Journal of Materials Chemistry B最新文献

Rheumatoid arthritis (RA), a chronic autoimmune disorder affecting 1% globally, urgently demands advanced therapies to overcome the systemic toxicity and limited efficacy of conventional glucocorticoids like dexamethasone (Dex). In this study, we constructed LMWH-Gly-Pro-ODA/Dex (LGPO/Dex) micelles, which synergistically integrate low molecular weight heparin (LMWH)-mediated active targeting with Gly-Pro-mediated fibroblast-activated protein (FAP)-α-responsive drug release to achieve spatiotemporal precision in RA treatment. The system operates through a three-stage cascade mechanism: (1) targeting the inflamed joints, (2) inflammation-responsive drug release to modulate pathological microenvironments (e.g., normalizing M1/M2 macrophage polarization), and (3) suppression of monocyte recruitment to prevent disease progression. LGPO/Dex micelles showed excellent RA therapeutic effects in the adjuvant-induced arthritis (AIA) model. Joint swelling, serum TNF-α, and nitric oxide (NO) levels in LGPO/Dex-treated rats showed no significant difference from healthy controls (ns) while exhibiting marked improvement over Dex monotherapy (**, P < 0.01). Notably, it also significantly reduced Dex-associated adverse effects. This study confirmed the feasibility of using FAP-α as a therapeutic target for RA and provided a new idea for RA treatment, offering a blueprint for disease-microenvironment-programmed therapeutics.

Magnesium phosphate (MgP)-based bioceramics have emerged as promising alternatives to bone substitutes; however, their rapid degradation and insufficient mechanical strength hinder their clinical applications. This study elucidated the fabrication, physicochemical properties, mechanical characteristics, and cytocompatibility of multiscale porous silicon-doped MgP scaffolds and decellularized platelet-rich fibrin (d-PRF) for application in critical-size bone defects. The scaffolds were fabricated through a cost-effective powder metallurgy route using naphthalene as a space holder (porosity: 6–51%). The findings revealed that the mechanical strength of the developed scaffolds ranged between 7 MPa and 56 MPa, similar to that of the human trabecular bone. A degradation study in a 7-day simulated body fluid (SBF) showed that the scaffolds with higher porosity (40 Naph) exhibited greater degradation (9–10% mass loss) and deposition of higher calcium (Ca) (0.24–0.26 wt%). The protein characterization of the synthesized d-PRF confirmed the presence of Aα polypeptide bands similar to human fibrinogen, and cell proliferation suggested that d-PRF has noncytotoxic and nontumorigenic effects on cells. When d-PRF was combined with the highly porous scaffolds (40 Naph), the cell proliferation significantly increased, possibly due to the sustainable release of d-PRF, leading to the prolonged stimulation of cell growth. In the in vivo evaluation, the scaffolds were bilaterally implanted into rabbit femoral condyle defects. After two months, radiographic, micro-CT, SEM-EDX, OTC labeling, and histological analyses demonstrated enhanced scaffold degradation, a radio-opacity resembling that of the host bone, increased osteogenesis, and improved collagen maturation in the 40 Naph + d-PRF scaffolds. Thus, the present study showed the synergistic effect of multiscale porosity (40 Naph) and d-PRF incorporation in Si-doped MgP scaffolds, making them promising candidates for bone tissue engineering applications.

Fluorinated polymers have emerged as a versatile class of materials for biomedical nanotechnology applications, owing to their unique physicochemical properties conferred by fluorination. The strong C–F bond, high hydrophobicity, low surface energy, and ability to modulate intermolecular interactions collectively endow self-assembled nanomaterials with enhanced stability, biocompatibility, and functional versatility. Over the past few decades, diverse fluorinated self-assembled architectures, including micelles, vesicles, liposomes, nanoparticles, and hydrogels, have been engineered for applications in drug delivery, gene therapy, bioimaging, antimicrobial therapy, tissue engineering, ophthalmology, and tissue bionics. Fluorination enables precise control over nanostructure assembly, improves barrier penetration, prolongs systemic circulation, enhances oxygen-carrying capacity, and supports imaging modalities. Moreover, tailored designs leverage fluorine's ability to resist protein adsorption, evade immune clearance, and promote targeted therapeutic effects under complex physiological conditions, including hypoxia and mucosal barriers. This review systematically discusses the structural characteristics, biomedical applications, and recent innovations in fluorinated polymer self-assembled nanomaterials, highlighting challenges such as potential environmental persistence and offering perspectives for sustainable development.

