Lab-on-a-Fiber Wearable Multi-Sensor for Monitoring Wound Healing.

Chronic wounds are regarded as a silent epidemic, affecting 1-2% of the population and representing 2-4% of healthcare expenses. The current methods used to assess the wound healing process are based on the visual evaluation of physical parameters. This work aims to design a wearable non-invasive device capable of evaluating three parameters simultaneously: the pH and the levels of glucose and matrix metalloproteinase (MMP) present in the wound exudate. The device is composed of three independent polymer optical fibers functionalized with fluorescent-based sensing chemistries specific to the targeted analytes. Each fiber is characterized in terms of detection sensitivity and selectivity confirming their suitability for monitoring the targeted parameters in ranges relevant to the wound environment. The selectivity and robustness of the multi-sensing device are confirmed with analyses using complex solutions with different pH levels (5, 6, and 7), different concentrations of glucose (1.25, 2.5, and 5 mm), and MMP (1.25, 2.5, and 5 µg mL-1 ). Given the simple set-up, the affordability of the materials used and the possibility of detecting additional parameters relevant to wound healing, such multi-sensing fiber-based devices could pave the way for novel non-invasive wearable tools enabling the assessment of wound healing from the molecular perspective.

Visible light-responsive materials: the (photo)chemistry and applications of donor-acceptor Stenhouse adducts in polymer science.

Donor-acceptor Stenhouse adduct (DASA) photoswitches have gained a lot of attention since their discovery in 2014. Their negative photochromism, visible light absorbance, synthetic tunability, and the large property changes between their photoisomers make them attractive candidates over other commonly used photoswitches for use in materials with responsive or adaptive properties. The development of such materials and their translation into advanced technologies continues to widely impact forefront materials research, and DASAs have thus attracted considerable interest in the field of visible-light responsive molecular switches and dynamic materials. Despite this interest, there have been challenges in understanding their complex behavior in the context of both small molecule studies and materials. Moreover, incorporation of DASAs into polymers can be challenging due to their incompatibility with the conditions for most common polymerization techniques. In this review, therefore, we examine and critically discuss the recent developments and challenges in the field of DASA-containing polymers, aiming at providing a better understanding of the interplay between the properties of both constituents (matrix and photoswitch). The first part summarizes current understanding of DASA design and switching properties. The second section discusses strategies of incorporation of DASAs into polymers, properties of DASA-containing materials, and methods for studying switching of DASAs in materials. We also discuss emerging applications for DASA photoswitches in polymeric materials, ranging from light-responsive drug delivery systems, to photothermal actuators, sensors and photoswitchable surfaces. Last, we summarize the current challenges in the field and venture on the steps required to explore novel systems and expand both the functional properties and the application opportunities of DASA-containing polymers.

Thioflavin-modified molecularly imprinted hydrogel for fluorescent-based non-enzymatic glucose detection in wound exudate.

The concentration of glucose in the body's fluids is an important parameter that can indicate pathological conditions such as the progress of infected wounds. Several wearables and implantable detection approaches have been developed with high selectivity and sensitivity for glucose. However, all of them have drawbacks such as low stability, limited selectivity, and often require complex technology. In this work, we present a fluorescent-based cost-efficient imprinted hydrogel (MIH_GSH) capable of detecting glucose within 30 â€‹min. The imprinting approach allows us to improve the selectivity for glucose, overcoming the low specificity and limited binding efficiency at neutral pH of boronic acid-based detection mechanisms. The binding affinity determined for glucose-MIH_GSH was indeed 6-fold higher than the one determined for the non-imprinted hydrogel with a calculated imprinting factor of 1.7. The limit of detection of MIH_GSH for glucose in artificial wound exudate was calculated as 0.48 â€‹mM at pH 7.4 proving the suitability of the proposed approach to diagnose chronic wounds (ca. 1 â€‹mM). MIH_GSH was compared with a commercial colorimetric assay for the quantification of glucose in wound exudate specimens collected from hospitalized patients. The results obtained with the two methods were statistically similar confirming the robustness of our approach. Importantly, whereas with the colorimetric assay sample preparation was required to limit the interference of the sample background, the fluorescent signal of MIH_GSH was not affected even when used to measure glucose directly in bloody samples. The sensing mechanism here proposed can pave the way for the development of cost-efficient and wearable point-of-care tools capable of monitoring the glucose level in wound exudate enabling the quick assessment of chronic injuries.

pH-responsive silica nanoparticles for the treatment of skin wound infections.

Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic wounds possess an elevated local pH of 8.9 and developed pH-sensitive silica nanoparticles (SiNPs) to achieve a targeted drug release on alkaline wounds and optimized drug utility. Chlorhexidine (CHX), a disinfectant and antiseptic, was loaded into SiNPs as the model drug. The loaded CHX displayed a release 4 - 5 fold higher at pH 8.0 and 8.5 than at pH 6.5, 7.0 and 7.4. CHX-SiNPs furthermore exhibited a distinctive antibacterial activity at pH 8.0 and 8.5 against both Gram-negative and -positive bacterial pathogens, while no cytotoxicity was found according to cell viability analysis. The CHX-SiNPs were further formulated into alginate hydrogels to allow ease of use. The antibacterial efficacy of CHX-SiNPs was then studied with artificial wounds on ex vivo human skin. Treatment with CHX-SiNPs enabled nearly a 4-lg reduction of the viable bacterial cells, and the alginate formulated CHX-SiNPs led to almost a 3-lg reduction compared to the negative controls. The obtained results demonstrated that CHX-SiNPs are capable of efficient pH-triggered drug release, leading to high antibacterial efficacy. Moreover, CHX-SiNPs enlighten clinic potential towards the treatment of chronic wound infections. STATEMENT OF SIGNIFICANCE: A platform for controlled drug release at a relatively high pH value i.e., over 8, was established by tuning the physical structures of silica nanoparticles (SiNPs). Incorporation of chlorhexidine, an antimicrobial agent, into the fabricated SiNPs allowed a distinctive inhibition of bacterial growth at alkaline pHs, but not at acidic pHs. The efficacy of the SiNPs loaded with chlorhexidine in treating wound infections was further validated by utilizing ex vivo human skin samples. The presented work demonstrates clinic potential of employing alkaline pH as a non-invasive stimulus to achieve on-demand delivery of antimicrobials through SiNPs, showcasing a valuable approach to treating bacterial infections on chronic wounds.

Donor-Acceptor Stenhouse Adduct-Polydimethylsiloxane-Conjugates for Enhanced Photoswitching in Bulk Polymers.

Donor-acceptor Stenhouse adducts (DASAs) are a rapidly emerging class of visible light-activated photochromes and DASA-functionalized polymers hold great promise as biocompatible photoresponsive materials. However, the photoswitching performance of DASAs in solid polymer matrices is often low, particularly in materials below their glass transition temperature. To overcome this limitation, DASAs are conjugated to polydimethylsiloxanes which have a glass transition temperature far below room temperature and which can create a mobile molecular environment around the DASAs for achieving more solution-like photoswitching kinetics in bulk polymers. The dispersion of DASAs conjugated to such flexible oligomers into solid polymer matrices allows for more effective and tunable DASA photoswitching in stiff polymers, such as poly(methyl methacrylate), without requiring modifications of the matrix. The photoswitching of conjugates with varying polymer molecular weight, linker type, and architecture is characterized via time-dependent UV-vis spectroscopy in organic solvents and blended into polymethacrylate films. In addition, DASA-functionalized polydimethylsiloxane networks, accessible via the same synthetic route, provide an alternative solution for achieving fast and efficient DASA photoswitching in the bulk owing to their intrinsic softness and flexibility. These findings may contribute to the development of DASA-functionalized materials with better tunable, more effective, and more reversible modulation of their optical properties.

Metal-Modified Montmorillonite as Plasmonic Microstructure for Direct Protein Detection.

