ACS Applied Bio Materials

Silicones are elastomers that have a wide variety of uses, including biomedical applications such as the coating of biomedical devices and as implants. Soft silicones with mechanical properties similar to those of biological tissues have particularly gained use as substrates for cell culture in mechanobiology studies. In this context, it would be desirable to be able to alter their surface mechanical properties with a relatively simple physical treatment. While deep ultraviolet (deep UV) or ultraviolet C (UV-C) treatment has been previously used as a surface treatment method for stiffer silicones formulations, the effect of this treatment on soft silicones relevant for mechanobiology applications is still uncharacterized. We first used nanoindentation to determine the Youngs modulus of two types of soft silicones, Qgel and GEL-8100/Syl (GEL-8100 with Sylgard-184 crosslinker), both with initial moduli in the kilopascal range. We show that nanoindentation in the presence of 1% sodium dodecyl sulfate avoids adhesion between the nanoindentation glass probe and the soft silicones. After deep UV exposure in the presence of air, nanoindentation revealed that the apparent Youngs moduli of the soft silicones Qgel and GEL-8100/Syl increased by 70% and 33%, respectively. The bulk rheology of the soft silicones were not affected, suggesting that this corresponds to a surface stiffening effect with a topical stiffening of at least several hundred kilopascals. Energy-dispersive X-ray spectroscopy results show an increase in the mole fraction of oxygen, consistent with oxidation of the surface. Attenuated Total Reflectance Fourier-Transform Infrared spectra show evidence of Si-OH group formation in GEL-8100/Syl and silicon sub-oxide formation in Qgel. Consistent with this, water contact angle measurements show enhanced hydrophilicity after deep UV treatment. Our results have implications for using soft silicones as substrates in mechanobiology studies and in processes where deep UV light is used in the surface treatment of soft silicones.

Vocal fold (VF) fibrosis is a major cause of persistent dysphonia due to excessive extracellular matrix deposition and tissue stiffening that disrupt normal vocal fold vibration. Current treatment approaches are limited by the need for repeated local injections and inadequate long-term therapeutic control. Pirfenidone (PFD), an FDA-approved antifibrotic agent, has demonstrated potential for reducing fibrosis; however, its short half-life and systemic adverse effects limit conventional administration strategies. In this study, we developed a sustained and near-infrared (NIR)-responsive local delivery platform by integrating PFD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles into biodegradable PLGA implants for dose-controllable antifibrotic delivery. PFD-loaded PLGA nanoparticles were fabricated using an oil-in-water emulsion solvent evaporation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Nanoparticles with small, medium, and large hydrodynamic diameters were generated to evaluate the effect of particle size on release behavior. Gold nanorods (AuNRs) were incorporated to enable photothermal NIR-triggered release enhancement. The nanoparticles were subsequently loaded into non-porous PLGA (90:10) implants and evaluated for long-term in vitro release under physiological conditions with and without pulsed 1064 nm laser irradiation. The nanoparticle-loaded implants demonstrated sustained PFD release for over 190 days with minimal initial burst release (<2.5%). NIR irradiation enhanced PFD release compared with non-irradiated controls across all nanoparticle sizes. Smaller nanoparticles produced greater cumulative release than medium and large nanoparticles due to shorter diffusion pathways and larger surface-area-to-volume ratios. Prior to implant fracture, cumulative PFD release reached approximately 20.2%, 14.8%, and 12.3% of total loading for small, medium, and large nanoparticle groups under 2-min irradiation conditions, respectively. Dialysis membrane studies further demonstrated that the PLGA capsule acted as an additional diffusion barrier that substantially prolonged release compared with nanoparticles alone. Overall, this study demonstrates a hybrid nanoparticle-in-implant strategy capable of providing sustained and irradiation-enhanced local PFD delivery with tunable release characteristics. These findings support the potential of biodegradable, dose-controllable implant systems for long-term management of vocal fold fibrosis while reducing the need for repeated interventions.

