Advanced Healthcare Materials最新文献

The significance of biomedical applications of Ti alloys is best emphasized by their widespread utilization as implantable materials, such as internal supports and bone replacements. Ti alloys are sensitive to fretting wear, which leads to the early failure of Ti implants. Improved wear resistance of such implants is essential to ensure a prolonged implant life. Based on the structure-function-integrated concept, this work unprecedentedly designs and fabricates an antibacterial 8SiC/Ti-3Cu composite with improved wear resistance using microwave sintering from pure Ti, Cu, and nano-SiC powders. For comparison, SiC-free Ti-3Cu composite is manufactured under the same conditions using microwave sintering. The addition of 8 vol.% SiC to Ti-3Cu significantly reduces the porosity and pore size of composites. The 8SiC/Ti-3Cu shows a Vickers hardness of 353 HV, compressive strength of 803 MPa, elastic modulus of 28.7 GPa, and a significantly increased wear resistance (wear rate decreased by 70% compared to Ti-3Cu). In addition, 8SiC/Ti-3Cu exhibits excellent electrochemical corrosion resistance, biocompatibility in relation to MC3T3-E1 cells, and a bacteriostatic rate over 99% against E. coli. The combination of the wear-resistant nano-reinforced SiC and antibacterial Ti₂Cu in the 8SiC/Ti-3Cu composite renders it a highly promising implant material.

Poor tumor penetration is the major predicament of nanomedicines that limits their anticancer efficacy. The dense extracellular matrix (ECM) in the tumor is one of the major barriers against the deep penetration of nanomedicines. In this work, a slimming/excavating strategy is proposed for enhanced intratumoral penetration based on an acid-disassemblable nanomicelles-assembled nanomedicine and the NO-mediated degradation of ECM. The nanomedicine is constructed by cross-linking nanomicelles, which are self-assembled with two kinds of dendrimers containing phenylboronic acid and lactobionic acid, through borate esterification. In the acidic tumor microenvironment, the pH-sensitive borate ester bonds among the nanomicelles are hydrolyzed, triggering the disassembly of nanomedicine (≈150 nm) into small nanomicelles (≈25 nm). In response to the intratumoral over-expressed glutathione (GSH), the NO donor loaded in the nanomicelles produces NO, which mediates the expression of matrix metalloproteinases for the degradation of ECM in the tumor. By collaboration of the disassembling behavior of nanomedicine with the NO-mediated degradation of ECM, the designed nanomedicine can penetrate a long distance in tumors. The proposed slimming/excavating strategy will provide inspiration for overcoming the challenge of nanomedicines in tumor penetration.

The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood-brain barrier (BBB) and non-specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP-M-M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP-M-M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF-1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma-associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re-educate immunosuppressive TME, and inhibit the progression of GBM.

Prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. As a countermeasure, a 3D printable robust hydrogel-based tissue-repair platform is developed containing decellularized extracellular matrix (dECM) from differentiated mammalian cells as the therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells are differentiated in vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. Integrating the bioactive dECM from differentiated cell sources allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hASCs) toward osteogenic and chondrogenic lineages. Further, GelO and GelC can be covalently adhered using a carbodiimide coupling reaction, forming a multi-layered hydrogel with potential application as a bioactive osteochondral plug. The designed multi-layered hydrogel can also induce differentiation of hASCs in vitro. In conclusion, the bioactive dECM carrying 3D printed robust hydrogel offers a promising new drug and cell-free therapeutic strategy for bone and cartilage repair and future osteoarthritis management.

Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains. Anti-cancer drugs are tethered to the backbone via a clinically approved valine-citrulline (VC) linker. This design leverages the tumor's reductive environment and Cathepsin B overexpression for BBP rapid degradation and precise drug release restricted within tumor cells, thereby addressing systemic safety concerns over synthetic BBP and expanding the therapeutic window of anti-cancer drugs simultaneously. Surface fluorination of BBP further enhances tumor accumulation and deep penetration. In vivo studies with monomethyl auristatin E (MMAE)-loaded BBP in tumor-bearing mice demonstrate substantial tumor suppression with minimal side effects. Together, these findings highlight the potential of responsive degradable BBP as a versatile unimolecular platform for cancer drug delivery, addressing existing challenges associated with synthetic BBP nanomedicines.

Urinary catheters serve as critical medical devices in clinical practice. However, the currently used urinary catheters lack efficient antibacterial and lubricating properties, often leading to discomfort with patients and even severe urinary infections. Herein, a new strategy of supramolecular assembly and disassembly of chitosan (Cs) is developed that enables efficient antibacterial lubricous and biodegradable hydrogel urinary catheters. Sodium lauryl sulfonate (SLS) is employed to induce supramolecular assembly on the surface of Cs film strips in an aqueous solution, resulting in the formation of hollow hydrogel catheters of Cs@SLS. Subsequent disassembly in a strong alkaline solution eliminates the SLS component, yielding neat Cs hydrogel catheters. The mechanical strength of these catheters reaches 16 MPa, exceeding that of similar devices made of plastics. The Cs hydrogel catheters are endowed with high antibacterial activity, capable of inhibiting the growth of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Proteus mirabilis(P. mirabilis) on its surface, while these bacteria are found to proliferate rapidly on plastic catheters within 24 h. They also demonstrate excellent lubricity, with a friction coefficient approaching zero, and thus about 13 times lower than that of plastic catheters. In vivo tests further confirm the biodegradability of the catheters, highlighting their strong potential for clinical applications.