Thanks to its negative surface charge and high swelling behavior, montmorillonite (MMT) has been widely used to design hybrid materials for applications in metal ion adsorption, drug delivery, or antibacterial substrates. The changes in photophysical and photochemical properties observed when fluorophores interact with MMT make these hybrid materials attractive for designing novel optical sensors. Sensor technology is making huge strides forward, achieving high sensitivity and selectivity, but the fabrication of the sensing platform is often time-consuming and requires expensive chemicals and facilities. Here, we synthesized metal-modified MMT particles suitable for the bio-sensing of self-fluorescent biomolecules. The fluorescent enhancement achieved by combining clay minerals and plasmonic effect was exploited to improve the sensitivity of the fluorescence-based detection mechanism. As proof of concept, we showed that the signal of fluorescein isothiocyanate can be harvested by a factor of 60 using silver-modified MMT, while bovine serum albumin was successfully detected at 1.9 µg/mL. Furthermore, we demonstrated the versatility of the proposed hybrid materials by exploiting their plasmonic properties to develop liquid label-free detection systems. Our results on the signal enhancement achieved using metal-modified MMT will allow the development of highly sensitive, easily fabricated, and cost-efficient fluorescent- and plasmonic-based detection methods for biomolecules.

Promoting the Furan Ring-Opening Reaction to Access New Donor-Acceptor Stenhouse Adducts with Hexafluoroisopropanol.

Donor-acceptor Stenhouse adducts (DASAs) are visible-light-responsive photoswitches with a variety of emerging applications in photoresponsive materials. Their two-step modular synthesis, centered on the nucleophilic ring opening of an activated furan, makes DASAs readily accessible. However, the use of less reactive donors or acceptors renders the process slow and low yielding, which has limited their development. We demonstrate here that 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) promotes the ring-opening reaction and stabilizes the open isomer, allowing greatly reduced reaction times and increased yields for known derivatives. In addition, it provides access to previously unattainable DASA-based photoswitches and DASA-polymer conjugates. The role of HFIP and the photochromic properties of a set of new DASAs is probed using a combination of 1 H NMR and UV/Vis spectroscopy. The use of sterically hindered, electron-poor amines enabled the dark equilibrium to be decoupled from closed-isomer half-lives for the first time.

Changes in Optical Properties upon Dye-Clay Interaction: Experimental Evaluation and Applications.

The development of hybrid materials with unique optical properties has been a challenge for the creation of high-performance composites. The improved photophysical and photochemical properties observed when fluorophores interact with clay minerals, as well as the accessibility and easy handling of such natural materials, make these nanocomposites attractive for designing novel optical hybrid materials. Here, we present a method of promoting this interaction by conjugating dyes with chitosan. The fluorescent properties of conjugated dye-montmorillonite (MMT) hybrids were similar to those of free dye-MMT hybrids. Moreover, we analyzed the relationship between the changes in optical properties of the dye interacting with clay and its structure and defined the physical and chemical mechanisms that take place upon dye-MMT interactions leading to the optical changes. Conjugation to chitosan additionally ensures stable adsorption on clay nanoplatelets due to the strong electrostatic interaction between chitosan and clay. This work thus provides a method to facilitate the design of solid-state hybrid nanomaterials relevant for potential applications in bioimaging, sensing and optical purposes.

Experimental determination and ray-tracing simulation of bending losses in melt-spun polymer optical fibres.

The damping properties and specifically the bend losses of polymer optical fibres (POFs) have so far only been documented by experimental work, investigating bending parameters such as bending radius, length, and distance of the bends. Even though damping mechanisms and causes are well-known, no simple, generally valid formula exists. Here, a simulation technique is shown that allows producing an optical model for any bending geometries of melt-spun polymer optical fibres. The developed model takes all relevant loss mechanisms into account, especially regarding the scattering losses at the interface of core and cladding as well as those of the cladding-air interface. The latter is caused by interfacial roughness for which experimental data have been obtained by atomic force microscopy measurements. To show the validity of the simulation, the model is compared to experimental results for several fibres and a variety of geometries. The variance between model and experimental data is low (S < 4.6%). The model not only contributes to improving the understanding of the optical properties of POFs, but it also has direct applicability to the design of photonic textile sensors for medicine, where the fibres are incorporated with small bending radii.

Facile Fabrication of Microfluidic Chips for 3D Hydrodynamic Focusing and Wet Spinning of Polymeric Fibers.

