ACS Applied Bio Materials最新文献

Driven by the increasing need for the biofabrication of complex hydrogels, this work introduces a class of fish-porcine composite hydrogels that combine rapid, tunable photo-cross-linking with microparticle reinforcement for advanced 3D printing. Here, precross-linked porcine gelatin (methacrylated porcine gelatin, MPG) microparticles are incorporated into a methacrylated fish gelatin (MFG) matrix to produce robust yet easily processable hydrogels. Nuclear magnetic resonance (NMR) confirmed the degree of methacrylation, while scanning electron microscopy (SEM) revealed the hierarchical porosity vital for tissue integration. Detailed Mastersizer measurements characterized the size distributions of the MPG microparticles, and rheological tests demonstrated the composite hydrogels' strong shear-thinning behavior, an essential trait for extrusion-based and embedded 3D printing. Thermal (TGA, DSC) and mechanical (compression) analyses show that the microparticle-reinforced hydrogels achieve improved thermal stability, adjustable mass swelling ratio, and customizable compressive moduli. As a proof of concept, these composites are validated in digital light processing (DLP) printing of microfluidic constructs and as a support bath for embedded printing of complex geometries. This platform provides a unique synergy of easy UV cross-linkability, tunable mechanical features, and 3D printing versatility. This advancement underscores the potential of these materials as a foundational platform in tissue engineering, opening new avenues for creating complex, biocompatible structures with customizable properties.

An extensive amount of research has been focused on the development of state-of-the-art methodologies for drug administration. In this study, we have utilized density functional theory (DFT) for assessing the ability of a Twin monolayer of boron nitride and graphene, i.e., Twin-BN and Twin-Gr monolayer, as a carrier for delivering four anticancer drugs (ACDs) 5-fluorouracil (5-FU), gemcitabine (GC), cyclophosphamide (CP), and mercaptopurine (6-MP). Also, the properties of all drug molecules along with the Twin-BN and Twin-Gr and the complex of the ACD-Twin-BN/Gr monolayer were investigated to explore the usefulness of the Twin-BN and Twin-Gr monolayer as ACD carrier. The interaction between the monolayers and ACDs confirmed that the adsorption is feasible as the adsorption energy ranged from -0.41 eV to -0.95 eV in the case of Twin-BN, while it ranged from -0.43 eV to -0.61 eV in the case of Twin-Gr. Additionally, the change in the band gap of the Twin-BN and Twin-Gr monolayers after the adsorption of ACDs was considerable. We can conclude that among both monolayers, Twin-BN can be utilized as a highly effective carrier for delivering ACDs. Our findings showed that the monolayer Twin-BN could be explored as a drug transporter for highly efficient carrying of the considered ACDs.

Resilient hydrogels are of great interest in soft tissue applications, such as soft tissue engineering and wound healing, with their biomimetic mechanical and hydration properties. A critical aspect in designing hydrogels for healthcare is their functionalities to control the surrounding biological environments to optimize the healing process. Herein, we have created an elastomer-clay nanocomposite hydrogel system with biomimetic mechanical behavior and sustained drug delivery of bioactive components and malodorous diamine-controlling properties. These hydrogels were prepared by a combined approach of melt intercalation of poly(ethylene glycol) and montmorillonite clay, followed by in situ cross-linking with a branched poly(glycerol sebacate) prepolymer. The hydration, vapor transmission, and surface wettability of the hydrogels were readily controlled by varying the clay content. Their mechanical properties were also modulated to mimic the Young's moduli (ranging between 12.6 and 105.2 kPa), as well as good flexibility and stretchability of soft tissues. A porous scaffold with interconnected pore structures as well as full and instant shape recovery was fabricated from a selected nanocomposite to demonstrate its potential applications as soft tissue scaffolds and wound healing materials. Biodegradability and biocompatibility were tested in vitro, showing controllable degradation kinetics with clay and no evidence of cytotoxicity. With the high surface area and absorption capacity of the clay, sustained drug delivery of a proangiogenic agent of 17β-estradiol as a model drug and the ability to control the malodorous diamines were both achieved. This elastomer-clay nanocomposite hydrogel system with a three-dimensional interconnected porous scaffold architecture and controllable hydration, mechanical, and biodegradable properties, as well as good biocompatibility and the ability to control the biological chemical species of the surrounding environments, has great potential in soft tissue engineering and wound healing.

