Biomaterials最新文献

Corneal alkali burns cause persistent inflammation, leading to corneal vascularization and fibrosis, which severely impair vision. Here, we developed a temporary adhesive and detachable Janus silk-based patch to capture and remove inflammatory mediators from the ocular surface. The lower silk layer of the Janus patch incorporates of polyamidoamine and heparin, offering adsorption capacity for inflammatory mediators on the ocular surface. The upper hyaluronan layer imparts lubrication, alleviating foreign-body sensation and reducing shear stress from blinking. The integration of the silk and hyaluronan layers is achieved through interfacial diffusion, liquid-liquid phase separation, and photopolymerization, resulting in a stable interpenetrating network interface. After water annealing, the Janus patch exhibited excellent transparency, mechanical strength, and swelling resistance, remaining attached to the rat ocular surface for 3-5 days. Adsorption tests confirmed that the patch effectively captured small-molecule dyes, proteins, and free DNA. In the rat corneal alkali burn model, imaging and histological evaluations showed significant reductions in vascularization and fibrosis after 3 days of treatment, along with improved corneal transparency. RNA sequencing revealed that patch treatment effectively inhibited the PI3K-AKT inflammatory pathway. This inflammation-removing patch represents an innovative treatment for corneal alkali burns with significant clinical potential.

Three-dimensional (3D) scaffold-based culture systems offer a promising approach for expanding primary hepatocytes in vitro, potentially overcoming donor shortages in liver failure treatment. In this study, we designed a multifunctional Alg1SBC scaffold that actively loads and activates platelet-rich plasma (PRP) as a bioinspired platform. This system effectively combines low-cost PRP with a dual-network matrix composed of alginate (Alg) and sulfonated bacterial cellulose (SBC). The negatively charged surface of the Alg1SBC scaffold mimics the electrostatic characteristics of hepatic sinusoids, facilitating efficient PRP adsorption and sustained release of growth factors. Importantly, calcium ions not only crosslinked the scaffold to mimic liver-like mechanical stiffness but also activated PRP through a thrombin-independent mechanism, thereby promoting the controlled release of autologous growth factors. In mouse model of liver failure, the PRP-functionalized Alg1SBC scaffold improved primary hepatocyte engraftment, accelerated the formation of a functional hepatic niche, and prolonged survival. These findings represent a significant advance in scaffold-guided regenerative therapy for liver failure, underscoring the clinical potential of PRP-activated biomimetic systems in hepatology.

Effective healing of large bone defects is a clinical challenge. Extracellular vesicle (EV)-mediated cell-free therapy has great potential in bone defect repair; however, unmodified EVs generally exhibit limited osteogenic potential. Bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic cytokines reported to date. Here, we modified the EVs from BMP9-stimulated adipose-derived mesenchymal stem cells (iMAD), designated as B9-EVs. Subcutaneous injections of B9-EVs in immune-competent mice elicited no detectable host immune response. B9-EVs effectively induced in vitro osteogenic markers and promoted subcutaneous bone formation and cranial defect repair in vivo, similar to the direct use of recombinant adenovirus-mediated BMP9 overexpressing (AdR-B9) transduced iMAD cells. The miRNA-seq analysis of B9-EVs identified a distinct set of osteogenesis-related miRNAs. RNA-seq analysis revealed that osteogenesis-associated transcripts regulated in B9-EVs-stimulated MSCs were overlapping with but also distinct from those in AdR-B9-stimulated MSCs. Further bioinformatic analysis established an miRNA-mRNA network and revealed that the functionalized B9-EVs may regulate 10 miRNAs and 11 mRNA transcripts to induce osteogenesis through mechanisms that are unique and distinct from those associated with direct BMP9 stimulation. Collectively, given their cell-free and non-immunogenic nature, the functionalized osteogenic B9-EVs hold great potential for bone tissue engineering by providing effective osteogenic factors through EV-mediated paracrine signaling mechanisms.

Proteins are an effective platform for vaccine design by enabling multivalent antigen presentation and stabilizing antigen structures to enhance immunogenicity. This study investigates the molecular design and ability to position antigens on self-assembled protein nanocages (SAPNs) as a universal influenza vaccine, incorporating highly conserved nucleoprotein peptides (NP55-69 and NP147-158) as CD4⁺ and CD8⁺ T cell antigens alongside hemagglutinin stalk (HrHA) and matrix protein 2 ectodomain (4M2e). The SAPNs display HrHA and 4M2e on their external surface while embedding NP antigens internally. The engineered SAPNs feature a modular design, enabling precise antigen placement and enhanced accessibility through optimized linker length. This nanostructure elicited robust cellular and humoral immune responses in mice, including cross-reactive antibodies and antigen-specific T cell activation. These findings highlight the potential of SAPNs as a versatile platform for universal influenza vaccine development and the role that protein design plays in the spatial organization of self-assembled protein materials and its effect on biomedical function.

Porous biomaterials that integrate tunable biophysical and biochemical cues have been extensively studied for guiding cell behavior and harnessing the body's intrinsic regenerative potential. Aerogels, characterized by their ultralight structure, high porosity, and large surface area, have emerged as promising porous scaffolds for tissue engineering; however, their limited pore tunability may hinder efficient cell infiltration and functional tissue integration. To address this persistent limitation, we develop a new class of porous biomaterials called granular aerogel scaffolds (GAS), assembled from size-tunable gelatin methacryloyl (GelMA) microparticles, enabling the precise control of pore geometry and interconnected micron-scale void networks within the aerogels. GelMA hydrogel microparticles are jammed and photocrosslinked to yield granular hydrogel scaffolds (GHS), followed by supercritical carbon dioxide drying, yielding GAS with tunable pore microarchitecture and preserved structural integrity. Importantly, rehydrated GAS have comparable mechanical, rheological, and pore characteristics to GHS. In vitro analyses and in vivo subcutaneous implantation show that GAS are non-toxic and support progressively greater cell infiltration as the size of their microparticle building blocks increases. Further in vivo analyses using a hindlimb micropuncture surgery model show an increase in scaffold vascularization and vessel maturation with an increase in microparticle size. This work establishes a platform for engineering aerogels with precisely tuned cell-scale interconnected pores, enabling rapid cell infiltration, tissue integration, and vascularization. GAS may serve as versatile, shelf-ready biomaterials for tissue engineering and regenerative medicine.

Taxane-based chemotherapy and immunotherapy are standard treatments for advanced prostate cancer, yet their efficacy is often limited by drug resistance and an immunosuppressive, "cold" tumor microenvironment (TME). To address these challenges, we develop a reactive oxygen species (ROS)-responsive nanoparticle, PTX-Zn NP, for the co-delivery of paclitaxel (PTX) and zinc ions (Zn²⁺). Within tumor cells, elevated ROS triggers the release of PTX, promoting micronuclei formation and cytosolic double-stranded DNA exposure. Concurrently, Zn²⁺ amplifies cGAS-STING signaling by enhancing cGAS-DNA binding and inducing mitochondrial damage. In vitro, PTX-Zn NP suppressed tumor cell proliferation, generated ROS and micronuclei, and activated the STING pathway to promote dendritic cell maturation. In vivo, PTX-Zn NP preferentially accumulated in prostate tumors, inhibited tumor growth, and reprogrammed the "cold" TME toward a "hot" phenotype. When combined with anti-PD-L1 therapy, PTX-Zn NP significantly improved antitumor efficacy and promoted long-term immune memory. Overall, this dual-action approach provides a promising strategy to overcome both chemoresistance and immune evasion in advanced prostate cancer.