Advanced Healthcare Materials最新文献

Effective treatment of bone diseases is quite tricky due to the unique nature of bone tissue and the complexity of the bone repair process. In combination with biological materials, cells and biological factors can provide a highly effective and safe treatment strategy for bone repair and regeneration, especially based on these multifunctional hydrogel interface materials. However, itis still a challenge to formulate hydrogel materials with fascinating properties (e.g., biological activity, controllable biodegradability, mechanical strength, excellent cell/tissue adhesion, and controllable release properties) for their clinical applications in complex bone repair processes. In this review, we will highlight recent advances in developing functional interface hydrogels. We then discuss the barriers to  producing of functional hydrogel materials without sacrificing their inherent properties, and potential applications in cartilage and bone repair are discussed. Multifunctional hydrogel interface materials can serve as a fundamental building block for bone tissue engineering.

Sonodynamic therapy (SDT), which is non-invasive and controllable has the potential to treat triple-negative breast cancer (TNBC). However, the hypoxia and immunosuppressive tumor microenvironment (TME) often block the production of reactive oxygen species and the induction of SDT-activated immunogenic cell death, thus limiting the activation of adaptive immune responses. To alleviate these challenges, we proposed the development of a multifunctional biomimetic nanoplatform (mTSeIR), which was designed with diselenide-conjugated sonosensitizers and tirapazamine (TPZ), encapsulated within M1 macrophage membrane. This nanoplatform utilized hypoxia-induced chemotherapy to improve the efficacy of SDT, to further enhance adaptive immunotherapy by activating innate immunity and remodeling the immunosuppressive TME. Firstly, the prodrug TPZ was activated due to the increased oxygen consumption associated with SDT. Subsequently, the mTSeIR enhanced repolarization of M2 macrophages to the M1 phenotype. The diselenide component in mTSeIR effectively activated the natural killer cell-mediated antitumor innate immune response. Ultimately, in vivo studies indicated that mTSeIR+US with good biosafety achieved over 98% tumor inhibition and enhanced adaptive immunotherapy. This research presents an efficient approach that addressed the limitations of SDT and achieves simultaneous activation of both innate and adaptive immunotherapy, resulting in significant antitumor and anti-metastatic efficacy in TNBC.

Ultra-broadband photodetectors (UB-PDs) are essential in medical applications, public safety monitoring, and various other fields. However, developing UB-PDs covering multiple bands from ultraviolet to medium infrared remains a challenge due to material limitations. Here, a mixed-dimensional heterojunction composed of 2D WS₂/monodisperse hexagonal stacking (MHS) 3D PdTe₂ particles on 3D Si is proposed, capable of detecting light from 365 to 9600 nm. The exceptional performance of this photodetector is attributed to MHS PdTe₂ particles, which increase the specific surface area and enhance UV-to-NIR absorption of the 2D WS₂ nanofilm. At 980 nm (0 V), the device achieves a responsivity of 7.8 × 10² mA W^-1, a detectivity of 2.5 × 10¹³ Jones, and a sensitivity of 2.6 × 10⁸ cm² W^-1. The MHS PdTe₂ layer amplifies the built-in electric field and enhances heterojunction self-powered capability. This photodetector exhibits a high switching ratio (10⁴), a rapid response time (24.14 µs), and a significant photocurrent gain at zero bias. Its application in blood oxygen saturation analysis is demonstrated based on dual-wavelength photoplethysmography (PPG) at 650 and 905 nm, and infrared perspective imaging at 808 nm. Additionally, the device can differentiate materials based on their transmittance at 9600 nm. This research opens new avenues for the multifunctional use of UB-PDs.

Despite the significant potential of short hairpin RNA (shRNA)-mediated gene therapy for various diseases, the clinical success of cancer treatment remains poor, partly because of low selectivity and low efficiency. In this study, an mRNA-initiated autonomous multi-shRNA nanofactory (RNF@CM) is designed for in vivo amplification imaging and precise cancer treatment. The RNF@CM consists of a gold nanoparticle core, an interlayer of two types of three-stranded DNA/RNA hybrid probes, one of which is bound to aptamer-inhibited DNA polymerases, and an outer layer of the cancer cell membrane. After the specific delivery of RNF@CM into target cancer cells, an intracellular tumour-related mRNA target can initiate the RNF@CM with a circular strand-displacement polymerisation reaction, resulting in the release of significantly amplified fluorescence and continuous production of three types of shRNAs. The RNF@CM effectively distinguished cancer cells from normal cells, exclusively produced multiple shRNAs in response to a specific mRNA target in cancer cells, accurately diagnosed tumours in vivo, and significantly inhibited tumour growth with negligible toxicity, expanding the toolbox for on-demand gene delivery and precision theranostics.

Modern radiotherapy frequently employs radiosensitizers for radiation dose deposition and triggers an immunomodulatory effect to enhance tumor destruction. However, developing glioma-targeted sensitizers remains challenging due to the blood-brain barrier (BBB) and multicomponent instability. This study aims to green-synthesize transferrin-bismuth nanoparticles (TBNPs) as biosafe radiosensitizers to enhance X-ray absorption by tumors and stimulate the immune response for glioma therapy. The proposed protein-based strategy provides TBNPs with BBB-crossing ability and prevents off-target toxicity. Cellular experiments following 4 Gy of X-ray irradiation reveal that TBNPs increase DNA damage in glioma cells and trigger immunomodulation, thereby inducing immunogenic cell death. Furthermore, TBNPs effectively inhibit tumor growth through synergistic radiotherapy and immunotherapy in an orthotopic glioma mouse model. The findings highlight TBNPs as promising radiosensitizers for effective and biosafe radiotherapy with immunomodulation.