Cartilage tissue has a limited capacity for self-repair, making its regeneration a persistent challenge in orthopaedics. This has stimulated the development of tissue engineering strategies based on biomaterials. Gelatin, a collagen-derived biological macromolecule, has attracted considerable interest due to its excellent biocompatibility, tunable properties, and extracellular matrix (ECM)-mimicking characteristics. However, a systematic analysis of research trends in this field is currently lacking to guide future developments. This study employed bibliometric methods to quantitatively analyse 1276 publications from the Web of Science database between 2005 and 2025. Using tools such as VOSviewer, CiteSpace, and Bibliometrix, we mapped the technological evolution and collaborative networks in gelatin-based cartilage tissue engineering. Our analysis identified three distinct developmental phases: foundational materials development (2005–2012), stem cell regulation research (2013–2020), and the emergence of smart-responsive 4D bioprinting technologies (2021–2025). Four core research clusters were recognised: the evolution of biomaterials from static to smart-responsive systems, advanced control of stem cell microenvironments, innovations in spatiotemporal growth factor delivery, and the integration of 3D/4D printing technologies. Notably, “stem cell differentiation” consistently emerged as a key driving theme. Although China led in publication output (478 articles), its academic impact, measured by citation rates, lagged behind that of the Netherlands and the United States, indicating a “quantity-over-quality” imbalance. Beyond presenting objective bibliometric data, this study provides an in-depth technical review of current research advances. We systematically examined cutting-edge directions such as smart-responsive hydrogels, stem cell fate regulation, programmable drug delivery systems, and advanced bioprinting, highlighting a paradigm shift from passive support to active modulation in gelatin-based strategies. Considering the challenges in clinical translation, we propose strategic recommendations including standardised evaluation frameworks, complementary China–Europe collaboration models, and enhanced industry-academia-research synergy. These data-driven insights offer a scientific basis for resource allocation and technology roadmap planning, contributing to a shift in cartilage repair research from an “experience-driven” to a “data-informed” paradigm. This work establishes a systematic framework to advance translatable cartilage repair strategies.

The hydrochalcone derivative MF-15 and the synthetically derived BRP-201 are potent anti-inflammatory active pharmaceutical ingredients (APIs) that suffer from poor bioavailability. This necessitates their incorporation into drug delivery systems. To address this limitation, we investigated four polymeric carrier materials. The poly(ester amide)s poly(3-benzylmorpholine-2,5-dione) (PPheG) and poly(3-isopropyl-morpholine-2,5-dione) (PValG), the benchmark poly(lactic-co-glycolic acid) (PLGA), and the polysaccharide acetalated dextran (Ac-Dex) were used to formulate nanoparticles via nanoprecipitation. The nanoparticles had sizes of around 110 to 190 nm with negative zeta potentials. Although atomistic molecular dynamics (MD) simulations predicted enhanced miscibility of PPheG and PValG with MF-15, the highest loading capacity was achieved with Ac-Dex (4.2 wt%). None of the MF-15-loaded particles elicited a biologic response (i.e., 15-lipoxygenase (LOX)-1 activation) in human M2 monocyte-derived macrophages (MDMs). The consistent failure across all MF-15 formulations, despite differences in polymer composition, drug loading, and enzymatic degradation profiles, suggests that encapsulation inherently interferes with MF-15's ability to activate 15-LOX-1, irrespective of the carrier system. In contrast, all BRP-201-loaded formulations demonstrated potent anti-inflammatory effects in human neutrophils. Overall, our findings demonstrate that polymer–drug miscibility and favorable physicochemical properties alone are insufficient to predict in vitro efficacy, highlighting the importance of kinetic and formulation-dependent factors in the successful delivery of anti-inflammatory agents.

