ACS Applied Bio Materials最新文献

Chronic wounds result in extended healing durations and increased susceptibility to infections. Wound infections pose a major obstacle to the healing process. Dressings with improved antibacterial properties should be used to treat chronic, infected wounds. In this work, carboxymethyl cellulose (CMC), poly(vinyl alcohol) (PVA), and polyvinylpyrrolidone (PVP) were used to fabricate a polymeric patch with molybdenum oxide (MoO₃) nanoparticles and naringin. Molybdenum oxide (MoO₃) nanoparticles were synthesized using the wet chemical method and characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). The antibacterial activity of MoO₃ was evaluated using diffusion, colony count, growth curve analysis, and biofilm disruption methods. Biocompatibility, swelling behavior, degradation rate, porosity, drug release profile, water vapor transmission rate (WVTR), and MTT and scratch assays were used to evaluate the fabricated polymer patches (CMC/PVA/PVP with and without MoO₃ and naringin). In an in vivo wound healing study, the CMC/PVA/PVP/MoO₃/naringin patch demonstrated enhanced healing, with 91% wound closure in 15 days in a full-thickness excisional wound model in Wistar rats.

Colon-targeted delivery systems offer a promising approach for local drug administration. In this study, we developed a customized polymeric blend for this purpose, combining polyethylene glycol (PEG), polycaprolactone (PCL), and hydroxypropyl methylcellulose (HPMC). Although PEG and PCL have been extensively studied, the inclusion of HPMC in such blends remains underexplored; however, its use in this context shows significant potential due to its pH sensitivity. To achieve this, various formulations were tested to optimize the thermomechanical and release characteristics of capsules produced through injection molding. Three blends containing 22, 24, and 34 wt% HPMC were processed and analyzed using rheological methods, ATR-FTIR, TGA, DSC, SEM, and in vitro release tests with methylene blue as a model compound. Simulated pH-release tests (pH 2.5, 5, and 6.8) showed minimal release in gastric and intestinal environments, with controlled and sustained release under colonic pH conditions. It was also observed that the initial HPMC content affects the release rate of the model compound. Specifically, when the blend contains 34% HPMC, approximately 38% of the compound is released within 12 h and 73% within 24 h. These results highlight the potential of pH-sensitive polymer blends as effective platforms for colon-targeted drug delivery. A model illustrating how the release rate depends on pH value and HPMC amount was also proposed and validated. The process was considered to happen in two stages: initially, the release medium penetrates the capsule and solubilizes the model compound; then, the model compound is released into the surrounding environment.

Small-diameter vascular grafts (SDVGs, <6 mm) exhibit significant potential as alternatives to coronary and peripheral arteries, yet their clinical application is hindered by thrombosis and intimal hyperplasia. A synergistic modification strategy utilizing polydopamine (PDA) and lysine (Lys) was developed to functionalize polyimide (PI) fibers, aiming to enhance the antithrombotic properties and endothelial regeneration capacity of SDVGs. Alkaline etching activates PI fibers and facilitates the formation of PDA-Lys composite coatings through Schiff base and Michael addition reactions. Characterization results demonstrate that the modified fibers exhibit significantly reduced surface roughness and enhanced hydrophilicity, while retaining high mechanical strength and thermal stability. Hemocompatibility assessments reveal that PI-PDA-Lys fibers exhibit a hemolysis rate below 3.4% and an 80% reduction in platelet adhesion relative to unmodified fibers. This performance improvement is attributed to the optimized surface charge balance and reduced surface roughness. Human umbilical vein endothelial cells (HUVECs) show high viability, sustained proliferation over 7 days, and enhanced migration toward PI-PDA-Lys scaffolds. This multifaceted surface engineering strategy effectively addresses the critical challenges of thrombosis and delayed endothelialization in SDVGs. The modified PI fibers demonstrate significant potential to serve as a viable platform for the development of advanced small-diameter vascular grafts.