Microelectrode array (MEA) techniques provide a powerful method for exploration of neural network dynamics. A critical challenge is to interface 3D neural tissues including neural organoids with the flat MEAs surface, as it is essential to place neurons near to the electrodes for recording weak extracellular signals of neurons. To enhance performance of MEAs, most research have focused on improving their surface treatment, while little attention has been given to improve the tissue-MEA interactions from the medium side. Here, a strategy is introduced to augment MEA measurements by overlaying perfluorodecalin (PFD), a biocompatible fluorinated solvent, over neural tissues. Laying PFD over cerebral organoids insulates and compresses the tissues on MEA, which significantly enhances electrophysiological recordings. Even subtle signals such as the propagation of action potentials in bundled axons of motor nerve organoids can be detected with the technique. Moreover, PFD stabilizes tissues in acute recordings and its transparency allows optogenetic manipulations. This research highlights the potential of PFD as a tool for refining electrophysiological measurements of in vitro neuronal cultures. This can open new avenues to leverage precision of neuroscientific investigations and expanding the toolkit for in vitro studies of neural function and connectivity.

Wound care challenges healthcare systems worldwide as traditional dressings often fall short in addressing the diverse and complex nature of wound healing. Given conventional treatments limitations, innovative alternatives are urgent. Additive manufacturing (AM) has emerged as a distinct and transformative approach for developing advanced wound dressings, offering unprecedented functionality and customization. Besides exploring the AM processes state-of-the-art, this review comprehensively examines the application of AM to produce cellular-compatible and bioactive, therapeutic agent delivery, patient-centric, and responsive dressings. This review distinguishes itself from the published literature by covering a variety of wound types and by summarizing important data, including used materials, process/technology, printing parameters, and findings from in vitro, ex vivo, and in vivo studies. The prospects of AM in enhancing wound healing outcomes are also analyzed in a translational and cost-effective manner.

The predominant adverse health effects in care delivery result from hospital-acquired (nosocomial) infections, which impose a substantial financial burden on global healthcare systems. Integrating contact-killing antibacterial action, gas permeability, and antioxidant properties into textile coatings offers a transformative solution, significantly enhancing both medical and everyday protective applications. This study presents an innovative, pollution-free physical compounding method for creating a fluorescent biopolymer composite embedded with silicene-based heteroatom-doped carbon quantum dots for the production of functional textiles. The resulting coated fabric shows superior ultraviolet (UV) protection behavior (UV_A and UV_B), thermal stability, breathability, mechanical strength, and antioxidant capabilities as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) experiment (>78%) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS assay (>90%). Rigorous testing against both gram positive and gram negative bacteria confirms that the coated fabric has excellent antibacterial activity. Results from time-dependent antibacterial assays indicate that the nanocomposite can markedly inhibit bacterial proliferation within a few hours. Molecular dynamics modeling, in conjunction with experimental investigations, is employed to elucidate the intermolecular interactions influencing the components of the treated cotton fabrics. The ongoing research can result in the creation of cost-effective smart textile substrates aimed at inhibiting microbial contamination in healthcare and medical applications, possibly rendering them commercially viable.

Inspired by the emerging potential of photoluminescent hydrogels, this work unlocks new avenues for advanced biosensing, bioimaging, and drug delivery applications. Carbon quantum dots (CDs) are deemed particularly promising among various optical dyes, for enhancing polymeric networks with superior physical and chemical properties. This study presents the synthesis of CDs derived from Prunella vulgaris, a natural plant resource, through a single-step hydrothermal process, followed by their uniform integration into hydrogel matrices via an in situ free radical graft polymerization. The resulting CD-integrated hydrogels exhibit multifunctionality in biomedical applications, featuring a diffusion-controlled drug release mechanism, permit concurrent delivery of photoluminescent CDs and therapeutic agents, enabling real-time monitoring over 32 h. In addition, these hydrogels function as a broad-range optical pH sensor (pH 3-11), provide robust ultraviolet (UV) shielding, and demonstrate nanozyme-like peroxidase activity. Critically, biocompatibility tests confirm their non-cytotoxicity toward fibroblast cells, establishing these hydrogels as promising candidates for diverse biomedical applications. These include advanced wound dressings that monitor the healing process and detect infection through pH sensing, and promote healing through the nanozymatic activity, all while maintaining a moist wound microenvironment. These hydrogels demonstrate exceptional suitability for advanced smart drug delivery, effective UV-blocking, and as innovative platforms for in vivo sensing and bioimaging.