ACS Biomaterials Science & Engineering最新文献

IgA nephropathy (IgAN) is a primary glomerulonephritis mediated by autoimmunity, characterized by an abnormal increase and the deposition of IgA in the glomeruli. In recent years, most studies have emphasized the crucial role of the gut–kidney axis in the pathogenesis of IgA nephropathy, and the ileal Peyer patches in the intestinal mucosal immune system are the main site for IgA production. Therefore, in this study, hydroxychloroquine (HCQ) and dexamethasone (DXM) were used as model drugs, and yeast cell wall (YCW)-coated oleic acid-grafted chitosan (CSO) was used as a carrier to construct a yeast cell wall oral drug delivery system HCQ/DXM@CSO@YCW. This delivery system achieves ileal targeted delivery through the yeast cell wall (YCW), reduces IgA production, and synergistically regulates the inflammatory pathological environment. The delivery system had good gastrointestinal stability and biocompatibility. In vitro cell experiments had shown the targeted uptake ability of dendritic cells and macrophages, and in vitro intestinal experiments showed that the YCW has ileal targeting properties. In vivo pharmacodynamic experiments showed that the HCQ/DXM@CSO@YCW delivery system could significantly reduce the serum IgA levels and IgA deposition in the renal tissue of IgAN mice, as well as the levels of IL-6, TNF-α, and TGF-β in the renal tissue, improving the pathological morphology of the renal tissue. Therefore, the DXM/HCQ@CSO@YCW oral administration system provided a new intestinal targeted delivery platform for intestinal mucosal immunotherapy in IgA nephropathy.

The increasing prevalence of multidrug-resistant bacteria is a significant global health threat. In contrast to conventional antibiotic treatments, photodynamic therapy (PDT) offers a promising alternative by reducing the bacterial adaptability to antibiotics and bactericides. However, traditional photosensitizers encounter poor antimicrobial efficacy due to poor hydrophilicity of photosensitizers, short lifespan, narrow diffusion radius of reactive oxygen species (ROS), and the risk of exacerbating inflammation. In this study, we report a bacterial-targeting supramolecular nanophotosensitizer for combating multidrug resistant bacteria. The nanophotosensitizer, formed through host–guest interactions and self-assembly of tetra-cyclodextrin-modified silver porphyrin (AgTPP-CD₄), adamantyl-modified phenylboronic acid (Ad-PBA), and curcumin (Cur), can effectively target and kill methicillin-resistant Staphylococcus aureus (MRSA). Moreover, it reduces inflammation and promotes wound healing in MRSA-infected wounds without inducing drug resistance. The combination of supramolecular chemistry and targeted PDT offers a promising strategy for combating multidrug-resistant bacterial infections.

There exists a significant correlation between the microstructural evolution and the mechanical properties of fibers during repeated loading and unloading cycles. Nevertheless, the influence of deformation and the duration of intervals on the structural and tensile behavior of spider silk after repeated stretching at a given strain value has been rarely reported, with the exception of studies focusing on the major ampullate gland silk (Mas) of the spider. In order to investigate the effects of repeated stretching on the structural and mechanical behavior of spider tubular gland silk (Tus), the tensile properties and the changes in semiquantitative protein secondary structure of Argiope bruennichi Tus during loading–unloading cycles were characterized. The results indicate that the typical tensile behavior curves of Tus were irreversibly modified to resemble those of Mas, demonstrating a clear yield region accompanied by a necking phenomenon. The Tus displays remarkable characteristics of repeated stretching and mechanical memory, and it is capable of reproducing the tensile behavior of fibers subjected to one stretch, independent from its previous loading history. The above phenomenon may be caused by repeated stretching leading to the damage and reconstruction of protein structures, including an increase in α-helix content and the rearrangement of spider-silk proteins, enabling them to reproduce their mechanical behavior. These findings may provide valuable insights for the biomimetic design of novel fiber materials, such as the spider silk gut, through the artificial stretching of spider silk glands.

Pathological fibrosis is a chronic disease, characterized by excessive extracellular matrix deposition, that remains a significant global health challenge. Despite its prevalence, current antifibrotic therapies are limited due to the complex interplay and signaling of profibrotic macrophages and fibroblast cells that underlies fibrotic tissue microenvironments. This study investigates a novel approach to combat fibrosis, harnessing the antifibrotic properties of the endogenous metabolite itaconate (IA) to target the pathological activation of the macrophage-fibroblast axis in fibrotic disease. To achieve therapeutic delivery relevant to the chronic nature of fibrotic conditions, we incorporated IA into the backbone of biodegradable polyester polymers, poly(dodecyl itaconate) (poly[IA-DoD]), capable of long-term localized release of IA. Degradation characterization of poly(IA-DoD) revealed that IA, as well as water-soluble IA-containing oligomeric groups, is released in a sustained manner. Treatment of murine bone marrow-derived macrophages and human dermal fibroblasts demonstrated that the degradation products of poly(IA-DoD) effectively modulated profibrotic behavior. Macrophages exposed to the degradation products exhibited reduced profibrotic responses, while fibroblasts showed decreased proliferation and myofibroblast α-smooth muscle actin expression. These findings suggest that poly(IA-DoD) has the potential to disrupt the fibrotic cycle by targeting key cellular players. This polymer-based delivery system offers a promising strategy for the treatment of fibrotic diseases.

