Biomaterials Science最新文献

Corneal defects pose a significant threat to visual function, underscoring the need for advanced transplantable artificial corneas. Collagen-based biomimetic scaffolds offer a promising avenue for corneal regeneration. However, the impact of collagen's hierarchical architecture on scaffold properties and its role in corneal healing remains incompletely understood. In this study, we systematically compared two distinct high-density collagen membranes: a fibrous collagen membrane (FCM), fabricated via thermally controlled vitrification to induce collagen self-assembly, and a non-fibrous collagen membrane (NFCM), prepared by chemical crosslinking followed by vitrification drying. The FCM dried at 37 °C exhibited well-aligned collagen fibrils and lamellar organization, along with thermal stability, hydration capacity, and mechanical behavior closely resembling those properties of the native cornea. In contrast, the NFCM, while mechanically brittle, possessed a smooth surface that markedly promoted epithelial cell migration. Leveraging these distinct properties, we constructed a bilayer collagen composite comprising an upper NFCM layer and a lower FCM layer, designed to synergistically facilitate rapid epithelial wound closure and robust stromal integration, respectively. Our findings underscore the pivotal role of collagen microstructure in determining the mechanical, optical, and biological performance of corneal scaffolds, and provide a rational design strategy for developing hierarchically structured collagen membrane composites with translational potential for corneal repair.

Photodynamic therapy (PDT), as a promising anticancer strategy, has attracted much attention due to the advantages of non-invasiveness, temporal-spatial selectivity, and low tendency to induce drug resistance. However, the clinical translation of PDT faces severe challenges, owing to the oxygen-demanding nature of ROS generation and the ultrashort lifespan and narrow diffusion radius of ROS. Herein, we report a nanoplatform that integrates a tumor microenvironment (TME)-responsive polymeric vehicle with an aggregation-induced emission (AIE) type-I photosensitizer (TD) with nucleus-targeting and DNA-binding abilities. This nanoplatform enables specific delivery in the acidic and GSH-overexpressed TME via pH/redox dual responsiveness, ensuring selective accumulation and low off-target effects. By mimicking the nucleus-targeting chemical structure of Hoechst, TD can penetrate the nuclear envelope, intercalate DNA, and generate hydroxyl radicals and superoxide anion radicals near genetic materials, causing DNA damage and apoptosis even under hypoxia. In vitro and in vivo studies confirmed the effective ROS generation, antitumor efficacy, and good biocompatibility of the nanoplatform. The DNA-binding-enhanced PDT strategy provides a promising pathway for precision phototherapeutics.

Titanium (Ti) is widely used in oral implants but is limited by insufficient osteogenic activity, angiogenic capacity, and antibacterial performance. To address this, pure Ti was modified by micro-arc oxidation (MAO) to form a porous layer, followed by magnetron sputtering of a TaCu nanocoating under different conditions to prepare three composite samples (MAO-Ti/TaCu1, MAO-Ti/TaCu4, and MAO-Ti/TaCu7). The samples were characterized for surface properties and Cu²⁺ release, and their biological performance was evaluated via in vitro experiments. Results showed that MAO-Ti/TaCu coatings maintained the MAO porous structure and achieved cytocompatible, sustained Cu²⁺ release. MAO-Ti/TaCu4 exhibited optimal osteogenic activity, with the highest cell viability, ALP activity, matrix mineralization, and expression of osteogenic-related genes (ALP, Runx2, Col-I, and OPN). MAO-Ti/TaCu7 showed the strongest angiogenic capacity, reflected by superior HUVEC morphology, migration, and angiogenic-related gene (eNOS, VEGF, and FGFR1) expression. All TaCu-modified groups had significant antibacterial activity. The enhanced performance was attributed to the synergistic effect of the porous MAO layer and TaCu nanocoating, with moderate Cu²⁺ release favoring osteogenesis and higher release promoting angiogenesis. This study provides a new strategy for titanium implant surface modification to improve osseointegration.

