Advanced Healthcare Materials最新文献

Uncontrolled bleeding in trauma and surgical settings requires rapid, minimally invasive materials that can effectively stop bleeding and provide durable wound sealing. Here, we introduce an injectable, pH-responsive amphiphilic hydrogel designed for quick hemostasis, strong wet-tissue adhesion, and controlled therapeutic release. The hydrogel is prepared via a mild nucleophilic substitution reaction between tertiary amines of Poly(2-(dimethylamino)ethyl methacrylate (PDMA) and gallic acidfunctionalized branched polyethyleneimine PEI(GA), using chloride-terminated Pluronic F-127 (Cl-Plu-Cl) as a crosslinker. The shear-thinning, uniform prepolymer allows for consistent laparoscopic delivery and rapidly gels in situ (∼54 seconds) across a physiological pH range (5.07.4). In vitro and in vivo tests, including a mouse liver hemorrhage model, showed a 61% reduction in blood loss, comparable to Truseal (∼63%), while providing better injectability, biocompatibility, flexibility, and adjustable degradation and gelation properties. The (Cl-Plu-Cl/PDMA/PEI(GA)) hydrogel demonstrates strong adhesion strength (∼47 kPa) and withstands burst pressures up to 220 mmHg, exceeding typical arterial blood pressure. Sustained, pH-responsive release of amoxicillin (∼60% at pH 7.4 and ∼98% at pH 5.0 over 80 hours) displayed antibacterial activity against Staphylococcus aureus and MRSA. Alamar Blue and Live/Dead assays confirmed over 90% cell viability, and the gradual in vitro degradation over three weeks indicates safe resorption and potential for clinical use.

Bacterial infection and oxidative stress at wound sites can significantly impede the wound healing process. Curcumin, a versatile and abundant natural product, exhibits broad-spectrum antibacterial and antioxidant properties and is under investigation as a promising wound healing agent. However, its inherent limitations, such as low water solubility and bioavailability, hamper its clinical applications. To overcome these challenges and improve biosafety, the development of nanoparticulate curcumin formulation has emerged as a promising strategy. Herein, a curcumin‑based metal-organic framework (Cu/Zn-Cur MOF) was fabricated using a facile and efficient "mixing-diluting" strategy, achieving precise control over particle size through straightforward concentration adjustments of the curcumin-metal ion (Zn²⁺, Cu²⁺) complex. The resulting Cu/Zn-Cur MOFs, which exhibit a well-distributed spherical morphology, demonstrate admirable antioxidant activity by effectively eliminating •OH and •O₂ ^- radicals. Additionally, Cu/Zn-Cur MOFs display broad-spectrum and robust antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, Cu/Zn-Cur MOFs were integrated into a tissue adhesive hydrogel to form a multifunctional wound dressing (PCEM). In vivo studies demonstrated that the biocompatible PCEM exhibited good therapeutic efficacy and promoted infected wound healing. Overall, this work reports a novel strategy for the synthesis of carrier-free curcumin nanoparticles, providing an avenue to broaden the application of insoluble natural active polyphenols.

Intervertebral disc degeneration (IVDD) is a common condition causing chronic back pain and functional impairment, which severely reduces patients' quality of life. Traditional treatments only relieve symptoms without addressing the underlying pathology, highlighting the need for new therapies that repair IVDD at a mechanistic level. Recent progress shows biomaterials can support structure and boost tissue regeneration by mimicking the native extracellular matrix (ECM) of the nucleus pulposus. They also act as delivery systems for bioactive molecules, extending their retention at the target site to enhance efficacy. Meanwhile, noncoding RNA (ncRNA) regulates IVDD pathogenesis by modifying genes linked to inflammation, cellular homeostasis, and ECM metabolism, opening new avenues for gene therapy. Thus, combining biomaterials with ncRNA delivery creates a synergistic IVDD treatment. Over the past decade, research has focused on designing nanoparticles to encapsulate ncRNAs, enabling precise targeting of specific cells in degenerated discs. This study outlines IVDD's physiological/pathological features, existing therapies and their limits, and recent advances in biomaterials and ncRNA for IVDD treatment. We propose that future research should develop multifunctional biomaterial platforms that provide structural support and targeted gene therapy to improve disc regeneration and clinical outcomes for IVDD patients.

