Advanced Healthcare Materials最新文献

Characterized by a cascade of profound changes in nucleus pulposus (NP) cells, extracellular matrix (ECM), and biomechanics, intervertebral disc degeneration is a common multifactorial condition that may lead to various degenerative lumbar disorders. Therapeutic strategies targeting a single factor have shown limited efficacy in treating disc degeneration, and approaches that address multiple pathological ingredients are barely reported. In this study, engineered cell membrane-encapsulated keratin nanoparticles are developed to simultaneously alleviate NP cell senescence and promote ECM remodeling. To achieve this, salivary acid glycoengineered adipose mesenchymal stem cell membranes are used to coat keratin, a core protein for structural support and cellular protection. The synthesized cell membrane-coated keratin nanoparticles (MKNs) effectively protected mitochondrial integrity in NP cells from oxidative stress-induced damage. Moreover, MKNs modulate mitochondrial metabolism and attenuate NP cell senescence. In addition, MKNs activate integrins at the cell membrane and enhance the interactions between NP cells and ECM, resulting in increased ECM anabolism and decreased catabolism. The proposed multi-targeted strategy to block the degenerative cycle inside the disc is efficacious for treating disc degeneration and may have the potential for clinical application.

Fluoropolymer alone, as an alternative to lead-based piezoelectric materials, has shown multiple challenges to develop useful sensors for solving real-world problems such as photoacoustic, ultrasound pulse echo, and other non-destructive testing. This work demonstrates the fabrication of high frequency and wide bandwidth transducers with fluoropolymer and highly polarizing cubic single crystal Barium titanate (BaTiO₃) ceramic composite for high resolution in-vivo photo-acoustic and ultrasound imaging. For transducer fabrication, a customized bio-compatible nanocomposite sensor film of PVDF-TrFE (Polyvinylidene fluoride trifluoroethylene)/BaTiO₃ (BTO) is synthesized by drop and dry in heating-cum-electro-poling system for advancing polarization, crystallinity, and higher charge generation. The ratio of nanofiller cubic single crystal BTO and PVDF-TrFE is optimized using characterization techniques such as FTIR, XRD and electrometer. Thereafter, SEM and TGA analyses are performed to study the surface morphology and thermal stability of the sensing film. Transducers with central frequencies varying from 17 to 42MHz are fabricated and tested for both pulse-echo mode and receiving photoacoustic signals. These transducers are used for sensing photoacoustic signals generated from hemoglobin and eumelanin and further for ultrasound and photoacoustic imaging. The imaging results are compared with the results obtained using a commercial ultrasound and photoacoustic imaging device. To the best of the knowledge and available literature, for the first time, the fabrication of ultrasound/photoacoustic transducers with cubic single-crystal nanofiller and fluoropolymer nanocomposite is showed. The detailed transducer fabrication method, characterization results, and imaging of biological tissue using photoacoustic and ultrasound are presented.

The stacking mode in aggregate state results from a delicate balance of supramolecular interactions, which closely affects the optoelectronic properties of organic π-conjugated systems. Then, managing these interactions is crucial for advancing phototheranostics, yet remains challenging. A subtle strategy involving peripheral phenyl groups is debuted herein to transform X-aggregated SQ-H into J-aggregated SQ-Ph, reorienting intermolecular dipole interactions while rationally modulating π-π interactions. Co-assembled with liposomes (DSPE-PEG2000), SQ-Ph nanoparticles (NPs) exhibit low toxicity, superior biocompatibility, and a bathochromic shift to the 1064 nm match-excited NIR-II region, with a fluorescence brightness (ε_1064 nm Φ_NIR-II) of 4129 M^-1 cm^-1 and a photothermal conversion efficiency (PCE) of 48.3%. Preliminary in vivo experiments demonstrate that SQ-Ph NPs achieve a signal-to-background ratio (SBR) of up to 14.29 in NIR-II fluorescence imaging (FLI), enabling highly efficient photothermal therapy (PTT) of tumors guided by combined photoacoustic imaging (PAI). This study not only enriches the J-aggregation library but also provides a paradigm for optimizing photosensitizers at the supramolecular level.