Wound healing is a complex and dynamic biological process, and impaired healing can lead to prolonged recovery and increased healthcare costs. Recent advancements in wound healing therapeutics include hydrogel-based biomaterials, nanocarrier-mediated drug delivery systems, and tissue-engineered scaffolds that aim to modulate the wound microenvironment and accelerate tissue regeneration. However, wound healing remains a clinical challenge, particularly when sustained delivery of therapeutic agents and conformal wound coverage are required. Herein, we develop a multifunctional hydrogel system composed of hyaluronic acid modified with methacrylate and a zirconium-based metal–organic framework (MOF), enabling enhanced structural control and drug retention. The resulting hydrogel exhibits tunable photo-crosslinking kinetics, allowing precise gelation behavior and extrusion-based 3D printing without the need for a support bath. Moreover, the integration of hydrophobic and rigid MOF particles significantly suppresses water uptake, imparting anti-swelling properties that facilitate the sustained release of hydrophobic drugs such as quercetin. When applied to a wound healing model, the proposed platform promotes fibroblast migration and tissue regeneration over an extended period, highlighting the therapeutic potential of controlled drug release. Thus, this hydrogel offers a structurally robust, printable, and drug-releasing biomaterial platform for next-generation wound dressings.

Mitochondria targeting has been extensively reported in cancer therapy. Nevertheless, damaging mitochondria alone does not yield excellent efficacy, making it a challenge in the effective treatment of cancer metastasis. Inspired by the close relationship between mitochondria and microtubules in location and function, we propose an active-targeting nano-system that consists of a mitochondrial-damaging drug and a microtubule stabilizer. The nano-system exhibits synergistic cytotoxicity and effectively inhibits the migration and invasion of tumor cells more than either damaging mitochondria or stabilizing microtubules alone in vitro. In vivo experiments also reveal a remarkable suppression of over 85% of lung metastasis by the nano-system. Further mechanism investigations unravel mitochondrial damage by up-regulated reactive oxygen species and down-regulated adenosine triphosphate. Along with microtubule stabilization, mitochondrial fission is suppressed, further promoting mitochondrial damage. Subsequently, the nano-system jointly suppresses the epithelial–mesenchymal transition process and reduces the expression of metastasis-associated proteins to exert the anti-metastasis effect. Overall, mitochondrial damage combined with microtubule stabilization scales new heights in anti-metastasis efficacy, indicating that this combination strategy is a potential therapy for cancer metastasis.

Alzheimer's disease (AD) is primarily associated with the aggregation of amyloid-β (Aβ) due to insufficient clearance of Aβ peptides. This leads to deposition of fibrillar Aβ (fAβ), contributing to AD progression. Microglia, the brain's resident immune cells, are central to the phagocytotic-fusion of fAβ. Notably, fAβ itself can activate microglia via toll-like receptor signaling, triggering a phagocytic response. Previous studies have shown that activated microglia exhibit efficient phagocytotic-fusion of fAβ, primarily through lysosomal acidification compared to resting microglia. Therefore, distinguishing microglial activation states is vital for understanding and potentially modulating Aβ clearance mechanisms in AD. Herein, we systematically modified the structure to develop fluorescent probes (FPs), PS-Mor and PM-DMor based on morpholine-conjugated pyrylium and pyridinium derivatives of indigenous “IndiFluors”. These probes exhibit strong fluorescence enhancement in lysosomal pH windows by modulating photoinduced electron transfer (PET). The turn-on behavior of the probes was further supported by TD-DFT/PCM theoretical calculations. Confocal imaging revealed that PM-DMor selectively localizes to lysosomes, while PS-Mor targets mitochondria in activated human microglia. PM-DMor effectively monitors intracellular pH changes (ΔpHi) during drug-induced apoptosis and discriminates activated from resting microglial using both fluorescence microscopy and flow cytometry. Importantly, PM-DMor also tracks Aβ-induced microglial activation and subsequent phagocytosis of Aβ. Overall, PM-DMor offers a valuable tool for probing lysosomal dynamics in microglia and holds promise for early-stage therapeutic strategies targeting Aβ clearance in Alzheimer's disease.

