Advanced Healthcare Materials最新文献

Damage and repair are recurring processes in tissues, with fibroblasts playing key roles by remodeling extracellular matrices (ECM) through protein synthesis, proteolysis, and cell contractility. Dysregulation of fibroblasts can lead to fibrosis and tissue damage, as seen in idiopathic pulmonary fibrosis (IPF). In advanced IPF, tissue damage manifests as honeycombing, or voids in the lungs. This study explores how transforming growth factor-beta (TGF-β), a crucial factor in IPF, induces lung fibroblast spheroids to create voids in reconstituted collagen through proteolysis and cell contractility, a process is termed as hole formation. These voids reduce when proteases are blocked. Spheroids mimic fibroblast foci observed in IPF. Results indicate that cell contractility mediates tissue opening by stretching fractures in the collagen meshwork. Matrix metalloproteinases (MMPs), including MMP1 and MT1-MMP, are essential for hole formation, with invadopodia playing a significant role. Blocking MMPs reduces hole size and promotes wound healing. This study shows how TGF-β induces excessive tissue destruction and how blocking proteolysis can reverse damage, offering insights into IPF pathology and potential therapeutic interventions.

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu²⁺ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu²⁺ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H₂O₂ supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu²⁺ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

Microthrombus is one of the major causes of the sequelae of COVID-19 and leads to subsequent embolism and necrosis. Due to their small size and irregular movements, the early detection and efficient removal of microthrombi in vivo remain a great challenge. In this work, an interventional method is developed to identify and remove the traveling microthrombi using targeted-magnetic-microbubbles (TMMBs) and an interventional magnetic catheter. The thrombus-targeted drugs are coated on the TMMBs and magnetic nanoparticles are shelled inside, which allow not only targeted adhesion onto the traveling microthrombi, but also the effective capture by the magnetic catheter in the vessel. In the proof-of-concept experiments in the rat models, the concentration of microthrombus is reduced by more than 60% in 3 minutes, without damaging the organs. It is a promising method for treating microthrombus issues. This article is protected by copyright. All rights reserved.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and represent a pressing clinical need. Vascular occlusions are the predominant cause of CVD and necessitate surgical interventions such as bypass graft surgery to replace the damaged or obstructed blood vessel with a synthetic conduit. Synthetic small-diameter vascular grafts (sSDVGs) are desired to bypass blood vessels with an inner diameter < 6 millimeters yet have limited use due to unacceptable patency rates. The incorporation of biophysical cues such as topography onto the sSDVG biointerface can be used to mimic the cellular microenvironment and improve outcomes. In this review, the utility of surface topography in sSDVG design is discussed. Firstly, the authors introduce the primary challenges that sSDVGs face and the rationale for utilizing biomimetic topography. The current literature surrounding the effects of topographical cues on vascular cell behavior in vitro is reviewed, providing insight into which features are optimal for application in sSDVGs. The results of studies that have utilized topographically-enhanced sSDVGs in vivo are evaluated. Current challenges and barriers to clinical translation are discussed. Based on the wealth of evidence detailed here, substrate topography offers enormous potential to improve the outcome of sSDVGs and provide therapeutic solutions for CVDs. This article is protected by copyright. All rights reserved.

Making the utmost of the differences and advantages of multiple disciplines, interdisciplinary integration breaks the science boundaries and accelerates the progress in mutual quests. As an organic connection of material science, enzymology, and biomedicine, nanozyme-related research has been further supported by computer technology, which injects in new vitality, and contributes to in-depth understanding, unprecedented insights, and broadened application possibilities. Utilizing computer-aided first-principles method, high-speed and high-throughput mathematic, physic, and chemic models are introduced to perform atomic-level kinetic analysis for nanocatalytic reaction process, and theoretically illustrate the underlying nanozymetic mechanism and tructure-function relationship. On this basis, nanozymes with desirable properties can be designed and demand-oriented synthesized without repeated trial-and-error experiments. Besides that, computational analysis and device also play an indispensable role in nanozyme-based detecting methods to realize automatic readouts with improved accuracy and reproducibility. Here, we focus on the crossing of nanocatalysis research and computational technology, to inspire the research in computer-aided analysis in nanozyme field to a greater extent. This article is protected by copyright. All rights reserved.

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membranes and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, the authors delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Last, the challenges and trends in this field are discussed. This comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines.

Wound infections pose a significant challenge in healthcare, and traditional antibiotic treatments often result in the development of resistant pathogens. Addressing this gap, we introduced ProGel, a living hydrogel created by entrapping probiotic Lactobacillus plantarum as a therapeutic component within a gelatin matrix. With a double-syringe system, ProGel can be easily mixed and applied, conforming swiftly to any wound shape and forming hydrogel in situ. It also demonstrated robust mechanical and self-healing properties owing to the Schiff-base bonds. ProGel sustained more than 80% viability of the entrapped L. plantarum while restricting their escape from the hydrogel. After a week of storage, more than 70% viability of the entrapped L. plantarum was preserved. Importantly, ProGel exhibited broad-spectrum antimicrobial efficacy against pathogens commonly associated with wound infections, i.e., Pseudomonas aeruginosa (7Log reduction), Staphylococcus aureus (3-7Log reduction), and Candida albicans (40-70% reduction). Moreover, its cytocompatibility was affirmed through co-culture with human dermal fibroblasts. The effectiveness of ProGel was further highlighted in more clinically relevant tests on human skin wound models infected with P. aeruginosa and S. aureus, where it successfully prevented the biofilm formation of these pathogens. This study showcases an injectable living hydrogel system for the management of complex wound infections. This article is protected by copyright. All rights reserved.

The incorporation of well-designed antibiotic nanocarriers, along with an antibiotic adjuvant effect, in combination with various antibiotics, offers an opportunity to combat drug-resistant strains. However, precise control over morphology and encapsulated payload release can significantly impact their antibacterial efficacy and synergistic effects when used alongside antibiotics. Here, this study focuses on developing lipopeptide-based nanoantibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH-induced collapse and negative-charged-surface-induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug-resistant strains. The modulation regulations of the lipopeptide nanocarriers with modular design are governed by the authors. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip results in a significantly low fractional inhibitory concentration index of 0.375 and a remarkable reduction in the minimum inhibitory concentration of Cip against multidrug-resistant (MDR) Escherichia coli (clinical isolated strains) by up to 32-fold. The survival rate of MDR E. coli peritonitis treated with nanoantibiotics is significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic shows no obvious toxicity to major organs.