Advanced Healthcare Materials最新文献

Bacterial resistance is gaining ground and novel, unconventional strategies are required to improve antibiotic treatments. As a synthetic analog of planktonic bacilli, the natural bacterial swimmers that can penetrate bacterial biofilms, ultra-short propelling magnetic nanochains are presented as bioinspired magnetic nanorobots, enhancing the antibiotic treatment in biofilm-forming Staphylococcus epidermidis. Propelling nanochains, activated by a low intensity (<20 mT) and low frequency (<10 Hz) rotating magnetic field (RMF), prompt the otherwise resistant biofilm-forming bacteria to become sensitive to methicillin, resulting in the killing of 99.99% of bacteria. While magnetic force-driven spherical magnetic nanoparticles were previously reported as unidirectional biofilm channel diggers, propelling nanochains emerge as second-generation magnetic nanorobots, which, due to their magnetic core, shape anisotropy, and negative zeta potential, combine magnetic responsiveness, torque-driven movement, and attractive electrostatic interactions to attach to bacterial aggregates and multi-directionally protrude throughout the biofilm, indulging mechanical forces. These synergistic effects, in combination with an antibiotic drug, destroy the bacterial extracellular matrix and eradicate the formed biofilm, as confirmed with several complementary techniques.

The regulation of the charged microenvironment around implants is an effective way to promote osseointegration. Although homeostasis of the charged microenvironment plays an integral role in tissues, current research is externally invasive and unsuitable for clinical applications. In this study, functional materials with different surface potential differences are prepared by changing the spatial layout of Ta and Ag on the surface of a Ti-6Al-4V alloy (TC4). This naturally formed an endogenous electric field (EEF) with a negatively charged cell membrane after in vivo implantation and promoted osseointegration at the interface between the bone and implant through the upregulation of Ca²⁺ concentration and activation of subsequent pathways. Interestingly, the promotion of stem cell differentiation, regulation of the direction of immune cell polarization, and antibacterial efficacy are determined by the free charge contained in the implant, rather than by the magnitude of the surface potential difference. This functional implant represents a unique strategy for regulating the charged microenvironment around the implant and enhancing osseointegration, thereby providing ideas and technical approaches for the clinical development of novel implant materials.

Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (K_obs) between PyA-γ-CD and heparin as high as 9.85 × 10⁶ M^-1. The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA-γ-CD not only exhibits nearly complete neutralization activity for unfractionated heparin (UFH), but more importantly, it also effectively neutralizes three LMWHs (dalteparin (Dalte), enoxaparin (Enoxa), and nadroparin (Nadro)) with a broader therapeutic window compared to protamine. The top neutralization activity of PyA-γ-CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA-γ-CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA-γ-CD holds significant potential as a heparin antidote for clinical applications.

Medical catheters are susceptible to biological contamination and pathogen invasion, leading to infection and inflammatory complications. The development of antimicrobial coatings for medical devices has emerged as a promising strategy. However, limited biological functionality and the incompatibility between bactericidal properties and biosafety remain great challenges. Herein, a multifunctional polymer coating (CPB-Ac) is created, incorporating an ultrasonic-responsive carbon monoxide release unit (CORM-Ac) and antifouling unit to treat catheter-related complications. As-synthesized CPB-Ac polymer can be stably anchored to various medical devices with arbitrary shapes and compositions via facile UV treatment. Both in vivo and vitro experiments demonstrated that this multi-functional coating exhibits anti-fouling, anti-inflammatory, and broad-spectrum antibacterial activities as well as good biosafety. During the initial implantation phase, the antifouling units of CPB-Ac coating effectively inhibit the attachment of biological contaminants, significantly reducing the risk of thrombosis and bacterial infection. Once bacterial infection occurs, ultrasonic irradiation can activate CPB-Ac coating to release CO with a much higher amount of 55.3 µm than non-ultrasound controls, therefore rapidly eliminating bacteria and alleviating inflammatory response. It is believed that the work may provide an effective method for the development of next-generation intelligent medical coatings against catheter-related complications.

Coacervates have garnered significant attention as potential drug carriers. However, the instability resulting from their intrinsic membrane-free nature restricts the application of coacervates in drug delivery. Herein, the engineering of poly(ethylene glycol) nanoparticles (PEG NPs) is reported using coacervates composed of PEG and polyphenols as the templates, where PEG is subsequently cross-linked based on different chemistries (e.g., thiol-disulfide exchange, click chemistry, and Schiff base reaction). The reported assembly strategy avoids the template removal process and the resultant PEG NPs exhibit excellent stability in the physiological environment compared to coacervates. The presence of polyphenols in PEG NPs enables the loading of various cargos including metal ions (i.e., Ru, Gd, Mn, Fe) and drug molecules (i.e., doxorubicin), which demonstrates their promise in magnetic resonance imaging and combinational tumor therapy. This work provides a promising strategy to promote the development of coacervate-derived NPs as a drug delivery system for biomedical applications.

Effective glycemic control is paramount for optimal wound healing in diabetic patients. Traditional antibacterial and anti-inflammatory treatments, while important, often fall short in addressing the hyperglycemic conditions of diabetic wounds. Therefore, the development of novel therapeutic strategies for accelerating diabetic wound healing has garnered escalating attention. Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers constructed through strong covalent bonds. Their exceptional structural tunability renders them as an ideal platform for advanced therapeutic applications. Herein, two redox-responsive Zn(II)-coordinated porphyrin COF hydrogels are constructed, which demonstrate rapid blood glucose reduction in localized tissues, along with improved angiogenesis, reactive oxygen species (ROS) scavenging, and photothermal antimicrobial capacities within the hyperglycemic blood environment of diabetic patients, thereby effectively controlling infections and concurrently promoting wound healing. Specifically, COFs with built-in dual active sites, i.e., disulfide or diselenide moieties, can be cleaved by ROS, releasing Zn(II) ions that possess antibacterial and tissue-repairing properties. Furthermore, the Zn(II)-porphyrin COF exhibits glucose oxidase (GOX)-like activity, catalyzing the conversion of glucose into non-glucose metabolites. This synergistic combination of glucose-responsive Zn(II) release and GOX-like activities effectively restores tissue redox balance and improves the wound microenvironment, offering a promising strategy for the diagnosis and treatment of diabetic wounds.