Microfluidic wet spinning has gained increasing interest in recent years as an alternative to conventional wet spinning by offering higher control in fiber morphology and a gateway for the development of multi-material fibers. Conventionally, microfluidic chips used to create such fibers are fabricated by soft lithography, a method that requires both time and investment in necessary cleanroom facilities. Recently, additive manufacturing techniques were investigated for rapid and cost-efficient prototyping. However, these microfluidic devices are not yet matching the resolutions and tolerances offered by soft lithography. Herein, we report a facile and rapid method using selected arrays of hypodermic needles as templates within a silicone elastomer matrix. The produced microfluidic spinnerets display co-axially aligned circular channels. By simulation and flow experiments, we prove that these devices can maintain laminar flow conditions and achieve precise 3D hydrodynamic focusing. The devices were tested with a commercial polyurethane formulation to demonstrate that fibers with desired morphologies can be produced by varying the degree of hydrodynamic focusing. Thanks to the adaptability of this concept to different microfluidic spinneret designs-as well as to its transparency, ease of fabrication, and cost-efficient procedure-this device sets the ground for transferring microfluidic wet spinning towards industrial textile settings.

Pyranine-Modified Amphiphilic Polymer Conetworks as Fluorescent Ratiometric pH Sensors.

The fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonate (pyranine) combines high photostability with ratiometric pH detection in the physiological range, making it a prime candidate for optical sensors in biomedical applications, such as pH-based chronic wound monitoring. However, pyranine's high water solubility and the difficulty of covalent attachment pose severe limitations in terms of leaching from sensor matrices. Herein, pyranine-modified nanophase-separated amphiphilic polymer conetworks (APCNs) are reported as fluorescent ratiometric pH sensors. The thin, freestanding APCN membranes composed of one hydrophilic and one hydrophobic polymer provide an optically transparent, flexible, and stable ideal matrix that enables contact between dye and aqueous environment. An active ester-based conjugation approach results in a highly homogeneous and stable pyranine modification of the APCN's hydrophilic phase. This concept effectively solves the leaching challenge for pyranine without compromising its functionality, which is demonstrated by ratiometric pH detection in the range of pH 5-9.

Wavelength-Selective Light-Responsive DASA-Functionalized Polymersome Nanoreactors.

Transient activation of biochemical reactions by visible light and subsequent return to the inactive state in the absence of light is an essential feature of the biochemical processes in photoreceptor cells. To mimic such light-responsiveness with artificial nanosystems, polymersome nanoreactors were developed that can be switched on by visible light and self-revert fast in the dark at room temperature to their inactive state. Donor-acceptor Stenhouse adducts (DASAs), with their ability to isomerize upon irradiation with visible light, were employed to change the permeability of polymersome membranes by switching polarity from a nonpolar triene-enol form to a cyclopentenone with increased polarity. To this end, amphiphilic block copolymers containing poly(pentafluorophenyl methacrylate) in their hydrophobic block were synthesized by reversible addition-fragmentation chain-transfer (RAFT) radical polymerization and functionalized either with a DASA that is based on Meldrum's acid or with a novel fast-switching pyrazolone-based DASA. These polymers were self-assembled into vesicles. Release of hydrophilic payload could be triggered by light and stopped as soon as the light was turned off. The encapsulation of enzymes yielded photoresponsive nanoreactors that catalyzed reactions only if they were irradiated with light. A mixture of polymersome nanoreactors, one that switches in green light, the other switching in red light, permitted specific control of the individual reactions of a reaction cascade in one pot by irradiation with varied wavelengths, thus enabling light-controlled wavelength-selective catalysis. The DASA-based nanoreactors demonstrate the potential of DASAs to switch permeability of membranes and could find application to switch reactions on and off, on demand, e.g., in microfluidics or in drug delivery.

POF-yarn weaves: controlling the light out-coupling of wearable phototherapy devices.

Neonatal jaundice (hyperbilirubinaemia) is common in neonates and, often, intensive blue-light phototherapy is required to prevent long-term effects. A photonic textile can overcome three major incubator-related concerns: Insulation of the neonate, human contact, and usage restraints. This paper describes the development of a homogeneous luminous textile from polymer optical fibres to use as a wearable, long-term phototherapy device. The bend out-coupling of light from the POFs was related to the weave production, e.g. weave pattern and yarn densities. Comfort, determined by friction against a skin model and breathability, was investigated additionally. Our textile is the first example of phototherapeutic clothing that is produced sans post-processing allowing for faster commercial production.