Recent advancements in photodynamic therapy (PDT) have highlighted its potential as a non-invasive cancer treatment. However, to fully realize the clinical potential of PDT, the development of innovative photosensitizers is essential. In this study, efficient heavy-atom-free PSs (IR820-1-3) activated by 808 nm light irradiation were developed by incorporating electron-rich/sterically bulky groups at the meso-position of the IR820 scaffold, a novel indocyanine green derivative. Notably, experimental results and transient absorption spectroscopic studies indicated that substituent bulkiness plays a key role in promoting reactive oxygen species (ROS) generation. IR820-3 PS, with a highly twisted molecular structure, demonstrated superior ROS production via both type I and type II photochemical pathways. The self-assembled nanostructure of IR820-3 underwent partial disassembly upon interaction with albumin, resulting in enhanced fluorescence intensity and photodynamic efficiency. Interestingly, the cationic cyanine backbone facilitated the mitochondria-specific localization of IR820-3, which further contributed to IR820-3's effective PDT performance against cancer cells. Importantly, in vivo findings indicated that the IR820-3 exhibited excellent tumor-targeting ability and induced efficient tumor photoablation under 808 nm NIR irradiation. This study provides insights into the molecular design of a facile, "one-for-all" NIR photosensitizer based on a heptamethine cyanine platform, highlighting its potential for preclinical and clinical applications.

Sickle cell disease (SCD), a monogenic disorder arising from a single point mutation in the β-globin gene, continues to pose a significant global health burden despite advances in supportive care. This mutation drives the formation of hemoglobin S (HbS) polymers under deoxygenated conditions, causing erythrocyte sickling, vaso-occlusive crises, and multi-organ complications. Current therapies, such as hydroxyurea and voxelotor, provide only partial symptomatic relief, underscoring the urgent need for transformative strategies. This review highlights the molecular glue paradigm, a novel approach that repurposes hemoglobin itself as a therapeutic scaffold. By integrating high-resolution structural insights from cryo-electron microscopy and predictive modeling via artificial intelligence, engineered hemoglobin variants can be rationally designed to inhibit polymerization, stabilizing non-pathogenic conformations and preventing fiber formation. These molecular glues, generated through gene editing or synthetic biology, offer a cell-intrinsic, high-concentration mechanism to counteract HbS polymerization, potentially overcoming the limitations of current therapies. We examine the key challenges in translating this paradigm, including precise structural characterization of polymerization intermediates, efficient intracellular delivery to erythrocytes, temporal regulation under hypoxic conditions, and the mitigation of immunogenicity.

Rejection following heart transplantation remains a significant challenge in the medical science. In addition to the immune response, the inflammatory response and microvascular endothelial damage can exacerbate rejection; however, current therapies focus primarily on the immune response. Numerous studies have confirmed that miR-126 regulates vascular inflammation and promotes angiogenesis. To achieve the precise targeted delivery of miR-126, macrophage biomimetic ultrasound phase-change cationic nanoparticles carrying miR-126 (miR-126-MCNPs) are synthesized. Incorporation of the macrophage membrane enhances the anti-phagocytic and inflammatory targeting of nanoparticles, thereby prolonging the circulation time and promoting aggregation in the transplanted heart. Using ultrasound-targeted microbubble destruction (UTMD), the perfluoropentane nanoparticle core undergoes a phase change in the ultrasound irradiation zone, allowing the targeted delivery of macrophage membranes and miR-126, and significantly improving the transfection efficiency of the miR-126. Consequently, anti-inflammatory effects are achieved, such as inhibition of macrophage and CD3⁺ T cells infiltration, and alteration of M2-type macrophage differentiation. In addition, this study demonstrates that the combination of miR-126-MCNPs with UTMD can alleviate the extent of vascular endothelial and interstitial fibrosis in transplanted hearts, increase angiogenesis, and improve microcirculation and cardiac function. This research provides a new strategy for the precision-targeted therapy of cardiac transplant rejection.

