Advanced Healthcare Materials最新文献

The inflammatory cascade initiated by acute spinal cord injury (SCI) is a crucial element contributing to subsequent pathological damage. Uncontrolled or excessive inflammatory responses aggravate neural tissue destruction and hinder the regenerative process. Stimulator of interferons genes (STING) is a key regulator in the innate immune signaling pathway that promotes the generation of inflammatory mediators by activating the TBK1 and IRF3 signaling pathways, thereby shaping the post-injury microenvironment. In this study, we developed a hyaluronic acid-phenylboronic acid-polyvinyl alcohol-based hydrogel (HA-PBA-PVA, termed HPP) as a local delivery vehicle for the STING-specific inhibitor C-176, which was applied directly to the injury epicenter in a rat model of complete spinal cord transection. The locally implanted C-176@HPP can effectively deliver C-176 to the injured site, markedly reducing the expression of pro-inflammatory cytokines by regulating the STING/TBK1 signaling pathway. Moreover, the administration of C-176@HPP can significantly attenuate microglial activation and promote neuronal survival and axonal regeneration, which eventually contribute to locomotor improvement after SCI. Our findings demonstrate that C-176@HPP provides a promising strategy for ameliorating neuro-inflammation and facilitating neural tissue regeneration after SCI.

Fibroblast-mediated decreased collagen synthesis is a key aspect of skin aging. Polyhydroxyalkanoate (PHA) materials have established clinical biocompatibility; however, the direct mechanisms of PHA microspheres on fibroblast-mediated skin rejuvenation remain unexplored. We aimed to investigate the impact of PHA microspheres on collagen production and its underlying molecular pathways. The microspheres demonstrated high biocompatibility, promoting human fibroblast proliferation in vitro and showing robust systemic safety in a rat model. In vivo, PHA microsphere injection significantly increased epidermal thickness and the expression of collagen I and III. Mechanistically, PHA microspheres improved mitochondrial function, as evidenced by elevated ATP production. MYBL2 was identified as a key transcriptional regulator; its knockdown attenuated fibroblast proliferation, collagen synthesis, and mitochondrial function. Importantly, PHA stimulation failed to rescue this effect, confirming that MYBL2 is required for the observed regeneration. In summary, we demonstrate that PHA microspheres drive fibroblast proliferation and collagen synthesis by upregulating MYBL2 and enhancing mitochondrial function. These findings provide a theoretical basis for the application of PHA microspheres as a collagen stimulant for skin rejuvenation.

Thrombosis and inflammation, the primary causes of blood-contacting medical device failure, are initiated by interfacial biofouling. Although zwitterionic hydrogel coatings represent a promising solution, their clinical translation is hampered by the formidable challenge of simultaneously integrating mechanical robustness, high-strength substrate adhesion, and exceptional antifouling properties. Herein, we report a bioinspired zwitterionic hydrogel coating that overcomes this hurdle through a design combining microstructural alignment with multi-site chemical anchoring. The coating leverages cellulose nanocrystals (CNC) to induce an aligned microstructure that enhances antifouling through modulated interfacial hydrodynamics, while providing structural reinforcement for superior mechanical stability. An in situ multi-site chemical anchoring strategy is developed, enabling the coating to achieve an interfacial adhesion energy exceeding 800 J/m² on PVC substrates. Inspired by the vascular endothelium, the microstructure-aligned zwitterionic hydrogel coating significantly inhibits protein adsorption, platelet adhesion, and bacterial colonization. It retains outstanding stability even after 42 days of PBS shearing, 200 cycles of sandpaper abrasion, and 30 min of high-speed water flushing. Crucially, the coated PVC prevents biofilm formation and mitigates the foreign body response, while also inhibiting thrombus formation in an anticoagulant-free ex vivo rabbit circulatory model. This work lays the foundation for designing next-generation hemocompatible coatings for medical devices.