Bacterial biofilms on indwelling medical devices is a major driver of healthcare-associated infection despite significant advances in antifouling surface engineering, suggesting that laboratory antibacterial performance does not fully capture the determinants of clinical colonization. Here we show that adherent immune cells constitute a previously underappreciated conditioning layer that promotes biofilm formation on otherwise antifouling biomaterials. Pre-exposure of clinically used substrates to macrophages, monocytes, neutrophils or human peripheral blood cells markedly increased Staphylococcus aureus and Escherichia coli adhesion and aggregation. These studies also reveal that immune cells promote biofilms even after cell death with cellular debris acting as a conditioning agent. We demonstrate that reactive-oxygen-species amplification by incorporating bismuth telluride into a silicone composite converts adherent immune cells from passive conditioning agents into active bactericidal effectors. We note that this antimicrobial composite confers durable antibacterial protection across early, delayed and late infection time points in a murine implantation model. Together, these findings introduce a class of immune-coupled antibacterial materials as an alternative to the current antifouling paradigm.

The inaccessibility of intracellular bacteria has long rendered the treatment of Staphylococcus aureus infections an challenge. Studies have demonstrated that the extracellular injection system PVC can accurately deliver proteins into cells, which would not need small molecules, and enables effective intracellular delivery of antimicrobial peptides for treatment. Accordingly, we selected antimicrobial peptides including Cecropin, LL37 and Indolicidin that possess potent bactericidal activity, and established the Directed Antimicrobial Assault platform (DAAT) by leveraging the intracellular delivery capacity of PVC. DAAT Cecropin, DAAT LL37 and DAAT Indolicidin inhibited intracellular bacteria in a dose-dependent manner, with DAAT LL37 reaching 86.76% inhibition; after 72 h of treatment, viable-cell numbers reduse to 66--82-fold those of the control. Tail-fibre retargeting enabled direct extracellular S. aureus killing, while combined DAAT therapy promoted wound healing in mice. These findings expand the utility of PVC-derived nanosyringes and establish DAAT as a modular platform for intracellular antimicrobial peptide therapy.

This work describes a new approach for rapid and reproducible formulation of drug loaded biodegradable nanoparticles based on polyester copolymers, including poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) and poly(caprolactone)-poly(ethylene glycol) (PCL-PEG). The new approach, termed Solvent-free Nanoparticle Assembly Protocol (SNAP), carries several advantages over conventional polyester formulation strategies, including very rapid formulation (minutes) and the ability to use nanoparticles immediately without lengthy solvent evaporation or washing steps. Altering polyester molecular weight and concentration, alongside the introduction of specific functional groups yielded precise control of nanoparticle properties, including size, shape, surface charge, drug release and loading. We examined loading of multiple therapeutic compounds, including diclofenac, loperamide, bortezomib, CT179, panobinostat, docetaxel, methotrexate, and camptothecin. The SNAP protocol facilitated the rapid production of stable, drug-loaded nanoparticles with a narrow size distribution and generally good drug loading. Using Fluorescence Resonance Energy Transfer (FRET) and size exclusion chromatography (SEC) with a focus on the model agent Rhodamine B, we were able to carefully examine stability of the nanoparticle and assess the distribution of small molecules within the polymer as well as nanoparticle stability. In vivo evaluation of fluorescently labeled nanoparticles using real-time, intravital microscopy showed that, after direct administration to cerebrospinal fluid (CSF) via the intrathecal cisterna magna (IT-CM) route, the dynamic accumulation of nanoparticles within the perivascular space (PVS) depends on the size of the vessel that is imaged. Nanoparticles accumulated steadily within the PVS of large vessels, while accumulating more slowly and exhibiting clearance from medium-sized and smaller vessels over the course of several hours. In sum, these studies present a new platform for facile production of polyester nanoparticles, demonstrate their ability to encapsulate a variety of hydrophobic small molecules, and expand our knowledge on the development of nanocarriers for intrathecal administration. Taken together, these data open new opportunities for development safer and more effective nanoparticle-based therapies.