Since the discovery of bioactive glasses (BAGs), extensive research has been performed to refine their biological properties and enhance their regenerative potential. Progress in this field has not only focused on tailoring BAGs compositions and creating new synthesis methods but also addressed their association with other therapeutic agents. These associative strategies aim to provide multifunctional biomaterials and elicit synergistic/complementary biological effects that accelerate tissue repair and address a wide range of complex regenerative microenvironments (infection, oxidative stress, etc.). Among these approaches, the combination of ion-doped BAGs with natural polyphenols (PPhs) has shown significant potential in bone regeneration, wound healing, and cancer treatment. This review provides a comprehensive analysis of the BAGs–PPhs hybrid systems, detailing the various methods used for their association and the underlying mechanisms and factors governing BAGs and PPhs interactions. In addition, particular attention is given to how these interactions affect the release and prolong the bioavailability and reactivity of natural PPhs. This review discusses the effect of BAGs–PPhs coupling on BAGs’ apatite forming ability and PPhs' antioxidant properties, and highlights key in vitro cellular findings on the osteogenic, angiogenic, immunomodulatory and cancer suppressive properties of BAGs–PPhs constructs, which are supported with in vivo evidence on therapeutic potential of these biomaterials. By offering an overview of the current advancements in this field, this review not only underscores the biomedical relevance of BAGs and PPhs coupling but also outlines existing challenges and identifies research perspectives for accelerating the translation of these biomaterials into clinical applications.

Colorectal cancer (CRC) mutations drive resistance and poor prognosis, underscoring the need for more effective therapies. The oxidative drug therapy combining arsenic trioxide (ATO) and D-vitamin C (D-VC) has demonstrated promising efficacy by targeting mitochondrial functions and depleting antioxidant defences to induce apoptosis in CRC cells. ATO and D-VC create a hostile environment for cancer cells by simultaneously targeting mitochondrial metabolism and redox homeostasis, reducing their ability to adapt and survive. This study evaluated the cytotoxic effects of ATO/D-VC in 2D cell cultures and 3D cell models, known as clusteroids, generated from CRC cell lines HCT116 and SW620. In the 2D cultures, the ATO/D-VC combination significantly reduced cell proliferation to 40–60% and viability to below 30% of control levels. In contrast, clusteroids showed a more limited response, with proliferation reduced to 60–80% and viability to 80–90%, highlighting the impact of the extracellular matrix (ECM) and cell–cell interactions in limiting drug diffusion within structured tumour microenvironments. To overcome these drug diffusion barriers, ATO and D-VC were individually encapsulated in poloxamer-stabilized shellac-based nanoparticles (NPs) surface functionalized with Savinase, a protease known to degrade ECM components. The cell viability and cell proliferation assays demonstrated that nanoparticle-mediated delivery significantly enhanced treatment efficacy in clusteroids. Dual treatment of Savinase-coated ATO and D-VC loaded NPs caused pronounced disruption of clusteroid morphology and substantially reduced both viability and proliferation to approximately 30–40% of untreated control levels. Compared to the free drug and uncoated nanoparticle formulations, the Savinase-functionalized nanoparticle formulation achieved nearly twice the reduction in viability and proliferation, indicating a marked improvement in therapeutic effect. Unloaded Savinase-coated nanoparticles showed minimal impact, underscoring their biocompatibility. This approach demonstrates the potential of protease-functionalized nanoparticles to enhance the oxidative drug delivery and efficacy in CRC tumours and could potentially allow targeting the therapeutic resistance in other solid tumours with dense ECM barriers.