Advanced Healthcare Materials最新文献

Sepsis is an underappreciated yet severe threat to human life, marked by organ dysfunction and high mortality resulting from disordered inflammatory responses to blood infection. Unfortunately, no specific drugs are available for effective sepsis treatment. As a pivotal biomarker for sepsis, lactate levels are closely related to vascular permeability and sepsis-associated mortality. Herein, a dual-pipeline lactate removal strategy is reported from circulating blood to ameliorate vascular permeability and lipopolysaccharide (LPS)-induced sepsis. This is achieved by formulating lactate oxidase (LOX)-encapsulated hollow manganese dioxide (HMnO₂) nanohybrids (LOX@HMnO₂-P[5]A) bearing pillar[5]arene (P[5]A) macrocycle with excellent host-guest properties. The highly biocompatible nanohybrids enable direct lactate consumption through LOX catalytic degradation and block lactate production by P[5]A-mediated LPS trapping, allowing for dual-pipeline lactate removal to maximize the reversal of lactate-mediated vascular hyperpermeability. Besides, HMnO₂ cores decompose hydrogen peroxide produced from lactate oxidation into oxygen, further contributing to lactate consumption and mitigating the hypoxic inflammatory environment. In vivo investigations demonstrate that intravenous administration of LOX@HMnO₂-P[5]A nanohybrids with extended blood circulation can effectively ameliorate endothelial barrier dysfunction, inflammatory responses, and multiple organ injury, ultimately improving survival outcomes in LPS-induced sepsis. Taken together, this dual-pipeline lactate removal strategy offers a promising approach for efficient sepsis treatment.

Multifunctional hydrogels hold significant promise for promoting the healing of infected wounds but often fall short in inhibiting antibiotic-resistant pathogens, and their clinical translation is limited by complex preparation processes and high costs. In this study, a multifunctional hydrogel is developed by combining metal-phenolic networks (MPNs) formed by tannic acid (TA) and gallium ions (Ga³⁺) with chitosan (CS) through a simple one-step method. The resulting CS-TA-Ga³⁺ (CTG) hydrogel is cost-effective and exhibits desirable properties, including injectability, self-healing, pH responsiveness, hemostasis, antioxidant, anti-inflammatory, and antibacterial activities. Importantly, the CTG hydrogels are effective against antibiotic-resistant pathogens due to the unique antibacterial mechanism of Ga³⁺. In vivo studies demonstrate that the CTG hydrogel promotes follicle formation and collagen deposition, accelerating the healing of infected wounds by inhibiting blood loss, suppressing bacterial growth, and modulating the inflammatory microenvironment. These findings highlight the CTG hydrogel's potential as an advanced and translational dressing for enhancing the healing of infected wounds.

Vascular hypo-fibrinolysis is a historically underappreciated and understudied aspect of venous thromboembolism (VTE). This paper describes the development of a micro-clot dissolution assay for quantifying the fibrinolytic capacity of endothelial cells - a key driver of VTE development. This assay is enabled using aqueous two-phase systems (ATPS) to bioprint microscale fibrin clots over human umbilical vein endothelial cells (HUVECs). Importantly, these micro-clots are orders of magnitude smaller than conventional fibrin constructs and allow HUVEC-produced plasminogen activators to mediate visually quantifiable fibrinolysis. Using live-cell time-lapse imaging, micro-clot dissolution by HUVECs is tracked, and fibrinolysis kinetics are quantified. The sensitivity of cell-driven fibrinolysis to various stimuli is rapidly tested. The physiological relevance of this convenient high-throughput assay is illustrated through treatments with lipopolysaccharide (LPS) and rosuvastatin that elicit anti- and pro-fibrinolytic responses, respectively. Furthermore, treatment with baricitinib, an anti-inflammatory therapeutic found to increase cardiovascular risks after market approval, provokes an anti-fibrinolytic response - which highlights the potential role of endothelial cells in increasing VTE risk for patients receiving this drug. This endothelial cell fibrinolysis assay provides a high-throughput and versatile drug testing platform - potentially allowing for early preclinical identification of therapeutics that may beneficially enhance or adversely impair endothelial fibrinolysis.

Neointimal hyperplasia, a pathological response to arterial interventions or injury, often leads to restenosis and recurrent narrowing or occlusion, particularly in the peripheral vasculature. Its prevalence and negative impact on the long-term success of vascular interventions have driven extensive research aimed at better understanding the condition and developing effective therapies. This review provides a comprehensive overview of emerging bioengineering strategies for treating neointimal hyperplasia in peripheral vessels. These approaches include novel therapeutics and cell-based technologies designed to promote re-endothelialization, modulate vascular smooth muscle cell (VSMC) phenotype, reduce inflammation, scavenge reactive oxygen species (ROS), and enhance biomechanical compatibility between grafts and native vessels. Furthermore, advanced therapeutic delivery modalities are highlighted for their potential to achieve targeted, localized treatment at injury sites. This review also explores underrepresented therapeutic targets beyond traditional approaches, offering new opportunities for intervention. The multifaceted examination underscores the challenge of neointimal hyperplasia and presents a promising roadmap toward more effective treatments, ultimately aiming to improve patient outcomes after vascular interventions.