Erythrocyte-derived microparticles containing near-infrared (NIR) dyes such as indocyanine green present a promising cell-based platform for optical imaging and phototherapeutics. Using real-time intravital NIR fluorescence imaging of mice vasculature, we investigated the effects of blood type, specifically O⁺ and B⁺, used in fabricating these particles, the number concentration (N_v) of the particles, and the relocalization of phosphatidylserine (PS) to the outer leaflet of the particles' membrane on the resulting circulation dynamics following a single retro-orbital injection. Additionally, we quantified the biodistribution of particles in various organs. We found that the fluorescence emission half-life for particles engineered from O⁺ blood type extended from 11.4 ± 3.0 to 43.1 ± 9.6 min with increased N_v from a low range of 0.4-0.6 to high range of 1.4-1.6 million particles/per μL, when only 30-55% of the particles demonstrated externalized PS. For these particles, the liver and gallbladder, lungs, and spleen showed similar levels of accumulation at 60 min post administration. When >90% of O⁺-particles showed PS externalization, or when the particles were fabricated from B⁺ blood type despite PS externalization in 30-55% of the particles, the emission half-life was reduced to 15.8 ± 5.9 and 18.1 ± 4.6 min, respectively. There was lower accumulation of these particles in the spleen as compared to the liver and gallbladder and the lungs. In vitro experiments demonstrated increased PS externalization correlated to a more efficient uptake of the particles by macrophages. These findings emphasize the importance of blood type, N_v, and PS in engineering erythrocyte-derived particles for future clinical applications.

Wound infection causes excessive inflammation, delays healing, and may lead to severe complications. An ideal dressing should release antibacterial agents on demand to eradicate pathogens locally. Enzyme-responsive drug release systems are highly biocompatible and specific, yet their application in chitosan hydrogels has been limited by imprecise control over release profiles, mechanical properties, and potential drug resistance from premature leakage. Herein, we developed a dual-enzymatically responsive chitosan hydrogel for the on-demand release of antibacterial nanoparticles (ANPs). By synthesizing a series of hydroxyphenyl- and N-acetyl-modified glycol chitosan (HPPA-GC), we tuned the hydrogel stiffness and lysozyme degradation kinetics. Broad-spectrum ANPs were encapsulated via photo-cross-linking. Lysozyme, abundant in infected wounds, triggered hydrogel degradation and ANP release in vitro. When applied to S. aureus-infected full-thickness wounds in mice, the ANP-loaded hydrogel effectively combated infection and accelerated healing. This study demonstrates a robust and biocompatible platform for enzyme-triggered antimicrobial delivery, showing promise for the future development of smart wound dressings.

A dual pH- and redox-responsive macromolecular prodrug of tacrolimus (TAC; FK506) was strategically developed through a stepwise approach involving the conjugation of hyaluronic acid (HA) with cystamine, followed by hydrazide functionalization and final coupling with succinate-modified tacrolimus. The resulting conjugate HA-cystamine-hydrazide-tacrolimus (HA-ss-NHNH₂-TAC or HSNT), confirmed by ¹H NMR, spontaneously formed stable micellar nanostructures as observed under a transmission electron microscope (TEM). The developed micelles possess an average particle size of about 200 nm, as measured by dynamic light scattering (DLS) and exhibited an acceptable polydispersity index, suggesting a relatively uniform and consistent size distribution. The developed system exhibited a high drug loading capacity (10.24%). Cellular uptake studies demonstrated that pretreatment of HCT-116 cells with excess HA to block CD44 receptors significantly reduced intracellular fluorescence, confirming receptor-mediated endocytosis of TAC/HSNT micelles. Further, hemolysis analysis showed less than 5% hemolysis upon incubation with red blood cells, highlighting the nonhemolytic and biocompatible nature of the micelles at the tested concentrations. The dual responsive polymeric micelles have the potential for further translational studies.

The silver nanoparticles were synthesized utilizing the Cordia macleodii (Griff.) Hook.F. & Thamos plant extract. The synthesis of nanoparticles was confirmed through UV-visible spectroscopy, exhibiting a distinct surface plasmon resonance (SPR) absorbance peak at 425 nm. Fourier-transform infrared spectroscopy (FTIR) analysis results revealed the different characteristic peaks corresponding to functional groups responsible for the reduction and stabilization of the silver nanoparticles. The X-ray diffraction (XRD) analysis confirmed a crystalline cubic structure with an average crystalline size of 13.31 nm. Dynamic light scattering (DLS) analysis revealed a hydrodynamic diameter of 114.50 nm with a polydispersity index (PDI) of 22% and a ζ-potential of -10.7 ± 0.8 mV. Field emission electron microscopy (FE-SEM) analysis of nanoparticles displayed a distinct spherical and oval-like shape with uniform morphology, and Engergy dispersive X-ray (EDX) mapping analysis confirmed the presence of Ag (93.39%), C (2.56%), and O (4.05%) by weight percentage. The High-resolution transmission electron microscopy (HR-TEM) exposed the silver nanoparticles as nearly spherical, with some aggregation, and an average diameter of 24.30 ± 11.13 nm. Inhibition in the growth of phytopathogenic bacteria Erwinia carotovora and Ralstonia solanacearum occurred at a 1000 μg/mL concentration of nanoparticles. Nanoparticles were found to accelerate the formation of reactive oxygen species (ROS). The antifungal activity of silver nanoparticles was observed at different concentrations of the nanoparticles. At a 1500 μg/mL concentration of nanoparticles, inhibition of growth was observed: 53.72% for Alternaria alternata, 59.00% for Aspergillus flavus, 53.23% for Botrytis cinerea, and 56.11% for Fusarium oxysporum. The antioxidant activity of silver nanoparticles showed 18.46% free radical scavenging through DPPH assay and 51.99% through ABTS assay at an 80 μg/mL concentration. This study provides an easy, eco-friendly method to fabricate silver nanoparticles for agricultural and other various applications.