Drug-induced liver injury (DILI) is a common clinical problem with urgent respect to demanding early diagnosis. Exosomal miRNAs are reliable and noninvasive biomarkers for the early diagnosis of DILI. However, accurate and feasible detection of exosomal miRNAs is often hampered by the low abundance of miRNAs, inefficient exosome separation techniques, and the requirement for RNA extraction from large sample volumes. Here, the multifunctional magnetic vesicles are constructed by loading a multiple signal amplification detection system and magnetic nanoparticles into virus-mimicking engineered vesicles to achieve in situ analysis of hepatogenic exosomal miRNAs, which do not require miRNA extraction or target amplification. Virus-mimicking engineered vesicles carrying large surface proteins of hepatitis B virus are designed to achieve the specific identity and fusion of hepatogenic exosomes, and the multiple signal amplification detection system assembled by catalytic hairpin assembly technology and CRISPR/Cas13a technology can achieve highly sensitive in situ detection of miRNAs in exosomes with a low limit of detection (LOD) of 1.25 × 10² particles·µL^-1. This novel nanoplatforms open a promising avenue for the early clinical diagnosis of DILI.

Reproducing the microstructure of the natural cornea remains a significant challenge in achieving the mechanical and biological functionality of artificial corneas. Therefore, the development of cascade structures that mimic the natural extracellular matrix (ECM), achieving both macro-stability and micro-structure, is of critical importance. This study proposes a novel, efficient, and general photo-functionalization strategy for modifying natural biomaterials. Collagen microfibers obtained through electrospinning are functionalized with an active N-Hydroxysuccinimide (NHS) ester, to impart light-curing ability. This approach expands the construction of photo-controllable hydrogel systems beyond conventional single methacrylate (MA) modifications or di-tyrosine bonding, enabling integration with other biomaterials for comprehensive ECM remodeling. Subsequently, the collagen microfibers are then photo-embedded into gelatin methacryloyl (GelMA) via covalent crosslinking to form a fibrous hydrogel, which supports both structural and functional requirements. In terms of biological functionality, the hydrogel promotes significant inward migration and retention of human corneal fibroblasts (hCFs), replicating ECM-like environments. Furthermore, its excellent burst resistance suggests potential as a bioadhesive. In a rabbit model, the hydrogel achieved effective repair of large-sized (6 mm) corneal defects, facilitates epithelial migration, and maintained long-term stability. This work provides valuable guidance for designing efficient and simplified bioactive materials for corneal repair and broader tissue engineering applications.

Noise-induced hearing loss (NIHL) results from prolonged exposure to intense noise, causing damage to sensory outer hair cells (OHCs) and spiral ganglion neurons (SGNs). The blood labyrinth barrier (BLB) hinders systemic drug delivery to the inner ear. This study applied a retro-auricular round window membrane (RWM) method to bypass the BLB, enabling the transport of macromolecular proteins into the inner ear. Pigment epithelium-derived factor (PEDF), which has anti-inflammatory and neuroprotective properties, is conjugated to a prestin-targeting peptide 2 (PrTP2) using N-succinimidyl-3-maleimidopropionate (SMP) to form PrTP2-SMP/PEDF. This compound specifically targeted Prestin and accumulated around OHCs for sustained release, effectively reducing OHC and SGN loss. Functional and structural tests, including auditory brainstem response (ABR), confocal microscopy, and scanning electron microscopy (SEM), revealed significant hearing restoration and cellular protection. Additionally, the results of enzyme-linked immunosorbent assay (ELISA), Annexin V and propidium iodide (PI) staining and immunoblotting show that noise exposure may induce pyroptosis in the cochlea by activating the NOD-like receptor protein 3 (NLRP3)-apoptosis-associated speck-like protein containing a CARD (ASC) - cysteinyl aspartate specific proteinase (Caspase-1) pathway and PrTP2-SMP/PEDF alleviates the inflammatory response by inhibiting pyroptosis. Toxicity analysis indicates no adverse effects, suggesting that PrTP2-SMP/PEDF has a promising therapeutic prospective for NIHL.

