composites but does not affect the final degree of conversion (DC). Filler functionalization with thiourethane increases the depth of polymerization, in filler type-dependent fashion. Thiourethane reduces the polymerization stress for all fillers. The findings suggest that this approach results in the same general effects with the addition of thiourethanes directly to the matrix. This is accomplished with a lower overall concentration of thiourethane, and with no prejudice to the handling characteristics of the material.

Cell encapsulation within 3D hydrogels is an attractive approach to develop effective cell-based therapies. However, little is known about how cells respond to the dynamic microenvironment resulting from hydrogel gelation-based cell encapsulation. Here, a tunable biomimetic hydrogel system that possesses alterable gelation kinetics and biologically relevant matrix stiffness is developed to study 3D dynamic cellular responses during encapsulation. Hydrogels are synthesized by cross-linking thiolated hyaluronic acid and thiolated chondroitin sulfate with polyethylene glycol diacrylate under cell-compatible conditions. Hydrogel properties are tailored by altering thiol substitution degrees of glycosaminoglycans or molecular weights of cross-linkers. Encapsulation of human mesenchymal stem cells through hydrogel gelation reveals high cell viability as well as a three-stage gelation-dependent cellular response in real-time focal adhesion kinase (FAK) phosphorylation in live single cells. Furthermore, stiffer hydrogels result in higher equilibrium FAK activity and enhanced actin protrusions. Our results demonstrate the promise of hydrogel-mediated cellular responses during cell encapsulation.