Intravesical therapy remains the standard treatment for non-muscle-invasive bladder cancer (NMIBC), yet its clinical efficacy is limited by significant biological, pharmacological, and procedural barriers. Conventional intravesical drug instillation requires repeated hospital visits and urethral catheterization, which may reduce patient compliance owing to discomfort, urethral trauma, and an increased risk of urinary tract infections. Therapeutic performance is further compromised by rapid drug dilution, frequent bladder emptying, and the dynamic urinary environment, resulting in a short intravesical residence time. Biological barriers, including the exceptionally tight urothelial permeability barrier (transepithelial electrical resistance >10 000 Ω cm²), comparable to the blood-brain barrier, and the hypoxic tumour microenvironment, further restrict drug penetration, leaving less than 5% of the administered dose available at the tumour site. Escalating drug concentrations to compensate for poor penetration frequently results in chemical cystitis and other local adverse effects. Among emerging biomaterials, chitosan has attracted considerable attention owing to its excellent mucoadhesive properties, transient modulation of urothelial tight junctions, favourable biocompatibility, and biodegradability, making it an attractive platform for prolonged intravesical drug retention. Genipin has emerged as the most widely investigated natural crosslinker because of its low cytotoxicity, tunable crosslinking properties, and ability to improve the mechanical stability and sustained-release behaviour of chitosan hydrogels. Integration of ultrasound as a non-invasive external stimulus, particularly through microbubble-mediated cavitation and sonoporation, further enables spatiotemporally controlled drug release and enhanced urothelial permeability. In this review, we critically discuss the biological barriers to intravesical drug delivery and highlight recent advances in ultrasound-responsive chitosan-genipin hydrogels as multifunctional platforms for NMIBC therapy. We evaluate crosslinker safety, strategies for overcoming tumour hypoxia, and preclinical evidence demonstrating prolonged bladder retention (>72 h), 2-3-fold enhanced tissue penetration, and tumour inhibition of 60-80%. Finally, we discuss key translational challenges, including scalable manufacturing, regulatory considerations, patient heterogeneity, and long-term safety, while outlining future opportunities in theranostic hydrogels, microrobots, closed-loop drug delivery, and multi-stimuli-responsive biomaterials. Collectively, ultrasound-responsive chitosan-genipin hydrogels represent a promising intravesical platform capable of enhancing therapeutic efficacy while minimizing treatment-related toxicity in NMIBC.

Recent advancements in experimental and computational methods along with growing gene sequencing libraries have enabled rapid development of nucleic acid-based therapeutic design for a wide variety of diseases. New drugs, delivery tools and methods have enabled precise and efficient therapy at a molecular scale. This review covers the current landscape and future directions of methods for gene and cell therapies, as well as their applications, advantages, and limitations. We present self-amplifying RNA, circular RNA, CRISPR systems, antisense oligonucleotides, and antibody-oligonucleotide conjugates, as well as CAR modification of T-cells, natural killer cells, and macrophages, with a brief discussion of modified stem cells. We also discuss developments in viral and non-viral delivery systems for their applications in cell and gene therapies.

Tunneling nanotubes (TNTs) are nano-scale intracellular conduits facilitating the transfer of cellular content. Intercellular communication between cancer cells via TNTs promotes invasion and metastasis. Given the important role of TNTs and macrophages in cancer, the role of macrophage-induced TNTs in the co-delivery of metformin (MET) and the chemotherapeutic drug doxorubicin (DOX) in mediating drug resistance is not fully understood. In this study, the inhibition of TNT-mediated breast cancer progression was mechanistically explored through DOX/MET co-delivery. For cargo delivery, the co-drugs were loaded onto gelatin and gum acacia. The DOX/MET co-loaded nanohydrogel induced the most substantial reduction in cell viability in MCF-7 breast cancer cells. The combination of DOX-MET resulted in the robust activation of caspase-3, indicating the enhanced execution of apoptosis. Upon internalization and lysosomal release, MET activates AMPK signaling, which in turn suppresses the PI3K/AKT/mTOR axis and inhibits TNT formation, thereby blocking intercellular communication. Concurrently, DOX localizes to the nucleus, where it disrupts DNA replication and directly induces cytotoxicity. This combined approach not only targets proliferative capacity but also dismantles cellular networking mechanisms. Overall, the results of this study endorse that this combined therapeutic strategy might offer enhanced efficacy in limiting breast cancer progression and metastasis through the inhibition of TNTs.