Body-monitoring with photonic textiles: a reflective heartbeat sensor based on polymer optical fibres.

Knowledge of an individual's skin condition is important for pressure ulcer prevention. Detecting early changes in skin through perfusion, oxygen saturation values, and pressure on tissue and subsequent therapeutic intervention could increase patients' quality of life drastically. However, most existing sensing options create additional risk of ulcer development due to further pressure on and chafing of the skin. Here, as a first component, we present a flexible, photonic textile-based sensor for the continuous monitoring of the heartbeat and blood flow. Polymer optical fibres (POFs) are melt-spun continuously and characterized optically and mechanically before being embroidered. The resulting sensor shows flexibility when embroidered into a moisture-wicking fabric, and withstands disinfection with hospital-type laundry cycles. Additionally, the new sensor textile shows a lower static coefficient of friction (COF) than conventionally used bedsheets in both dry and sweaty conditions versus a skin model. Finally, we demonstrate the functionality of our sensor by measuring the heartbeat at the forehead in reflection mode and comparing it with commercial finger photoplethysmography for several subjects. Our results will allow the development of flexible, individualized, and fully textile-integrated wearable sensors for sensitive skin conditions and general long-term monitoring of patients with risk for pressure ulcer.

Visible Light-Responsive DASA-Polymer Conjugates.

A modular synthesis of Donor-Acceptor Stenhouse Adduct (DASA) polymer conjugates is described. Pentafluorophenyl-ester chemistry is employed to incorporate aromatic amines into acrylate and methacrylate copolymers, which are subsequently coupled with activated furans to generate polymers bearing a range of DASA units in a modular manner. The effect of polymer glass transition temperature on switching kinetics is studied, showing dramatic rate enhancements in going from a glassy to a rubbery matrix. Moreover, tuning the DASA absorption profile allows for selective switching, as demonstrated by ternary photopatterning, with potential applications in rewriteable data storage.

Polylactide/Montmorillonite Hybrid Latex as a Barrier Coating for Paper Applications.

We developed a paper coating for the potential application in food packaging based on polylactide and montmorillonite. It is applied to the paper in the form of a stable, water-based latex with a solid content of 25⁻28 wt %. The latex is prepared from a commercially available polylactide, surfactants, montmorillonite, a plasticizer, chloroform (to be removed later) and water by an emulsion/solvent evaporation procedure. This coating formulation is applied to the paper substrate by bar-coating, followed by hot-pressing at 150 °C. The coated papers achieved up to an 85% improvement in water vapor transmission rates when compared to the pristine papers. The coating latex is prepared from inexpensive materials and can be used for a solvent-free coating process. In addition, the ingredients of the latex are non-toxic; thus, the coated papers can be safely used for food packaging.

Incorporation of a FRET dye pair into mesoporous materials: a comparison of fluorescence spectra, FRET activity and dye accessibility.

Fluorescein and rhodamine B modified mesoporous silica particles were synthesized by post-grafting and co-condensation approaches. The materials exhibited different pore size distributions, particle shapes and sizes. The materials were characterized by nitrogen sorption, scanning electron microscopy and fluorescence spectroscopy. The Förster resonance energy transfer between the selected dye pair was explored for the different materials by exposure to various concentrations of gaseous ammonia. A logarithmic increase in rhodamine B emission with increasing ammonia concentration was observed for both post-grafted and co-condensed materials. The dye accessibility by ammonia gas in the silica framework of mesoporous materials was evaluated by using a flow cell gas sensor setup built in-house. Response to ammonia gas and recovery with nitrogen gas are explained by comparing the structure properties and dye loading of the materials. The post-grafted dye modified silica showed better performance in terms of reversibility and recovery.

Ellipsoid-shaped superparamagnetic nanoclusters through emulsion electrospinning.

Ellipsoid-shaped nanoclusters composed of single superparamagnetic nanoparticles can be generated by emulsion electrospinning. Stretching and subsequent solvent evaporation of iron oxide loaded emulsion droplets during the emulsion electrospinning process enables the creation of such structures embedded in polymer nanofibers. Dissolution of the polymer fibers yields an aqueous dispersion of the inorganic clusters which are the first example of ellipsoid-shaped superparamagnetic nanoclusters with a high saturation magnetization (∼47 emu g(-1)).