Both silicon (Si) and magnesium (Mg) ions play essential roles in bone health. However, the precise mechanisms by which these two ions enhance osteogenic differentiation remain to be fully elucidated. Herein, a Si-Mg dual-ion system was designed to investigate the effects of Si and Mg ions on the cytological behavior of mouse bone marrow mesenchymal stem cells (mBMSCs). The molecular mechanism of the Si-Mg dual-ion system regulating osteogenic differentiation of mBMSCs was investigated by transcriptome sequencing technology. In the single-ion system, the Si group with concentrations of 1.5 and 0.75 mM exhibited good combined effects (cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation gene expression (Runx2, OPN, and Col-I)) of mBMSCs. The Mg group with concentrations of 5 and 2.5 mM showed better combined effects (cell proliferation, ALP activity, and osteogenic differentiation gene expression) of mBMSCs. In the dual-ion system, the silicon (0.75 mM)-magnesium (2.5 mM) experimental group significantly enhanced the proliferation, ALP activity, and osteogenesis-related gene expression (Runx2, OPN, and Col-I) of mBMSCs. The analysis of transcriptome sequencing results showed that Mg ions had a certain pro-stem cell osteogenic differentiation regulatory effect. Si ions had a stronger regulation on osteogenic differentiation than the Mg ions. The regulation of osteogenic differentiation by Si-Mg dual ions was synergistically enhanced compared to that of a single ion. In addition, the transforming growth factor beta (TGF-β) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway were involved in mediating the pro-stem cell osteogenic differentiation by Si-Mg dual ions. This study sheds light on investigating the molecular mechanism of dual-ion regulation of the osteogenic differentiation of mBMSCs and enriches the theory of ion-regulating osteogenic differentiation.

Bone defects arising from trauma, disease, or surgical intervention represent significant challenges. Developing effective bone tissue engineering strategies to address these issues and promote repair is crucial. β-Tricalcium phosphate (β-TCP) has emerged as a promising synthetic graft due to its porous, degradable structure and excellent biocompatibility. However, the lack of biological cues in β-TCP limits its functionality, requiring different surface modification strategies. Bone morphogenetic protein-2 mimetic peptide (BMP; NSVNSKIPKACCVPTELSAI) and collagen mimetic peptide (CMP; GTPGPQGIAGQRGVV) have a known significant therapeutic potential due to their ability to enhance cell attachment and osteogenic differentiation. Herein, a peptide functionalization strategy for β-TCP scaffolds was introduced. Briefly, β-TCP was treated with cold atmospheric plasma (CAP) to create functional hydroxyl groups on the surface of the β-TCP. Subsequently, peptides were conjugated by using a three-step method: (1) silanization with APTES, (2) EDC activation, and (3) peptide conjugation. The successful surface modification with CAP and peptide conjugation was confirmed via XRD, FTIR, and Raman analysis. Furthermore, the effects of BMP and CMP peptides on osteogenic differentiation after CAP treatment were investigated in human mesenchymal stem cells (hMSCs). Both β-TCP/BMP and β-TCP/CMP scaffolds demonstrated excellent biocompatibility with hMSCs, enhancing cell proliferation and promoting osteogenic differentiation. Remarkably, β-TCP/CMP showed better results in terms of proliferation and differentiation compared with β-TCP/BMP. These findings highlight the clinical potential of peptide-functionalized β-TCP scaffolds for bone tissue engineering while also providing a promising methodology for β-TCP functionalization.

The development of simple and versatile approaches for the fabrication of DNA-based composite nanomaterials, endowed with defined morphologies and specific functionalities, is of paramount importance for various applications. Herein, we report a simple approach for the synthesis of multifunctional copper-DNA nanoflowers (Cu-DNF) that exclusively consist of rolling circle polymerized nanoflowers (DNF) and in situ synthesized concatemeric fluorescence copper nanoparticles. Through meticulous regulation of the assembly process, it is possible to generate Cu-DNF with precise sizes and stable fluorescence properties. The obtained Cu-DNF possesses robust biostability to resist degradation by nuclease, presumably resulting from the dense structure of the Cu-DNF. The Cu-DNF were also encoded with polyvalent tandem CD63 aptamer sequences, which enhanced their binding affinity and internalization efficiency into tumor cells. We demonstrate that the multifunctional Cu-DNF can efficiently internalize tumor cells for tracking and imaging analysis of intracellular microRNA. This approach may be beneficial for creating multifunctional DNA-based composite nanomaterials for various technological applications.

A wide array of artificial O₂ carriers based on hemoglobin (Hb) has been developed to serve as substitutes for red blood cells (RBCs). Nevertheless, the prevention of heme-iron oxidation within Hb remains a critical challenge. In this study, we synthesized a nanoparticle O₂ carrier comprising a polymerized stromal-free Hb (SFHb) core covered with a human serum albumin shell, designated as SFHbNP. With an optimized particle size of approximately 30 nm, SFHbNPs are engineered to evade uptake by the reticuloendothelial system in various organs. We characterized the physicochemical properties and biochemical functions of SFHbNPs, demonstrating that the incorporation of trace amounts of the antioxidant enzyme catalase within the core effectively suppresses Hb autoxidation. The SFHbNP solution exhibited excellent compatibility with human blood and demonstrated no cytotoxicity toward human endothelial cells. Moreover, its extended circulatory retention enabled preclinical evaluation in animal models. In a rat model of 50% hemorrhagic shock, administration of SFHbNP solution achieved full resuscitation, as evidenced by the restoration of circulatory parameters. Serum biochemistry tests and histopathological analyses of major organs indicated no adverse effects. Comprehensive in vitro and in vivo studies confirm the safety and potential efficacy of SFHbNPs as a promising RBC alternative in transfusion medicine.