Controlled drug delivery systems have important implications in many therapeutic applications to improve patient health, but it remains challenging to deliver therapeutics to specific target sites while being released at controlled rates to minimize the off-target accumulation. Here, we report a drug (e.g., vancomycin)-modulating other drug release strategies in human serum albumin (HSA)-based nanoparticles (NPs) to achieve multiple drug encapsulation and controlled release of drugs. Without external stimuli but only with water, the release kinetics of drugs such as sulfasalazine and epidermal growth factor can be modulated by adding vancomycin. The mechanistic study suggests that the release kinetics are related to the secondary structure of albumin through the interactions between drugs and HSA. Our strategy achieved controlled drug delivery through modulating the secondary structure of albumin with a water-soluble drug as a modulator, which provides a promising way to simultaneously deliver multiple drugs while releasing in a predicted and sustained manner.

Most antimicrobial drug candidates currently in development are derivatives of established antibiotic classes. In contrast, antimicrobial heteroatom-doped carbon quantum dot (CQD) nanoparticles vastly differ from their chemical antibiotic counterparts and exhibit potent antibacterial activity and favourable biocompatibility, representing a promising alternative strategy, particularly for topical applications. Here, we report the incorporation of cobalt-doped carbon quantum dots (Co-CQDs) into injectable, biocompatible hydrogels capable of both sensing pH and eliminating bacteria. Ultrasmall Co-CQDs demonstrated broad-spectrum activity against gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PAO1), mediated by membrane hyperpolarisation and reactive oxygen species (ROS) induced membrane damage. The particles showed negligible effect on primary fibroblast and endothelial cell viability at concentrations that were bactericidal to MRSA. Polymeric hydrogels were fabricated via electrospinning of chitosan, polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA) polymer blends incorporating Co-CQD and pH-responsive HPTS particles. This approach provided accurate measurement of environmental pH within the physiological range observed across healthy and chronic wounds. In vivo, the injectable hydrogels exhibited robust antimicrobial efficacy against MRSA without impairing wound closure relative to untreated controls, while also reducing inflammatory immune responses in infected tissues. Collectively, these findings demonstrate the potential of ultrasmall metal-doped CQDs for infection control and their integration into 3D matrices as multifunctional theragnostic platforms.

Chronic wounds such as diabetic foot ulcers are typically more alkaline than healing wounds, making wound pH a valuable diagnostic and prognostic marker. However, point-of-care pH monitoring remains limited by the availability of point-of-care wound pH sensing systems that offer quantitative pH determination, low toxicity, and small portable detectors. Here, we report a colorimetric pH-sensing wound dressing that enables in situ pH detection using a conventional smartphone camera. The anionic pH-sensitive dye HPTS was loaded onto cationic microparticles and embedded within a calcium-crosslinked alginate hydrogel. Across the clinically relevant range of pH 6.0-9.0, increasing pH produced a progressively more intense yellow coloration, quantified through the blue channel of smartphone-acquired RGB images. The dressing displayed a strong, rapid, and reversible signal in vitro with low dye release. In a full-thickness excisional wound model in mice, wound pH changes were detected in vivo. The combination of a pH-sensitive colorimetric hydrogel with a conventional smartphone detector offers accessible wound pH monitoring at the point-of-care.

Conducting polymers are widely used in bioelectronic interfaces because of their mixed ionic-electronic conductivity, mechanical compliance, and compatibility with biological systems. However, their electrochemically driven structural dynamics have received little attention as a mechanism for mechanical cell stimulation. Here, we show that electrochemical actuation of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) generates mechanical cues capable of activating endogenous mechanosensitive pathways in HEK293T cells. Transparent PEDOT:PSS films deposited on ITO exhibited a heterogeneous granular morphology and underwent potential-dependent microscopic deformation during electrochemical modulation. Direct optical tracking revealed displacement of the polymer boundary, with structural changes occurring preferentially in polymer-dense regions and propagating toward the film edge. When HEK293T cells were cultured directly on PEDOT:PSS, repeated electrochemical stimulation at -240 mV produced reproducible intracellular Ca2+ responses. Pharmacological inhibition with GsMTx4 attenuated the calcium response, whereas blockade of voltage-gated sodium channels with tetrodotoxin largely preserved it, supporting the involvement of mechanosensitive pathways in the cellular response. These findings identify PEDOT:PSS as an electromechanical biointerface in which electrochemical modulation can introduce a mechanical component alongside the established electrical function of the interface. This mechanical contribution should therefore be considered when interpreting cellular responses to conducting polymer- based electrical stimulation and provides a basis for engineering bioelectronic interfaces that deliberately couple electrical control with mechanotransduction.