Volumetric muscle loss (VML) refers to muscle tissue loss exceeding 20% within a functional area due to trauma or surgery, often leading to physical disabilities. VML treatment relies on the transplantation of autologous flaps harvested from a healthy-donor site while minimizing the probability of immune rejection. However, this approach often leads to donor-site morbidity and relies on a restricted supply of muscle tissue. Current solutions in tissue engineering focus on engineered grafts lacking hierarchical vasculature with a feeding vessel, thus limited by diffusion. This study expanded upon a new approach of multimodal bioprinting which enabled the fabrication of thick hierarchical vascular muscle flaps composed of bioprinted and vascularized skeletal muscle tissue, and a 3D-printed engineered macrovessel, which successfully repaired VML injury in-vivo. The flaps are implanted by anastomosing the macrovessel via microsurgery to the femoral artery in proximity to an induced VML injury in Sprague-Dawley rat hindlimbs. Immediate perfusion of the flaps is demonstrated, as is flap endurance to physiological blood pressure, flow, and shear stress. Flap implantation enhanced myocyte differentiation, and vascular ingrowth and facilitated tissue viability and integration. These results obtained by utilizing human-origin cells provide a foundation for fabricating patient-specific flaps for the treatment of extensive soft tissue defects.

Current early cancer diagnostic technologies, such as imaging, molecular tests, endoscopic techniques, and biopsies, face considerable challenges in low-and middle-income countries (LMICs) due to high costs, procedural complexity, and limited resource access. Microneedle-based liquid biopsy for skin interstitial fluid (ISF) offers a practical and minimally invasive alternative for cancer diagnosis in these settings. This review systematically examines ISF liquid biopsy methods for their effectiveness in capturing cancer biomarkers directly from the skin and assesses their potential to address diagnostic needs in low-resource environments. Recent innovations in microneedle design and ISF underscore their potential in enabling early, accessible cancer detection tailored to LMICs' needs. Additionally, integrating artificial intelligence (AI) for data interpretation is proposed as a way to enhance diagnostic accuracy and enable real-time point-of-care (POC) applications. Collectively, these advances illustrate a flexible, scalable model for accessible cancer diagnostics, with significant implications for improving early detection and healthcare quality in resource-limited environments.

Developing nanoscale platforms with high integration, assembly efficiency, and structural stability for performing complex computations in specific cells remains a significant challenge. To address this, the Three-dimensional Hierarchical Octahedral Robotic (THOR) DNA nanoplatform is introduced, which integrates targeting, logic computation, and sensing modules within a single framework. This nanoplatform specifically binds to cancer cell surface proteins, releasing aptamer-linked fuel chains to initiate subsequent computational processes. Three logic gates efficiently compute any arbitrary binary combination of target proteins. The sensing module employs catalytic hairpin assembly for detecting specific miRNAs with high sensitivity. THOR demonstrates robust functionality both in vitro and in situ. As a proof-of-concept, this nanoplatform to distinguish acute lymphoblastic leukemia (ALL) patients from other leukemia subtypes and healthy participants, achieving 100% accuracy is applied. Additionally, this approach reliably monitored the therapeutic progress of ALL patients, showing strong concordance with bone marrow smear results. The THOR platform highlights the feasibility of constructing a reliable, hierarchical, and multifunctional analytical system based on a single DNA polyhedron. It offers a promising auxiliary tool for clinical diagnostics and therapeutic monitoring.

Platelet-rich plasma (PRP) is characterized by elevated concentrations of growth factors that facilitate bone repair. Nonetheless, the effective integration of PRP with bone implants and the sustained release of its active constituents pose significant challenges. In this study, thrombin is grafted onto the surface of polyetheretherketone (PEEK) via an N,N'-Disuccinimidyl Carbonate (DSC) linker and the retained enzymatic activity of thrombin enables the controlled activation of PRP self-assembly, resulting in the formation of a functional bio-gel layer. The optimal thrombin concentration to be 100 U/ mL^-1 is determined, at which point both the grafting amount and enzymatic activity of thrombin reaches their peak, with no further increases observed at higher concentrations. PRP solutions with varying platelet enrichment ratios are subsequently activated on the thrombin-grafted PEEK surface, yielding self-assembled bio-gels capable of sustained growth factor release for up to 16 days. The thrombin-activated PRP bio-gel on PEEK surface not only enhances in vitro cell adhesion, proliferation, osteogenic differentiation, vascularization and specific polarization of macrophages, but also effectively facilitates in vivo angiogenesis, immunomodulation and bone formation in a platelet dose-dependent manner. Consequently, the thrombin-activated PRP gel presents a promising strategy for the biological functionalization of PEEK implants in orthopedic applications.

The intricate morphology, physicochemical properties, and interacting proteins of lipid droplets (LDs) are associated with cell metabolism and related diseases. To uncover these layers of information, a solvatochromic and photosensitized LDs-targeted probe based on the furan-based D-D-π-A scaffold is developed to offer the following integrated functions. First, the turn-on fluorescence of the probe upon selectively binding to LDs allows for direct visualization of their location and morphology. Second, its solvatochromic fluorescence with linear correlation to polarity quantifies micro-environmental heterogeneity among LDs. Third, the unique photosensitized properties enable photocatalytic proximity labeling and enrichment of LDs-interacting proteins, ready for potential downstream proteomic analysis. These functions are exemplified using artificial LDs in buffer, stressed liver cell line, and diseased liver tissues biopsied from patients. While most LD sensors only offer fluorescence imaging functions, the multi-functional LD probe reported herein integrates both singlet fluorescence and triplet photosensitization properties for LDs studies.

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.