Nitric oxide (NO) is an essential molecule in biomedicine, recognized for its antibacterial properties, neuronal modulation, and use in inhalation therapies. The effectiveness of NO-based treatments relies on precise control of NO concentrations tailored to specific therapeutic needs. Electrochemical generation of NO (E-NOgen) via nitrite (NO₂ ^-) reduction offers a scalable and efficient route for controlled NO production, while also addressing environmental concerns by reducing NO₂ ^- pollution and maintaining nitrogen cycle balance. Recent developments in catalysts and E-NOgen devices have propelled NO₂ ^- conversion, enabling on-demand NO production. This review provides an overview of NO₂ ^- reduction pathways, with a focus on cutting-edge Fe/Cu-based E-NOgen catalysts, and explores the development of E-NOgen devices for biomedical use. Challenges and future directions for advancing E-NOgen technologies are also discussed.

Coronary microvascular dysfunction (CMD) refers to clinical symptoms caused by structural and functional damage to coronary microcirculation. The timely and precise diagnosis of CMD-related myocardial ischemia is essential for improving patient prognosis. This study describes a method for the multimodal (fluorescence, ultrasonic, and photoacoustic) noninvasive imaging and treatment of CMD based on ischemic myocardium-targeting peptide (IMTP)-guided nanobubbles functionalized with indocyanine green (IMTP/ICG NBs) and characterizes their basic characteristics and in vitro imaging and targeting abilities. The IMTP/ICG NBs enable the accurate location of myocardial ischemia via photoacoustic imaging, and when loaded with tannic acid (TA), can be used to effectively treat myocardial ischemia and fibrosis in CMD mice, achieving an effect superior to that of free TA. The origin of this high therapeutic efficiency is revealed by transcriptomic and proteomic analyses. This investigation lays the groundwork for visual monitoring and the drug-targeted treatment of CMD.

The porous structure is crucial in bone tissue engineering for promoting osseointegration. Among various structures, triply periodic minimal surfaces (TPMS) -Gyroid has been extensively studied due to its superior mechanical and biological properties. However, previous studies have given limited attention to the impact of unit cell size on the biological performance of scaffolds. In this research, four TPMS-Gyroid titanium scaffolds with different unit cell sizes (TG15, TG20, TG25, and TG30) are fabricated using Selective Laser Melting (SLM) to explore their effects on osseointegration. Mechanical tests revealed that TG15 and TG20 exhibited superior compressive strength. In vitro experiments demonstrated that TG20 facilitated better cell adhesion through robust integrin protein expression initially, which subsequently enhanced cell proliferation and osteogenic differentiation. Furthermore, macrophages on TG20 showed higher Integrin β1 (ITGB1) expression, promoting their polarization to the M2 phenotype, which suppressed inflammation, fostered bone integration, and angiogenesis. In vivo studies confirmed TG20's effectiveness in promoting bone ingrowth by reducing inflammation. This study highlights TG20's structural advantages, making it a promising bone scaffold with exceptional osteogenic and angiogenic properties through osteoimmune microenvironment modulation. Therefore, TG20 holds significant potential for applications in bone tissue engineering.

Spinal cord injury (SCI) leads to acute tissue damage that disrupts the microenvironmental homeostasis of the spinal cord, inhibiting cell survival and function, and thereby undermining treatment efficacy. Traditional stem cell therapies have limited success in SCI, due to the difficulties in maintaining cell survival and inducing sustained differentiation into neural lineages. A new solution may arise from controlling the fate of stem cells by creating an appropriate mechanical microenvironment. In this study, mechanical response stem cell complex (MRSCC) is created as an innovative therapeutic strategy for SCI, utilizing 3D bioprinting technology and gelatin microcarriers (GM) loaded with mesenchymal stem cells (MSCs). GM creates an optimal microenvironment for MSCs growth and paracrine activity. Meanwhile, 3D bioprinting allows accurate control of spatial pore architecture and mechanical characteristics of the cell construct to encourage neuroregeneration. The mechanical microenvironment created by MRSCC is found to activate the Piezo1 channel and prevent excessive nuclear translocation of YAP, thereby increasing neural-related gene expression in MSCs. Transplanting MRSCC in rats with spinal cord injuries boosts sensory and motor recovery, reduces inflammation, and stimulates the regeneration of neurons and glial cells. The MRSCC offers a new tissue engineering solution that can promote spinal cord repair.