Liquid crystalline mesophases exhibit structurally programmable internal architectures that enable co-loading of chemically orthogonal molecules within a single composite material. Realizing the potential of these materials for drug delivery requires a quantitative understanding of how tuning the composition affects internal mesophase architecture and consequently performance metrics such as payload release. Here, Flash NanoPrecipitation with hydrophobic ion pairing is used to prepare nanocarriers containing liquid crystalline mesophases co-encapsulating two compounds from widely different chemical classes: hydrophilic polymyxin B (logP -6) with one of four hydrophobic co-core materials (logP 7-11), achieving >75% encapsulation efficiency and up to 32% and 50% mass loadings for polymyxin and co-core. Synchrotron SAXS is used to quantify characteristic mesophase repeat spacing, which is found to be tunable as a function of composition. A strong correlation between d-spacing and polymyxin release rate is presented. Co-core chemistry and weight fraction jointly govern mesophase architecture, and repeat distance emerges as a structural metric linking these to the hydrophilic payload release kinetics. Mucus diffusivity and antibacterial efficacy are assessed as independent performance metrics, and results corroborate the release behavior. These findings establish a quantitative framework connecting material composition, mesophase architecture, and functional performance that can be applied toward rational co-formulation design. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/734853v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1d722eborg.highwire.dtl.DTLVardef@135adb7org.highwire.dtl.DTLVardef@11fe29eorg.highwire.dtl.DTLVardef@571165_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOToC Graphic TextC_FLOATNO Flash NanoPrecipitation yields liquid crystalline nanocarriers co-encapsulating with high efficiency payloads with widely distinct physicochemical properties. Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures. C_FIG

Three-dimensional (3D) spheroid culture provides a physiologically relevant alternative to conventional two-dimensional culture, but reliable spheroid formation in microwells depends on limiting cell-substrate adhesion. Pluronic F127 is an amphiphilic triblock copolymer that forms a hydrated surface layer, reducing protein adsorption. Here, we evaluated whether this intrinsic anti-fouling property could restore an anti-adhesive surface in used microwell plates to promote spheroid formation. Using chondrogenic ATDC5 and pancreatic {beta}-cell INS-1 cells, we characterized spheroid assembly kinetics, F127 cytotoxicity, surface hydrophilicity, protein adsorption, and spheroid morphology including size and shape factor. Both cell types formed compact spheroids within 24 hours on commercial anti-adhesive microwells. F127 coating markedly reduced water contact angle and protein adsorption, confirming increased surface hydrophilicity and reduced protein fouling. In microwells stripped of their original surface coating, F127 coating amounts of approximately 0.011-0.045 mg/cm2 consistently promoted spheroid formation across both cell types. Soluble F127 concentrations were confirmed to be non-cytotoxic up to 0.625% (w/v), while even complete dissolution of the highest tested coating amount would correspond to only 0.025% (w/v) F127. This simple, reproducible, and low-cost surface-modification strategy may provide an accessible approach for re-functionalizing microwell platforms for 3D cell culture.

This study reports a brand-new continuous-wave-excited (CW-excited) two-photon fluorescence emission mechanism in indocyanine green (ICG), an organic fluorescent dye widely used in clinical practice. This mechanism is based on the excited state absorption (ESA) process of the first singlet excited state. Intramolecular electrons sequentially absorb two photons to reach a high-energy singlet excited state, followed by direct radiative transition to the ground state to generate fluorescence. The entire process is exclusively mediated by singlet states. We further summarize the essential requirements for organic dyes to realize this luminescence mechanism. First, the dye must possess at least two well-separated singlet excited states with distinct energies, corresponding to two absorption peaks at different wavelengths in the absorption spectrum. The wavelength of the high-energy singlet excited state is about half that of the first singlet excited state. Second, the peak in the absorption spectrum corresponding to the transition from the ground state to the first singlet excited state has a sufficiently large molar extinction coefficient. Third, the first singlet excited state exhibits the capability of ESA. Fourth, electrons at the high-energy singlet excited state can directly transit to the ground state and emit fluorescence. We validated this mechanism in a variety of organic dyes satisfying the above conditions, confirming its universality. Using CW laser as the excitation source, we achieved two-photon fluorescence imaging of mouse cerebral blood vessels at a depth of 400 m, which clearly resolves three-dimensional vascular networks with high resolution. We also performed two-photon fluorescence imaging on human gastric cancer tissue samples at a depth of around 150 m, which provides a low-cost strategy for clinicians to rapidly acquire high-contrast tumor tissue images.