The cellular microenvironment plays a pivotal role in directing tissue development, repair, and homeostasis through a complex interplay of biochemical and mechanical cues. The extracellular matrix (ECM) serves as a key instructive component, guiding transcriptional programs that determine cell fate, function, and identity. In this study, we investigated the impact of microenvironmental context on the biofabrication of human skin equivalents, comparing constructs based on endogenous versus exogenous ECMs. Specifically, we compared collagen-based full-thickness skin models with full-thickness skin models based on a fibroblast-assembled endogenous ECM. Our RNA sequencing analyses reveal that ECM origin profoundly influences transcriptional trajectories, highlighting the importance of a native-like microenvironment in supporting appropriate gene expression profiles and morphogenetic processes. Notably, skin equivalents featuring endogenously produced ECMs exhibit physiologically relevant architecture, including a well-organized dermal-epidermal junction (DEJ), whereas constructs based on exogenous matrices, such as animal-derived collagen, display abnormal epithelial expansion and fail to replicate key structural features. These findings underscore the necessity of recapitulating the native ECM to achieve functional tissue constructs in vitro and raise critical considerations regarding scaffold choice in regenerative medicine and tissue engineering applications.

Accurate tumor detection and boundary delineation are crucial for effective management of gastrointestinal cancer. However, current methods like white light endoscopy (WLE) have limitations in precision, and existing fluorescent contrast agents suffer from rapid metabolism, limited tumor accumulation, and concerns regarding biological safety. In our study, we propose repurposing hematoporphyrin (HpD), a clinically approved photosensitizer for photodynamic therapy (PDT), as a potent fluorescent contrast agent for in vivo endomicroscopy. Our research represents the first demonstration of utilizing HpD fluorescence signals to provide valuable contrast for tissue microstructures over an extended period (50 scans). To address autofluorescence interference common in endomicroscopy, we developed an endomicroscopic fluorescence imaging system compatible with violet excitation, a crucial requirement for effective fluorescence imaging using hematoporphyrin. Our study showcased the effectiveness of the system in leveraging HpD's fluorescence for visualizing tissue microstructures, enabling clear differentiation between tumorous, inflammatory, and normal tissues based on unique texture patterns. The seamless integration of this system with PDT workflows allows for real-time tumor margin identification and treatment guidance through the same optical fiber bundle. This method not only serves as an effective supplement to WLE but also paves the way for more precise theranostics in tumor management.

Large maxillofacial bone defects severely impair oral function and aesthetics, and current treatments involving autologous bone grafting followed by prosthetic restoration are associated with high surgical trauma and prolonged rehabilitation. Herein, we present a tooth-bone integrated organoid (TBO) strategy that synchronously reconstructs bone and dental implant structures in vitro, aiming to achieve dual restoration of structure and function post-implantation. Bioactive glass (BG) was employed as a multifunctional "bond" that not only established effective adhesion between BG callus organoids and BG-Si₃N₄ implants via dual-interface bonding with soft and hard tissues, but also acted as an active stimulant and mineralization agent to accelerate the hypertrophy and ossification of callus organoids in the late stage of endochondral ossification. Simultaneously, BG enhanced the osteogenic potential and osseointegration of the dental implants through bioactive ion release and interfacial mineralization. This approach boldly confronts and attempts to resolve the dual challenges of maxillofacial bone defects repair and dental arch restoration, offering a clinically translatable pathway toward integrated structural and functional maxillofacial regeneration.

Advanced implantable medical devices often need to integrate multiple functions onto one surface to meet the complex needs in vivo. The construction of glycocalyx bionic coatings that mimic the natural multifunctional glycocalyx barrier of blood vessels, intestines, and ocular surfaces is an emerging strategy for function integration. However, in practical application scenarios such as corneal bandage lens (CBL) for corneal injury treatment, bio-enzymes from immune cells and bacteria can degrade the natural polymers constructing the glycocalyx bionic coating, such as hyaluronic acid, resulting in the loss of coating functionality. To address this issue, we propose an enzyme-resistant glycocalyx bionic coating (ER-GBC) strategy; by introducing baicalin as a hyaluronidase inhibitor into hyaluronic acid-based GBCs, the coating can be resistant to hyaluronidase's disruption. Meanwhile, by the free radical scavenging and bacteriostatic properties of baicalin and the bactericidal properties of silver nanoparticles embedded into the coating, the multiple functional ER-GBC of hydrophilic, anti-bacterial, and anti-inflammatory were realized. As a result, the ER-GBC-modified CBL achieved good therapeutic results in the rabbit model of bacterial keratitis. This ER-GBC strategy, constructed by combining glycocalyx active ingredients with corresponding enzyme inhibitors, is expected to provide new methods for developing bionic coatings for medical devices and clinical translation.