Dimethylcurcumin (ASC-J9) is an organic active pharmaceutical ingredient with anti-inflammatory, antioxidant, and antitumor effects. However, its application has been significantly hindered by poor solubility in aqueous solutions, a short in vivo half-life, low bioavailability after oral administration, and limited accumulation and absorption in target areas. Nano-drug delivery systems can serve as drug carriers to enhance drug delivery, addressing these challenges with improved efficacy and reduced adverse effects. In this study, a microfluidic swirl mixer is used to prepare silk fibroin composite nanoparticles containing ASC-J9 and copper sulfate (CuS), and the effects of different process parameters on silk fibroin nanoparticles (SNPs) were explored and optimized. The synthesized composite ASC-J9-CuS@SNPs exhibited a mean particle diameter of 180 ± 10 nm and PDI of 0.20 ± 0.03. Two-dimensional/three-dimensional (2D/3D) cell experiments showed that the composite nanomaterials have excellent biocompatibility and antitumor activity with a noticeable cancer cell specificity. In vivo experiments showed that ASC-J9-CuS@SNPs effectively controlled tumor growth without causing damage to blood cells and vital organs. Both in vitro and in vivo experiments demonstrated that the anticancer effect was enhanced by photo thermotherapy. The current study provides a promising strategy for using silk fibroin as nanocarriers for breast cancer therapy.

The impaired healing of alveolar bone defects in diabetic patients has attracted considerable attention, with Mogroside V (MV) emerging as a promising candidate due to its demonstrated antioxidation, hypoglycemic, and anti-inflammatory properties in patients with diabetes mellitus. To address the limitations of oral MV administration, such as low bioavailability, rapid metabolism, and a short half-life, we developed a nanofiber membrane utilizing electrospinning technology for topical application by preparing membranes using MV, chitosan (CS), nanohydroxyapatite (HA), and poly(vinyl alcohol) (PVA) as raw materials to prolong the effect of MV and enhance bone regeneration in diabetic patients. The MV/HA/PVA/CS exhibited a good fiber diameter, prolonged drug release, and suitable degradation time, along with other favorable properties. In vitro experiments revealed its excellent biocompatibility, effectiveness in promoting osteogenesis, upregulation of osteogenic and anti-inflammatory genes, and concurrent downregulation of pro-inflammatory genes. In vivo evaluations further confirmed its ability to effectively modulate the diabetic microenvironment, reduce bone damage, and facilitate anti-inflammatory effects and alveolar bone regeneration in diabetics. These findings suggest that a nanofiber membrane with sustained release of MV may serve as a promising biomaterial, providing new insights into improving the healing of diabetic alveolar bone defects.

Adding metal ions is a promising strategy to enhance the biological performance of titanium implants. In this study, we aimed to explore the effects of yttrium on the osseointegration of titanium implants. First, a series of yttrium-doped titanium surfaces were fabricated via microarc oxidation (MAO) by incorporating yttrium acetate into the electrolyte, and then the surface characteristics of different substrates were evaluated. Subsequently, the cellular behaviors of different coatings were assessed, and the osteointegration effects were examined using a rat model. Finally, high-throughput sequencing was employed to elucidate the underlying mechanisms of the yttrium-doped MAO coatings. As the results indicated, the proportion of yttrium in the coatings increased as the concentration of yttrium acetate improved. Surface characterization revealed that the yttrium-doped MAO coatings exhibited a homogeneous porous morphology, with comparable roughness and wettability to those of the undoped MAO coating, while the morphology became inconsistent when the yttrium acetate concentration reached 30 mM. The in vitro assays demonstrated that the addition of yttrium notably improved the cell adhesion, spreading, proliferation, and osteogenic differentiation of MAO coatings when doped with a low proportion, accompanied by enhanced osseointegration according to the in vivo experiments. Further exploration revealed a significant enrichment of osseointegration-related signaling factors and the activation of BMP/Smad signaling in the effects of yttrium-doped titanium coatings, which was attributed to the excessive accumulation of phosphorylated Smad1/5/9 in the nucleus. In summary, our work demonstrates that the use of MAO coatings doped with a low proportion of yttrium can enhance the osseointegration of titanium implants, providing an efficient strategy to optimize titanium implant performance.