Parkinsons Disease (PD) is the second-most prevalent neurodegenerative disease, often characterized by neural motor dysfunction, oxidative stress, and dopamine receptor malfunction leading to improper dopamine levels in the system. DNA tetrahedron nanostructures are a promising drug delivery agent due to their biocompatibility and properties of controlled and sustained release. In this study we evaluated the potential of using TD-mediated Levodopa delivery for a MPTP induced Parkinsons Disease model in Zebrafish larvae. The induction of Parkinsonism led to morphological behaviour changes like the presence of tremors, erratic swimming behaviour, latency, and reduced locomotor activity, even elevated reactive oxygen species (ROS) and apoptosis was observed. These effects and symptoms were alleviated when the larvae were treated using TD:Levodopa conjugates, particularly at the 1:100 ratio. At the molecular level, genes like TH, DAT, SOX2, PARKIN and apoptotic genes like BCL2 and caspases showed alteration in expression in the Parkinsonism model and post treatment was induced. This highlights the potential of using DNA nanocages as a novel drug delivery agent as therapeutic strategy for Parkinsons disease. TOCDopamine loaded DNA nanocages with the capacity to overcome biological barriers for release of dopamine with neuroprotection activity in Parkinsons disease model of zebrafish. O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/742731v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@40d78forg.highwire.dtl.DTLVardef@107f59forg.highwire.dtl.DTLVardef@18ea275org.highwire.dtl.DTLVardef@14bc089_HPS_FORMAT_FIGEXP M_FIG C_FIG

The term nanobubble (NB) includes a wide range of gas core, submicron particles. A subgroup of NBs consists of phospholipid-shelled (or coated) nanoparticles stabilizing a perfluorocarbon gas core which have gained recent interest as ultrasound (US) contrast agents. Several methods are available to produce coated NBs. Among these, amalgamation driven self-assembly has been the most utilized. Amalgamation (also referred to as mechanical agitation) is a simple technique currently used for production of commercial and clinically relevant microbubble suspensions. When combined with size-isolation steps, it can also generate submicron NB suspensions with a narrow size distribution. While this technique has been used extensively, no prior work has systematically examined the critical manufacturing parameters needed to produce the optimal coated NB formulation. In this work, we investigate how the precursor lipid dispersion, perfluorocarbon gas to lipid ratio, and pressurized size isolation affect the formation and size isolation of stable, uniform NBs. Results show that the precursor lipid dispersions exhibiting a monomodal size distribution produced the most stable NBs. Additionally, perfluorocarbon volume in excess of lipid dispersion volume is required to form high concentration, stable NBs. Finally, pressurized size isolation resulted in high concentration, US stable NBs. These findings establish the understanding of the key process parameters which affect uniform size and stable NB production via mechanical amalgamation.