Atopic dermatitis is a serious, chronic inflammatory skin disease that can currently only be treated symptomatically. The rise in extracellular Ca²⁺ ions by mast cells and platelets, which acts as a death signal for neuronal cells, plays a crucial role in the pathogenesis of the disease. Both cell types produce the neurotransmitters histamine and serotonin and express the N-methyl-D-aspartate (NMDA) receptor on their surface. Here, we show that the physiological inorganic polymer polyphosphate (Na-polyP; when administered as the sodium salt), which is stored and released by platelets, can suppress the adverse effects in atopic dermatitis due to its unique ability to bind Ca²⁺ by coacervate formation. This eliminates the Ca²⁺ burst occurring in neural tissue damage by exchanging Na⁺ for Ca²⁺ ions. It is shown that the energy-rich Na-polyP, with a physiological chain length of approximately 50 phosphate residues, enhances the serotonin-induced neurite outgrowth in neuronal PC12 cells, even in the absence of the neurotransmitter and additional Ca²⁺ ions. In rat primary neuronal cells, Na-polyP completely prevented the histamine-caused apoptotic cell death. Based on the results of experiments with the indicator Fura 2-AM, which demonstrated an abolition of the histamine- and glutamate-induced rise in intracellular Ca²⁺ levels in neurons after addition of Na-polyP, we conclude that the neuroprotective effect of Na-polyP is due to the formation of polyP coacervate through Na⁺/Ca²⁺ exchange. Furthermore, it was found that Na-polyP enhances collagen fibrillogenesis, which is impaired in atopic dermatitis, as demonstrated by immunostaining and RT-qPCR experiments using human endothelial cells (HUVEC). The role of disease-relevant metalloproteinases induced by polyP was demonstrated in experiments with the inhibitor quercetin, using CD80 as a marker for pro-inflammatory M1 macrophages. Finally, studies in patients showed that Na-polyP embedded in a hydrogel can alleviate and heal atopic dermatitis lesions, indicating the potential of Na-polyP as a clinically applicable drug for treating the disease.

Immunotherapy has emerged as a new clinical paradigm for cancer management, leveraging immunomodulation to enhance systemic antitumor responses. Despite its significant potency and distinct advantages, challenges such as limited patient response rates and immune-related toxicities persist. Although nanomaterial-based delivery systems have been explored to improve local drug retention within tumor tissues, the efficacy of systemic nanomaterial strategies is constrained by low bioavailability and poor tumor penetration. As innovative localized delivery systems, injectable hydrogels hold significant promise in overcoming these challenges. Capitalizing on their inherent biocompatibility, tailorable physicochemical characteristics, and biomimetic interactions with the extracellular matrix, these hydrogel systems can be engineered to achieve precise therapeutic delivery with enhanced stability and bioavailability. Additionally, they enable the combination of immunotherapy with complementary treatment modalities, such as chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and oncolytic virotherapy. This review begins by outlining the key steps of the cancer-immunity cycle, along with existing immunotherapeutic approaches and their inherent limitations. Then, we outline the design principles of hydrogel-based therapeutic delivery systems for cancer immunotherapy. Additionally, it summarizes recent advances in developing functional hydrogels for the localized delivery of small molecules, macromolecules, and immune cells to elicit robust antitumor immune responses. Moreover, we explore the potential benefits of hydrogel-based combination immunotherapy in enhancing therapeutic outcomes. Finally, we discuss the critical challenges and future perspectives for the clinical translation of hydrogel-based cancer immunotherapies.

Engineering osteochondral scaffolds with continuous gradients remains a central challenge in regenerative medicine. Here, we present a one-step melt electrowriting (MEW) strategy to encode quasi-continuous compositional and structural gradients in poly(ε-caprolactone) (PCL) scaffolds. By sequentially loading nanohydroxyapatite (nHA)-laden PCL melts, a predefined mineral gradient is preserved during printing, yielding a continuous decrease in nHA content across the scaffold thickness. This gradient intrinsically drives a concomitant reduction in fiber diameter, thereby recapitulating the native transition from subchondral bone to cartilage. A porous TGF-β1-loaded hydrogel coating is further introduced to provide spatially relevant chondrogenic cues without compromising pore interconnectivity. The resulting scaffolds exhibit graded composition, structure, and mechanical properties, enabling coordinated osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro and promoting integrated osteochondral repair in vivo. This work establishes a generalizable MEW-based platform for single-step gradient encoding and offers a biomimetic design strategy for complex tissue interfaces.

Membrane fusion, a fundamental biological process enabling precise exchange of biomolecules within and between cells, has inspired the development of various fusogenic model systems for applications in drug delivery and beyond. However, conventional systems typically operate in an "always-on" state, lacking spatiotemporal control. Although cleavable polyethylene glycol coatings can confer temporal regulation through stimuli-responsive activation, such strategies are often unidirectional and synthetically challenging. Here, we report a simple yet reversible strategy to regulate liposomal membrane fusion via protonation of tertiary amines. By replacing the permanently positively charged lipid DOTAP with an ionizable analogue, DODAP, we constructed a pH-switchable fusogenic liposome (PsFul) that remains inactive at neutral pH but activates fusion upon protonation in acidic environments. This transition is fully reversible, allowing adaptive toggling between "on" and "off" states. We demonstrate that PsFul enables direct cytosolic delivery of anticancer drugs via membrane fusion, bypassing lysosomal entrapment and significantly enhancing cytotoxicity under acidic conditions. This work establishes a facile platform for achieving spatially and temporally controlled membrane fusion, offering promising potential for targeted therapeutic delivery.