With the advent of multi-layered and 3D scaffolds, the understanding of microbiome composition and pathogenic mechanisms within polymicrobial biofilms is continuously evolving. A fundamental component in mediating the microenvironment and bacterial-host communication within the biofilm are bilayered nanoparticles secreted by bacteria, known as bacterial extracellular vesicles (BEVs), which transport key biomolecules including proteins, nucleic acids, and metabolites. Their characteristics and microbiome profiles are yet to be explored in the context of in vitro salivary polymicrobial biofilm. This pilot study aimed to compare the profiles of BEVs from salivary biofilm cultured on a 2D tissue culture plate and 3D melt electrowritten medical-grade polycaprolactone (MEW mPCL) scaffold. BEVs derived from MEW mPCL biofilm exhibited enhanced purity and yield without altered EV morphology and lipopolysaccharide (LPS) content, with enriched BEVs-associated DNA from Capnocytophaga, porphyromonas, and veillonella genus. Moreover, compared to saliva controls, MEW mPCL BEVs showed comparable DNA expression of Tannerella forsythia, and Treponema denticola and significantly higher expression in Porphyromonas gingivalis, Eikenella corrodens and Lactobacillus acidophilus. Together, these findings highlight a more detailed microbial profile with BEVs derived from salivary biofilms cultured on 3D MEW PCL scaffolds, which facilitates an effective in vitro model with a greater resemblance to naturally occurring biofilms.

Implantation of a mesh loaded with mesenchymal stem cells (MSCs) is a common approach for the treatment of pelvic organ prolapse (POP). The mesh provides effective support to pelvic floor, enhancing muscle contraction of pelvic organs while reducing inflammation. In this study, a fully degradable mesh is designed for the treatment of POP, utilizing MSCs stimulated by a galvanic battery-powered electric field. The bioelectronic mesh consists of two parts: a galvanic cell film and a porous hydrogel loaded with MSCs. The battery film has a flexible substrate, on which Zinc and Molybdenum film electrodes form a galvanic cell that discharges at up to 1.2 V, stimulating cell proliferation and migration of the MSCs pre-loaded in the hydrogel. The hydrogel provides anchoring and growth sites for the MSCs. The bioelectronic mesh elevates the production of elasticity-related and healing-related factors, enhancing the strength and elasticity of the pelvic tissue and promoting tissue regeneration for POP repair. Compared to traditional stem cell therapy, the local stimulation strategy significantly reduces inflammation in pelvic tissues. In addition, the bioelectronic mesh completely degrades after in vivo application, which avoids risks caused by surgical removal, demonstrating good biocompatibility in the implanted mesh.

Lack of timely prognosis of cardiovascular condition (CVC) is resulting in increased mortality across the globe. Currently, available techniques are confined to medical facilities and need the intervention of specialists. Frequently, this impedes timely treatment, driven by socioeconomic factors. Consequently, the disease transcends toward incurable complications. In such a scenario, point-of-care diagnostic tools can help with prognosis at an early stage. Albeit there are such tools available, it is imperative to develop affordably in uncomplicated manufacturing techniques and should have simple readout and analysis modules for monitoring CVC. Accordingly, the solvent-free manufacturing of stencil printable liquid elastomer-carbon nanotube electronic skin-based strain sensor, capable of accurately detecting pulse (at different positions) and other parameters like augmentation index and stiffness index of artery related to the CVC, is reported. The Poincare plot, derived from the recorded data, measures heart rate variability, a key indicator linked to mortality. Thanks to the staggering linearity, gauge factor of 234.26, fast response time of 85 ms (measured from pulse data), and cyclic stability (over 500 cycles), assist in the ease of detection of vital parameters. Furthermore, the sensor patch demonstrates its capability to acquire pulse waves under different real-time artery conditions using cuff-based pressure applications.

Phototheranostics integrates light-based diagnostic techniques with therapeutic interventions, offering a non-invasive, precise, and swift approach for both disease detection and treatment. The efficacy of this approach hinges on the multimodal imaging potential and photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs). Despite the promise, crafting multifunctional phototheranostic organic small molecules brims with challenges. In this research, four innovative xanthene-derived PTAs are synthesized by fine-tuning the donor-π-acceptor (D-π-A) system to strike a balance between radiative and nonradiative decay. The inherent robust photostability and intense fluorescence of the traditional xanthene core are preserved, meanwhile the addition of highly electron-withdrawing groups boosts the non-radiative decay rate to enhance PCE and photoacoustic imaging capabilities. Remarkably, one of the PTAs, DMBA, demonstrates an exceptional absolute fluorescence quantum yield of 2.46% in PBS, and when encapsulated into nanoparticles, it achieves a high PCE of 79.5%. Consequently, DMBA nanoparticles (DMBA-NPs) are effectively employed in fluorescence, 3D photoacoustic, and photothermal imaging-guiding tumor photothermal therapy. This represents the first instance of a multimodal phototheranostic xanthene agent achieving synergistic fluorescence and photoacoustic imaging for diagnostic purposes. Furthermore, this work paves the way for leveraging xanthene fluorophores as versatile tools in the development of multifunctional reagents.