Ovarian cancer (OvCa) remains a leading cause of gynecological cancer mortality, particularly due to its aggressive peritoneal metastasis. Conventional treatments, including surgery and paclitaxel-based chemotherapy, are often limited by poor drug penetration into solid tumors, multidrug resistance, and the highly immunosuppressive tumor microenvironment. To overcome these challenges, we engineered a novel bacteria membrane-fused biomimetic paclitaxel liposome (PLip@DMV) by incorporating bacteria membrane-derived vesicles from attenuated Salmonella VNP20009. Administered via intraperitoneal injection, PLip@DMV not only delivered paclitaxel effectively but also leveraged the immunomodulatory properties of the Salmonella membrane. This led to significant antitumor immune activation within the metastatic tumor microenvironment, synergistically enhancing therapeutic efficacy and markedly prolonging the survival of tumor-bearing mice. Furthermore, the enhanced delivery efficiency and sustained-release characteristics of PLip@DMV resulted in significantly reduced systemic toxicity and tissue accumulation compared to free paclitaxel. Our findings demonstrate that PLip@DMV represents a more efficient, safer, and immunologically potentiated strategy for treating peritoneal metastatic ovarian cancer. This novel biomimetic nanocarrier holds significant promise for improving clinical outcomes in advanced OvCa.

Impaired diabetic wound healing is driven by immune dysregulation and microenvironmental disruptions induced by hyperglycemia, leading to excessive inflammation and defective macrophage polarization. Although macrophage extracellular traps (METs) play critical roles in chronic inflammatory diseases, their involvement in shaping the diabetic wound immune microenvironment and impeding macrophage polarization remains insufficiently understood. Here, we present zinc-containing bioactive glass (ZnBG), in which zinc incorporation confers immunomodulatory properties. In a type 2 diabetic full-thickness skin excision model, ZnBG significantly mitigates MET-associated oxidative stress and inflammation. Mechanistic investigations reveal that ZnBG effectively suppresses MET formation by reducing reactive oxygen species levels, inhibiting PAD4 activation, and blocking the NLRP3/caspase-1/GSDMD signaling pathway. Consequently, ZnBG facilitates macrophage transition from the pro-inflammatory M1 phenotype to the reparative M2 phenotype in diabetic wounds, thereby alleviating inflammation, enhancing neovascularization, and ultimately promoting diabetic wound healing. These findings provide an innovative therapeutic strategy that integrates ZnBG with targeted modulation of macrophage function for the treatment of diabetic wounds.

Effective resource-constrained volumetric ultrasound imaging requires compact, low-power systems capable of wide-angle real-time 3D imaging to accommodate small changes in placement by the operator. However, obtaining such images requires an excessive O(N²) channel count, bulky electronics, and high power consumption. We introduce an end-to-end system architecture to enable high-resolution, real-time 3D ultrasound imaging in a portable form factor. We present: a convolutional optimally distributed array (CODA) geometry that drastically reduces the number of elements (from 1024 to 128), a novel chirped data acquisition (cDAQ) architecture that enhances imaging depth while operating with a 25.3 dB lower transmit amplitude than a pulsed system, and an associated new signal processing methodology. We experimentally demonstrate our system's ability to perform deep (> 11 cm), high axial resolution (< 600 µm), and wide-angle (57°) imaging, while simultaneously reducing power consumption (29.6x reduction) and drive voltage (18 V). We validated our system in vitro and further performed in vivo human trials, demonstrating the ability to detect both tumors and cysts in breast tissue. This new architectural approach will unlock a new class of medical devices with enhanced diagnostic and long-term monitoring capabilities and open up future wearable designs of real-time 3D ultrasound systems.