Biomaterials Science最新文献

Polymer conjugation is a common strategy to improve the pharmacokinetics of aptamers, yet its effects on aptamer properties are incompletely understood. Poly(ethylene glycol) (PEG) is the most widely used polymer for this purpose, but concerns about anti-PEG immune responses have prompted interest in alternative polymers. We previously reported that conjugation with the zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) significantly prolongs the circulation time of a DNA aptamer while avoiding anti-PEG antibody recognition. In this study, we evaluated the physicochemical and functional consequences of PMPC conjugation of aptamers. Biophysical analyses suggested that the secondary structure and target-binding affinity of the aptamer were preserved, while functional consequences upon PMPC conjugation varied with the targets. The activity of a membrane receptor-targeting aptamer partially decreased, likely due to spatial constraints around the cell membrane, while RB005, targeting soluble activated coagulation factor IX, retained its full activity. In addition, PMPC conjugation significantly prolonged the in vivo plasma retention of RB005. By elucidating the effects of PMPC on aptamer properties and introducing another example that further supports the general applicability of PMPC conjugation in enhancing aptamer pharmacokinetics, these findings support PMPC as a promising alternative to PEG.

Bone powder-laden hydrogel scaffold is emerging as a promising bone graft material to offer solutions for bone defect repair in bone tissue engineering. Numerous hydrogel composite scaffolds loaded with xenobiotic bone powder or alloplast bone powder have been developed for preclinical experiments. In vitro experiments conducted on osteogenesis-related cells and in vivo studies using bone defect animal models have demonstrated that bone powder-laden hydrogel scaffolds exhibit favorable physicochemical properties, enhance the osteogenic behavior of osteogenesis-related cells, and improve the quality and efficiency of bone defect repair in animals. Bone powder-laden hydrogel scaffold can maximize the performance of individual components. However, this material has several limitations and has not yet been approved for clinical trials. Therefore, recent research has explored related products with superior properties, enhancing the mechanical, chemical, and biological characteristics of bone powder-laden hydrogel scaffolds, and proposed various strategies for improvement. This review summarizes the preparation procedures, therapeutic applications and possible improvements of various types of bone powder-laden hydrogel scaffolds.

Currently, single-target therapy and difficulty in brain drug delivery gravely impede the treatment of Alzheimer's disease (AD). The promising development of microRNA-124-3p (miR-124-3p) serves as a possibility for multiple therapeutic approaches for AD. However, the effective delivery of miR-124-3p to AD-affected brain regions remains a major challenge, primarily due to the blood-brain barrier (BBB) and the inherent instability of therapeutic miR-124-3p. Herein, we engineered miR-124-3p-enriched microglial exosomes (Exo-124-3p) as a biomimetic nanomedicine for the multifunctional treatment of AD. Exo-124-3p can traverse the BBB and facilitate activated-microglia targeting. Subsequently, the on-demand release of miR-124-3p from Exo-124-3p decreased the aggregation of β-amyloid (Aβ) plaques, attenuated the activation of microglia/astrocytes, and exhibited a valuable neuroprotective effect, thereby remolding the AD focal microenvironment. Notably, the in vivo results demonstrated that Exo-124-3p significantly improved the cognitive function in an AD mouse model. Mechanistically, it was elucidated that Exo-124-3p can bind to the 3'UTR region of MEKK3, ultimately inhibiting the MEKK3/NF-κB signaling pathway, thereby ameliorating AD neuroinflammation. Consequently, this study not only provides a promising therapeutic approach for AD combinational therapy, but also advances the development of miRNA delivery in other brain diseases.

Gelatin dissolvable microneedle (DMN) patches offer a promising, painless, and rapid transdermal delivery platform. However, conventional DMNs with <5% w/v gelatin exhibit poor mechanical strength and storage stability of biomolecules, while higher concentrations (>5% w/v) hinder dissolvability due to gelation. To address this, we introduced a tailored number of carboxylic groups into the gelatin backbone, generating Modified Gelatin (MG) with improved solubility and reduced viscosity by limiting intra- and intermolecular interactions. MG-DMNs fabricated from MG at a concentration of 10%-20% w/v and ≥5% w/v stabilizing molecules (e.g., trehalose) exhibited rapid dissolution (5 minutes), high mechanical strength (>95 N per patch), and excellent storage stability. Notably, MG-DMNs retained >80% of platelet-rich plasma (PRP) activity after one month of storage at 4 °C and 25 °C, and ∼60% at 40 °C under 75% relative humidity, as confirmed through an in vitro bioassay, an in ovo CAM assay, and in vivo diabetic wound healing studies. MG-DMNs enable the cold-chain-free and stable delivery of biomolecules for biomedical applications.