Therapeutic protein delivery has ushered in a promising new generation of disease treatment, garnering more recognition for its clinical potential than ever. However, proteins’ limited stability, extremely short average half-lives, and evidenced toxicity following systemic delivery continue to undercut their efficacy. Biomaterial-based protein delivery, however, demonstrates the potential to overcome these obstacles. To this end, we have developed a heparinized alginate and collagen hydrogel for the local, sustained delivery of therapeutic proteins. In an effort to match this ubiquitous application of protein delivery to various disease states and target tissues with sufficient versatility, we identified three distinct delivery modes as design targets. A shear-thinning, low-viscosity injectable for minimal tissue damage, a higher-viscosity gel plug for subcutaneous injection, and a submillimeter-thickness film for solid-form implantation were optimized and characterized in this work. In vitro assessments confirmed feasible injection control, mechanical stability for up to 6 h of unsubmerged storage, and isotropic early collagen fibril assembly. Release kinetics were assessed both in vitro and in vivo, demonstrating up to 14 days of functional vascular endothelial growth factor delivery. Rodent models of pulmonary hypertension, subcutaneous injection, and myocardial infarction, three promising applications of protein therapeutics, were used to assess the feasible delivery and biocompatibility of the injectable gel, gel plug, and film, respectively. Histological evaluation of the delivered materials and surrounding tissue showed high biocompatibility with cell and blood vessel infiltration, remodeling, and integration with the host tissue. Our successful customization of the biomaterial to heterogeneous delivery modes demonstrates its versatile capacity for the local, sustained delivery of therapeutic proteins for a diverse array of regenerative medicine applications.

Although the Masquelet-induced membrane technique (MIMT) is now employed worldwide for bone defects, it often needs to be repeated and autogenous bone graft. This study aims to investigate the theoretical feasibility of replacing PMMA (poly(methyl methacrylate)) bone cement with PLLA (poly-l-lactic acid)/β -TCP (beta-tricalcium phosphate)/CS (calcium sulfate) scaffold for single-stage bone defect reconstruction, which evoke the induced membrane (IM) formation in the early stage and directly acts as the implantation in the second stage to reconstruct the bone defect. We constructed a corn-like PLLA/β -TCP/CS scaffold by the fused deposition 3D printing method. The characterizations of the scaffolds were investigated systematically. The P/T15/S15 scaffolds (the PLLA/β -TCP/CS scaffold with a 15% mass fraction of β-TCP and 15% mass fraction of CS) were filled into the large-segmental radius bone defects of white rabbits to evoke the formation of IMs. HE (hematoxylin–eosin) and VG (van gieson) staining, along with immunofluorescent staining, were performed to analyze the architecture and cellularity, the expression of BMP-2 (bone morphogenetic protein-2), VEGF (vascular endothelial growth factor), and TGF-β1 (transforming growth factor-β1) was evaluated by IHC (immunohistochemistry) and WB (western-blot) respectively, the ALP (alkaline phosphatase) and ARS (alizarin red S) staining was applied to assess the osteogenic potential. The corn-like PLLA/β-TCP/CS scaffolds with excellent physicochemical properties are successfully constructed using the fused deposition 3D printing technique. The HE and VG staining, along with immunofluorescent staining, suggested that the P/T15/S15 scaffold effectively mediated the formation of IM after 6 weeks of placement. A significant presence of M2 macrophages was observed in IM. The results of IHC and WB demonstrated that the IMs derived from the P/T15/S15 scaffolds exhibited elevated levels of VEGF, BMP-2, and TGF-β1, all of which promote the osteogenic differentiation of BMSCs. The results of cellular immunofluorescence, flow cytometry, and WB indicate that P/T15/S15 regulates the phenotypic polarization of M0 macrophages toward the M2 phenotype via the PI3K/AKT/β-Catenin pathway. These findings suggest that the biodegradable PLLA/β-TCP/CS scaffold may serve as a viable alternative to PMMA bone cement for single-stage bone defect reconstruction, owing to its unique ability to stimulate IM formation and promote the polarization of macrophages toward the M2 phenotype. This work presents innovative materials and strategies for the management of bone defects.

The fluorescent silk produced by feeding silkworms with traditional fluorescent dyes is limited in functionality and suffers from fluorescence quenching, rendering it unsuitable for long-term stable performance as a medical implant material in the human body. This work introduces an innovative strategy to develop a novel multifunctional fluorescent silk composite by incorporating quercetin (QR), a naturally occurring molecule with aggregation-induced emission (AIE) characteristics, into the diet of silkworms. Silk derived from QR-fed silkworms presents significant enhancements in fluorescence, antioxidant, and mechanical properties, with the QR-2.5% group presenting the best overall performance. The resulting silk exhibits superstrong blue fluorescence when exposed to 405 nm laser light, with a breaking strength of 4.26 ± 0.42 cN/D and a breaking energy of 5.96 ± 1.32 cN/cm, improvements of 15.76% and 18.25%, respectively, in comparison with regular silk. Fourier transform infrared spectroscopy (FTIR) analysis indicates that QR induces a structural transformation of fibroin protein from α-helix and random coil to β-sheet configuration, thereby increasing silk crystallinity. Additionally, compared with regular silk, the antioxidant properties of both sericin and silk fibroin increased by 88.66% and 17.25%, respectively. At the same time, this multifunctional silk has excellent biocompatibility and strong cell adhesion. The high-strength, uniformly luminescent silk developed in this study has outstanding antioxidant and mechanical properties. It effectively avoids the fluorescence quenching issue common in traditional fluorescent silk materials and introduces new functionalities. This advancement is significant for increasing the utility of functionally modified silk.