Potent antineoplastics, such as afatinib and freebase doxorubicin, are associated with systemic toxicity. To address this issue, we developed a carrier that releases drugs, including afatinib and doxorubicin, specifically at the focus of low-intensity ultrasound. This remotely triggered and focal approach enables the release of drugs specifically at the ultrasound focus, thus mitigating undesirable off-target effects, and at concentrations governed by the duration of the applied ultrasound. We produced ultrasound-sensitive microdroplets with high encapsulation efficiencies (39.6% for afatinib and 46.6% for doxorubicin). The microdroplets consist of an ultrasound-sensitive drug delivery system based on a methoxy poly(ethylene glycol)-poly(D, L-lactide) diblock copolymer (mPEG-PDLLA) and perfluorooctyl bromide (PFOB). Antineoplastic agents were encapsulated within these microdroplets via co-evaporation during particle synthesis. The microdroplets released doxorubicin and afatinib in an ultrasound-pressure-dependent manner, with fitted half-maximal release pressures (P50) of 0.61 MPa and 0.72 MPa, respectively. Together, the effective encapsulation of hydrophobic antineoplastic agents and the dose-dependent ultrasound-triggered release provide a new method for targeted drug delivery and a foundation for future targeted chemotherapies.

Foreign body response is a common yet serious challenge for biomedical implants. It can trigger inflammation and eventually lead to the formation of a fibrotic capsule, which compromises device function. Although significant efforts have been made to develop antifibrotic surface coatings for implantable materials, developing broadly applicable solutions remains challenging due to the diversity of materials used in biomedical implants. Here, we propose a simple and versatile strategy to develop antifibrotic coatings for biomedical implants. Photoreactive benzophenone groups are incorporated into designer polymers to enable covalent attachment to various substrates. The effect of benzophenone group density within polymer chains on surface coating efficiency was investigated, and an optimal BP incorporation ratio was identified. Polymers incorporating varying ratios of an anti-fibrotic small molecule and anti-fouling zwitterionic moieties were synthesized and successfully attached to silicone implants. In vivo evaluation of these implants in C57BL/6 mice identified an optimized polymer composition that reduced fibrotic capsule thickness by around 60%. Coating of commercial medical catheters with this optimized polymer reduced collagen deposition by over 3.5-fold following 4 weeks of implantation in the peritoneal space of C57BL/6 mice. Finally, we demonstrated that the optimized polymer coating can be readily applied to a variety of commonly used biomedical materials using this straightforward method, highlighting the versatility of the approach. This work provides a facile and broadly applicable strategy for developing antifibrotic coatings, which has the potential to expand the design of surface modifications aimed at improving the performance of biomedical implants.

Oral routes of delivery are logistically simple and enables easy administration of therapeutics. However, oral delivery of proteins is still challenging due to the proteolytic environment within the gastrointestinal (GI) tract. To protect protein cargo from degradation, polymer encapsulation is commonly used, and when it is combined with cell-free gene expression (CFE) approaches that enable the rapid and flexible production of proteins, it potentially allows for on-demand production of protein therapeutics. Here, we investigated the suitability of chitosan coated alginate (Alg/Cht) microcapsules for encapsulation of proteins and CFE lysates for oral delivery. We show that CFE lysates can produce functional mCherry, a model fluorescent protein, in the presence of alginate polymers, although direct contact with chitosan did inhibit protein synthesis. We encapsulated CFE lysates or purified mCherry protein into alginate cores before crosslinking them using internal gelation techniques and coating with chitosan to test their protective capacity for oral delivery. Alg/Cht microcapsules protected mCherry protein cargo from degradation in simulated human gastric fluids and mouse gastric extracts and facilitated controlled cargo release upon exposure to conditions that simulate the intestinal environment. None of the individual CFE or encapsulation components induced inflammation in mouse GI tracts when administered via oral gavage. We also observed a delayed release of fluorescent bead cargo from Alg/Cht microcapsules in mouse intestines following oral gavage. Together, our data suggest that CFE lysate-loaded Alg/Cht formulations can be flexibly used to produce proteins and safely deliver them to the GI tract for potential therapeutic applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=40 SRC="FIGDIR/small/730178v1_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@d3e4c3org.highwire.dtl.DTLVardef@14fbea1org.highwire.dtl.DTLVardef@6c68cforg.highwire.dtl.DTLVardef@15508ec_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG HighlightsO_LICell-free gene expression lysates are active in chitosan coated alginate (Alg/Cht) microcapsules. C_LIO_LIAlg/Cht microcapsules exhibit controlled release in vitro in simulated intestinal-like conditions. C_LIO_LICell-free and encapsulation components do not induce inflammation in the gastrointestinal tracts of male or female mice. C_LIO_LIAlg/Cht microcapsules show controlled delayed cargo release in vivo when orally gavaged in mice. C_LI