Natural plant-derived polysaccharides exhibit substantial potential for treating ulcerative colitis (UC) owing to their anti-inflammatory and antioxidant properties and favorable safety profiles. However, their practical application faces several challenges, including structural instability in gastric acid, imprecise targeting of inflamed regions, and limited intestinal retention times. To address these limitations, pH-responsive, colon-targeting microspheres (pWGPAC MSs) are developed for delivering phosphorylated wild ginseng polysaccharides (pWGP) to alleviate UC. These pWGPAC MSs are fabricated by incorporating pWGP into calcium-crosslinked alginate microspheres with subsequent chitosan surface modification to enhance mucosal adhesion. These pWGPAC MSs demonstrated exceptional stability under acidic conditions while enabling targeted release in the colon. In a mouse model of UC, the pWGPAC MSs effectively mitigated mucosal injury, attenuated inflammation, and restored intestinal barrier function. Further mechanistic investigations revealed that these pWGPAC MSs modulated the TLR4/MYD88 signaling pathway and promoted M2 macrophage polarization. Integrated microbiome and metabolome analyses demonstrated that these pWGPAC MSs regulated the gut microbiota composition and decreased pro-inflammatory metabolite levels. In addition, these microspheres demonstrated promising safety profiles. Collectively, these findings establish pWGPAC MSs as a promising therapeutic strategy for the treatment of UC and provide a solid foundation for future clinical applications.

Poor diabetic wound healing poses a critical threat to human health. Excessive oxidative stress and increased susceptibility to bacterial infection are key issues that impede diabetic wound healing. Cerium oxide nanoparticles (CeO₂ NPs) have attracted increasing attention because of their unique antioxidant and antimicrobial properties. Here, this work designs a near-infrared (NIR) light-responsive gelatin methacryloyl (GelMA)/CeO₂/polydopamine (PDA) hydrogel with antibacterial and antioxidant effects. The hydrogel exhibits a stable, efficient, and controllable photothermal conversion capacity under NIR stimulation. The hydrogel can be used to construct a local microenvironment conducive to chronic diabetic wound healing. Significant antibacterial effects of the NIR-responsive GelMA/CeO₂/PDA hydrogel on both Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) are demonstrated by counting colony-forming units (CFUs) and in bacterial live/dead staining experiments. The strong antioxidant activity of hydrogels is demonstrated by measuring the level of reactive oxygen species (ROS). The effect of the NIR-responsive GelMA/CeO₂/PDA hydrogel in terms of promoting diabetic wound healing is validated in full-thickness cutaneous wounds of diabetic rat models. Additionally, this work describes the mechanism by which the NIR-responsive GelMA/CeO₂/PDA hydrogel promotes diabetic wound healing; the hydrogel inhibits the interleukin (IL)-17 signaling pathway. This NIR-responsive, multifunctional hydrogel dressing provides a targeted approach to diabetic wound healing.

Photodynamic therapy (PDT) is a powerful strategy for tumor therapy with noninvasiveness and desirable efficacy. However, the phototoxicity of photosensitizer after the post-PDT is the major obstacle limiting the clinic applications. Herein, a nitric oxide (NO)-activatable photosensitizer is reported with turn-on PDT behavior and endoplasmic reticulum (ER) targeting ability for precise tumor therapy. Four o-thiophenediamine derivatives with reaction-tunable donor/acceptor push-pull electronic effect are established, and the systematic structure and property relationship observation reveals the following features: 1) the reactivity against NO can be improved by enhancing the electron density and further facilitated upon photo-irradiation. 2) the reactivity with NO enables the improved intramolecular charge transfer process with the evoking of photosensitizing effect. 3) only o-thiophenediamine derivative with ER enrichment behavior exhibited cancer cell ablation effect compared to photosensitizers localized in lysosome and lipid droplet. Thus, the efficient inhibition of cancer cells both in vitro and in vivo is realized based on the photo-controlled PDT strategy. This work provides more insights into developing promising activatable photosensitizers for advanced therapy based on tumor microenvironment trigger.

Metal-protein hybrid materials represent a novel class of functional materials that exhibit exceptional physicochemical properties and tunable structures, rendering them remarkable applications in diverse fields, including materials engineering, biocatalysis, biosensing, and biomedicine. The design and development of multifunctional and biocompatible metal-protein hybrid materials have been the subject of extensive research and a key aspiration for practical applications in clinical settings. This review provides a comprehensive analysis of the design strategies, intrinsic properties, and biomedical applications of these hybrid materials, with a specific emphasis on their potential in cancer therapy, drug and vaccine delivery, antibacterial treatments, and tissue regeneration. Through rational design, stable metal-protein hybrid materials can be synthesized using straightforward methods, enabling them with therapeutic, delivery, immunomodulatory, and other desired functionalities. Finally, the review outlines the existing limitations and challenges associated with metal-protein hybrid materials and evaluates their potential for clinical translation, providing insights into their practical implementation within biomedical applications.