Diabetic wound healing has long been plagued by a series of complex problems caused by the pathological environment of high glucose, such as ischemia, hypoxia, and inflammatory responses. In order to solve this dilemma, we developed a new gel preparation with both green natural characteristics and excellent biological activity, aiming to provide an efficient and safe solution for diabetic wound healing. The gel uses microalgae as the core carrier, and it also plays an important role as an oxygen supply source. Through covalent bonding, the functional component concanavalin A and PEG-modified gold nanoparticles (PEG-AuNPs) were efficiently loaded on the polymer, which ensured the stable existence and controlled release of the components. Subsequently, the composite system was incorporated into the pre-gel fluid of the photocrosslinked methacryloylated gelatin to obtain our designed gel composite. On the one hand, the microalgae present in the material can continuously produce oxygen driven by light, effectively improve the local hypoxic microenvironment of the wound, and provide sufficient oxygen for cell proliferation and tissue repair. On the other hand, concanavalin A can specifically bind to glucose, and then cooperate with AuNPs with glucose oxidase activity to exert an efficient local hypoglycemic effect, thereby alleviating the adverse effects of high glucose on healing from the root. Through systematic experimental verification, this study confirmed the application prospects of this biocomposite material with multiple pro-healing properties in the field of diabetic wound management.

Osteoarthritis, as one of the major disabling diseases in the elderly, has a long-term impact on patients' quality of life and brings heavy medical and social burden. The pathogenesis of osteoarthritis is still unclear, and the main pathological changes include chondrocyte death and osteochondral damage. Therefore, how to solve the cartilage damage caused by osteoarthritis has become the key and difficult point in the clinical treatment of osteoarthritis. Bone marrow mesenchymal stem cells (MSCs) have the potential for self-renewal and multidirectional differentiation, and their engineering has been a hot research topic for the treatment of cartilage damage in recent years. In this study, an injectable hydrogel with stable and continuous release of growth factors was successfully prepared by modifying bone marrow mesenchymal stem cells to overexpress fibroblast growth factor-2 (FGF-2) and piggybacking on a decellularized extracellular matrix (dECM) hydrogel for the repair of cartilage injury in osteoarthritis. This hydrogel demonstrated excellent biocompatibility both in vitro and in vivo. In 3D cell culture, BMSCs in the dECM hydrogel survived, proliferated, and produced abundant cartilage-specific extracellular matrix and growth factors, promoting BMSC differentiation into hyaline chondrocytes. In vitro and in vivo experiments, along with RNA-seq analysis, showed that engineered BMSCs loaded onto the dECM hydrogel could inhibit chondrocyte apoptosis and boost BMSC differentiation. In summary, dECM hydrogels carrying FGF-2 overexpressing bone marrow mesenchymal stem cells have great prospects in accelerating osteochondral defect repair and delaying the progression of osteoarthritis.

Post-central nervous system injury, the endogenous repair and mobilization of neural stem cells are insufficient, necessitating the reliance on exogenous cell transplantation as the predominant repair and replacement strategy. The behavior and differentiation fate of induced pluripotent stem cells (iPSCs) are highly susceptible to external stimuli, including the cell culture matrix and physical electromagnetic signals. In this study, we innovatively utilize magnetic graphene oxide composite nanoparticles to regulate the proliferation and neural lineage differentiation of induced pluripotent stem cell-derived neural progenitor cells (iPSC-derived hNPCs). Our results reveal that a specific concentration of magnetic graphene oxide effectively maintains stemness properties, promotes cell proliferation, and preferentially directs differentiation toward neuronal lineages under induced differentiation conditions. Additionally, this treatment upregulated the expression of synaptic-related proteins while concurrently reducing the astrocytic differentiation ratio. These findings provide a novel materials-based strategy for optimizing hNPCs in vitro culture and directed differentiation systems.