Tissue regeneration using bioactive biomaterials has made great progress in the field of wound healing. Biopolymers play a cardinal role in regenerative medicine by providing safe, biocompatible and bioresorbable support. The electrospinning fabrication technique has been used in creating suitable wound care materials. PHBV and PLLA are FDA approved polymers having important applications in biomedical field. In this study, to increase the wound healing potential, PHBV was functionalized with -COOH group and electrospun nano-fibrous mat was produced using PHBV-COOH and PLLA blended solution. Antibiofilm peptide (IDR-1018) with immunomodulatory activity was incorporated into the blended solution to improve infected wound treatment by actively fighting against bacterial infections. Furthermore, in-vitro experiments including cell cytotoxicity assay and scratch wound healing assay were done to evaluate the potential of the synthesized bioactive nanofibrous mat as a potential wound management aid.

Vodobatinib (VBN) is a weakly basic (pKa {approx} 2.3), anticancer treatment with poor enteric solubility and low oral bioavailability. This study demonstrates how an emerging polymeric amorphization technique, slurry conversion, can yield amorphous drug-polymer salts with enhanced dissolution rates. The technique had not previously been applied to a weakly basic drug, so design rules for this class of active were unknown. Two acidic polymers, poly(styrene sulfonic acid) (PSSA) and poly(acrylic acid) (PAA), were individually evaluated for salt formation with VBN. Formulation involved blending the drug and polymer in a 1:2 (v/v) ratio of a protic liquid to solvent and a 1:9 (w/w) ratio of solid to solvent. Design rules for effective combinations of solvents and protic liquids were developed and optimized to thread the needle between dissolution of all species and acid-base interactions, both of which were required to form amorphous salts. Drug loadings of 10%, 20%, and 40% by mass were tested. X-ray photoelectron spectroscopy was employed to evaluate protonation of the quinoline nitrogen atoms on VBN, a key indicator of successful salt formation. Powder X-ray diffraction was used to confirm that the resulting slurry contained amorphous VBN, and 1H NMR spectroscopy indicated residual solvent remained after drying, which remains an area for improvement. In dissolution kinetics tests in FeSSIF, the lead drug-polymer salt formulation achieved a concentration of dissolved VBN up to 140 {micro}g/mL, an improvement of >35-fold compared to <4 {micro}g/mL (LLD) for crystalline VBN. These results demonstrate that slurry conversion is a viable polymeric amorphization technique even for weakly basic drugs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/734800v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1812ceforg.highwire.dtl.DTLVardef@1ad06dcorg.highwire.dtl.DTLVardef@9d8bb7org.highwire.dtl.DTLVardef@13fcbe8_HPS_FORMAT_FIGEXP M_FIG C_FIG

Hydrogels are widely used in sensing, delivery, and tissue engineering because their transport properties can be tuned through material design. However, while hydrogel permeability is often characterized using small molecules, many practical applications depend on the uptake and retention of much larger species, including protein conjugates and nanoparticles. Here, we systematically investigate how polyethylene glycol (PEG)-acrylate hydrogel microparticle formulation influences accumulation of signal-generating probes spanning a broad size range. We fabricated particles across a 36-condition design space varying nominal PEG-acrylate molecular weight, polymer weight percent, and UV crosslinking dose, and related formulation-dependent probe accumulation to particle swelling behavior. Increasing nominal PEG-acrylate molecular weight and decreasing polymer weight percent produced more highly swollen particles and strongly enhanced accumulation of fluorescent streptavidin conjugates, with the largest effects observed for bulky labels such as allophycocyanin and phycoerythrin. Gold nanoparticle accumulation was even more formulation-restricted, with detectable colorimetric signal observed primarily in the most permissive formulations. These findings establish design rules linking PEG hydrogel formulation to size-dependent accumulation and show that formulations suitable for small probes may be inadequate for larger reporters. More broadly, this framework may inform the design of hydrogels for particle-based assays as well as other applications where transport of macromolecules or nanoscale materials is important.