Coronary microvascular dysfunction (CMD) exhibits a high prevalence and is associated with adverse clinical outcomes, underscoring the critical importance of early detection. Early identification of CMD can significantly improve patient prognosis. This study aims to provide a novel strategy for the precise diagnosis of CMD during its early inflammatory phase. Focusing on this key inflammatory stage in the pathological progression, we sought to identify stage-specific molecular biomarkers. Through proteomic screening, we identified Nerve Injury-Induced Protein 1 (Ninj1). During the inflammatory response, Ninj1 promotes leukocyte migration and macrophage transendothelial migration, thereby influencing the trafficking and distribution of inflammatory cells. IR780 is a novel near-infrared (NIR) fluorescent agent characterized by excellent photostability and low toxicity. Loading IR780 onto nanoparticles enhances its in vivo biocompatibility and photostability while prolonging its circulation time. This project proposes a dual-modal molecular imaging probe targeting Ninj1 and loaded with IR780, which integrates NIR fluorescence and ultrasound imaging capabilities. This probe is designed to enable the early screening of CMD.

Wound healing is a complex physiological process that demands multifunctional therapeutic approaches to ensure effective recovery. This study presents a straightforward approach using blend electrospinning to produce multimodal hybrid nanomaterials that accelerate the wound healing process. Poly(L-lactide-co-ε-caprolactone) (PLCL), cellulose acetate (CA), and polyethylene oxide (PEO) were utilized as biodegradable, compatible, and compliant polymers for generating nanofibers. Hybrid nanofibers functionalized with dexamethasone, ascorbic acid, and hyperbranched polymers introduce anti-inflammatory, regenerative, and antimicrobial properties. Pristine nanofibers with diameters of 0.818 ± 0.028 and 0.845 ± 0.039 µm were generated, while drug-loaded fibers with average diameters of 1.075 ± 0.055 and 1.235 ± 0.075 µm were obtained. The fibers demonstrated a porosity ranging from 72 % to 86 %. Further, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), and contact angle, as well as zeta potential measurements, highlight the physicochemical properties of the fibers. In vivo studies of the nanofibers demonstrated that by day 11, there was a significant acceleration in wound healing. A remarkable acceleration was observed in cell proliferation, granulation, and remodeling phases. The findings emphasize the potential of multimodal hybrid nanofibers as advanced wound dressings and the importance of integrative strategies in wound care.

Although the idea of employing cell membrane biomimetic technologies for detecting circulating tumor cells (CTCs) promises paradigm-shifting advances in cancer diagnostics, its wide application is restricted by CTCs phenotypic variations. Current improvements primarily focus on optimizing biomimetic coatings to enhance capture efficiency, but there remains a significant gap between existing strategies and the practical demands of CTCs detection. Herein, a novel method considering the perspective of tumor cell modification was proposed, which involved concurrently modulating cellular chemical and mechanical properties. Specifically, the strategy employed metabolic glycoengineering to selectively remold tumor cells, thereby introducing artificial receptors into the tumor cell membrane. Additionally, Cytochalasin D, a drug that can interfere with the cytoskeleton, was used to alter the mechanical properties of the cell membrane, softening it and thereby significantly enhancing the contact area and adhesion ability between target cells and the substrate surface. To cope with the complex application environment, a visual biomimetic detection system was developed, leveraging the homologous targeting properties of the tumor cell biomimetic layer in combination with advanced colorimetric nanoprobes, enabling highly sensitive and specific detection of engineered CTCs. Overall, this approach adeptly circumvents challenges associated with biomarker bias, offering a robust method for non-invasive cancer diagnostics.