Vaccines have been crucial to dramatic improvements in global health in recent decades, yet next-generation vaccine technologies remain out of reach for much of the world. In particular, there are two overarching global needs: (i) develop vaccines eliciting more potent and durable immune responses, especially to reduce incidence of highly communicable diseases, and (ii) enable simple and cost-efficient formulation to maximize global access. Here, we develop an injectable hydrogel depot technology prepared through physical mixing of commercially available, generally recognized as safe (GRAS) polymers that can be formulated with subunit vaccine components to improve immune responses compared to standard vaccine formulations. We demonstrate that these hydrogels are shear-thinning and rapidly self-healing, enabling facile administration via injection, and they exhibit high yield stresses required for robust in vivo depot formation post-injection. These rheological properties prolong release of subunit vaccine cargo over a period of weeks, both in vitro and in vivo, and synchronize release kinetics across physicochemically distinct vaccine components (antigens and adjuvants). When used for formulation of subunit vaccines against wild-type SARS-CoV-2 and H5N1 influenza, these hydrogels enhance potency and durability of immune responses. This vaccine formulation technology can improve protection against current and potential future pandemic pathogens.

Nanostructured surfaces are increasingly used for cell applications due to their enhanced interactions with numerous cell types; yet, their effects on tissues remain unexplored. To address this limitation, we designed vertical silicon nanopillar (Si-NP) arrays with high density, high aspect ratio and submicrometer diameter, as an optimized geometry based on previous cell-nanostructure studies. Using state-of-the-art in vitro and ex vivo assays, we examined adhesion and biocompatibility of biological samples of different origin and level of complexity -human epithelial-like cell lines, Drosophila imaginal discs and patient-derived lung cancer biopsies-laid on Si-NP arrays or unpatterned flat Si surfaces. Our results demonstrated that Si-NP arrays significantly improved cell and tissue adhesion while preventing oxidative damage and early apoptosis. Consistently, focused ion beam-scanning electron microscopy imaging of cells and tissues showed extended horizontal protrusions and limited vertical wrapping around Si-NP, revealing enhanced cell-NP interactions without cell/tissue penetration. In contrast, flat Si surfaces showed poor adhesion, increased apoptosis, and failed to support tumor biopsy attachment. Interaction with Si-NP arrays upregulated reactive oxygen species (ROS), yet mitochondria-associated ROS remained unchanged, and consequently apoptosis was not induced, indicating that the increased ROS arose from non-mitochondrial compartments and did not compromise viability. Notably, Si-NP arrays matched or outperformed biological responses on tissue culture plastic and Transwell-based assays, which are common in vitro and ex vivo substrates, respectively. These findings provide the first demonstration of the biological suitability of Si-NP arrays for tissue applications in research and clinical translation.

Ovarian cancer (OC) is one of the most fatal malignant tumors of the female reproductive system, and its high recurrence rate in advanced stages and drug resistance severely limit the efficacy of current treatment methods. The molecular mechanisms of drug resistance are complex and remain incompletely understood. Previous studies have attempted to enhance treatment sensitivity by co-delivering antitumor drugs with inhibitors of drug resistance-associated factors. However, these approaches often suffer from inadequate therapeutic efficacy and poor precision due to the inability to precisely control the sequential release of the two agents. To address this, this study designed and constructed a core-shell hydrogel microsphere (MSs) system with both sequential release and magnetothermal synergy functions to effectively intervene in drug-resistant OC. In this system, the shell layer is loaded with the DYRK1B inhibitor AZ191, which is released preferentially to disrupt drug-resistant signaling pathways and sensitize tumor cells. Subsequently, the core layer releases cisplatin to achieve sustained killing of tumor cells. In addition, magnetic nanoparticles embedded in the core can be heated to 42-46 °C under an alternating magnetic field, inducing thermosensitive apoptosis and enhancing cisplatin efficacy. This approach holds promise as a non-invasive alternative to traditional hyperthermic intraperitoneal chemotherapy (HIPEC). In vitro drug release experiments demonstrated that AZ191 exhibited rapid release within the first three hours with a cumulative release of approximately 26%, whereas cisplatin showed minimal early release (∼5%) followed by a markedly accelerated release. In vitro antitumor studies confirmed that the combined chemo-hyperthermia treatment using the core-shell MSs produced the most effective inhibitory effect on drug-resistant OC cells, reducing cell viability to 21% after 48 h, significantly outperforming either chemotherapy or hyperthermia alone. This strategy enables a "resistance-reversal first, precision-killing later" treatment model, offering a novel and effective solution for the treatment of drug-resistant OC.