Due to its noninvasiveness and high spatiotemporal selectivity, photodynamic therapy has been used clinically to treat superficial tumors for decades. However, the low tissue penetration of external excitation light makes it ineffective against deep-seated tumors and metastases. To fundamentally address this limitation, laser-free self-illuminating photodynamic therapy using internal light sources has emerged as a potential solution. It involves the use of platforms that are driven either through oxidative chemical excitation, such as chemiluminescence and bioluminescence, or radiological excitation from β-emitting isotopes in the form of Cherenkov luminescence. The electronic excitations generated are then transferred to the photosensitizers by different energy transfer mechanisms. This review offers a thorough overview of recent progress in self-illuminating PDT technologies, focusing on key energy transfer mechanisms such as resonance energy transfer, chemically induced electron exchange luminescence, and Cherenkov radiation energy transfer. We have used contemporary examples from the literature and critically analyzed the aspects that make these platforms successful as compared to conventional systems. In the end, we have presented a brief discussion on the current challenges with remedial measures and future perspectives of self-illuminating photodynamic therapy, which will help researchers to design new innovative internal light sources to overcome the major limitation of photodynamic therapy and further expand its application to deep-seated and metastatic tumors.

Management of wounds unveils various crucial clinical constraints, emphasizing the demand for transformed wound dressings that maximize the healing process and facilitate tissue regeneration. Here, a simple, green yet scalable approach was established to fabricate a multifunctional nanocomposite hydrogel employing plant- and animal-derived polymers, specifically almond gum and gelatin, enhanced with bioactive L-menthol and Ae-ZnONPs (MeZ@ALGEL), to improve wound healing by reinforcing the wound environment with its bactericidal, reactive oxygen species (ROS) regulation, and tissue regeneration abilities. MeZ@ALGEL exhibits necessary physicochemical and mechanical properties and significant antibacterial and antioxidant activities, making it ideal for topical administration and beneficial in accelerating wound repair. Under in vitro conditions, MeZ@ALGEL demonstrates a high degree of biocompatibility with fibroblast cells, actively promotes their migration in wound-like cases, and indicates improved hydroxyproline content with upregulation of Col-1, Col-3, Vegf genes, and downregulation of the Il-1b gene revealed in gene expression analysis. In vivo studies using Caenorhabditis elegans as a preliminary wound model reveal that the MeZ@ALGEL hydrogel is nontoxic up to the concentration of 125 μg/mL, promotes healing of glass wool-mediated wounds, exhibits strong antimicrobial activity, and accelerates wound repair through a multifaceted approach involving bacterial eradication, regulation of ROS, and stimulation of collagen synthesis, ultimately enhancing wound healing in the model organism. By these findings, the facilely synthesized nanocomposite hydrogel opens up the possibilities for developing multifunctional hydrogels of natural origin by utilizing the synergistic interaction of components and offers great potential in the wound care sector.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer with the poorest prognosis and lowest survival rate. Therefore, innovative therapeutic strategies, such as nucleic acid medicines, are required. However, vascular-mediated nucleic acid delivery remains a major challenge. In particular, when targeting tumors, it is more difficult to reach deep target cells because of the complex structures within the tumor microenvironment. A combination of physical energy and stimuli-responsive carriers is expected to easily break through barriers in this microenvironment. We have developed ultrasound-responsive nanobubbles (NBs) with lipid shells that serve as gene and nucleic acid delivery tools and ultrasound contrast agents. Furthermore, we reported that NBs containing anionic lipids have high in vivo stability and are useful as carriers of cationic molecules. In this study, we developed a simple and versatile method for loading nucleic acids onto the surfaces of anionic NBs, which are stable in vivo, by coating them with the cationic polysaccharide, methyl glycol chitosan (MGC). Additionally, the utility of the MGC-coated NBs (MGC-NBs) as systemic nucleic acid delivery tools was verified. Furthermore, we attempted to deliver microRNA-145, which serves as a tumor suppressor, to tumor-bearing mouse models of TNBC and evaluated the usefulness of our method for tumor therapy.