Journal of biomedical materials research. Part B, Applied biomaterials最新文献

Failures in oral implant installation may be associated with elevated concentrations of matrix metalloproteinases (MMPs). The overexpression of these enzymes leads to extensive extracellular matrix degradation, delaying or impairing tissue repair. Moreover, their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are often insufficient to counteract pathologically elevated MMP levels. To address this, various MMP-regulating strategies have been explored, including the use of flavonoids such as naringenin (NA), a citrus-derived compound with promising anti-inflammatory effects and MMP downregulation. Additionally, surface modifications of titanium (Ti) implants can enhance tissue response and improve osseointegration. This study aimed to characterize and evaluate the effects of Ti surface modification through alkali treatment and NA-laden gelatin methacryloyl (GelMA) coating on osteoblast (Ob) functions related to peri-implant repair in vitro. Ti discs were alkalinized using 5 M sodium hydroxide (NaOH) at 60°C for 24 h. GelMA hydrogel (15% w/v) containing 0% (control) or 1% NA (w/w) was prepared and applied as a coating. The coatings were characterized for morphology, swelling, degradation, and NA release profile. SAOS-2 osteoblasts (HTB-85) were then cultured on the coated discs, and cell adhesion, viability, and synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed. Data were analyzed by one- or two-way ANOVA and Student's t-test/post hoc tests (α = 0.05). Scanning electron microscopy confirmed successful coating, with the GelMA+NA 1% group showing a more uniform and porous surface compared to GelMA alone. Both formulations displayed similar swelling capacity and degradation profiles over 21 days (p > 0.05). NA release was sustained for 14 days, peaking at 15 h. Cell viability and adhesion were comparable between groups (p > 0.05). Osteoblasts cultured on GelMA and exposed to the inflammatory stimulus tumor necrosis factor-alpha (TNF-α) showed increased synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2. However, cells cultured on GelMA+NA 1% exhibited significantly reduced MMP-2 and MMP-9 levels compared to GelMA under TNF-α stimulation (p < 0.05), with no significant changes in TIMP-1 or TIMP-2. In summary, Ti surface modification through alkali treatment followed by GelMA/NA coating was cytocompatible, showed controlled degradability, sustained NA release, and downregulated MMP synthesis in osteoblasts. These results suggest its potential as a promising strategy to modulate MMPs, which may help mitigate excessive matrix degradation and favor peri-implant tissue repair.

Bone tissue exhibits inherent bioelectrical properties, and electrical stimulation (ES) has been demonstrated to effectively accelerate bone healing. However, insufficient attention has been devoted to investigating biocomposite materials that synergize with electrostimulation for bone defect repair. In this study, a composite of strontium-doped hydroxyapatite and chitosan (Sr-HA@CS) was synthesized and demonstrated to promote bone regeneration. Under combined ES, the Sr-HA@CS hydrogel not only exhibited excellent injectability, biocompatibility, and osteoinductivity, but also significantly upregulated osteogenesis-related genes and accelerated the osteogenic process, as revealed by RNA sequencing analysis. This synergistic effect further promoted intracellular calcium enrichment and enhanced bone regeneration in vivo. Therefore, the development of the Sr-HA@CS composite combined with ES therapy holds promise for accelerating bone repair and represents an important area of research.

This study investigates the structural, morphological, hydrodynamic, colloidal stability, anticancer, antibacterial, antioxidant, and hemolytic properties of Cu and Mn doped ZnS nanosheets (NSs). XRD examination indicated that the produced NSs exhibit high purity with a cubic structure. The average crystallite size was determined to be 1.66 nm for ZCMn1, 1.60 nm for ZCMn2, 1.26 nm for ZCMn3, and 1.39 nm for ZCMn4 NSs (ZnS = ZCMn1; Zn_0.98Cu_0.02S = ZCMn2; Zn_0.97Mn_0.01Cu_0.02S = ZCMn3; Zn_0.96Mn_0.02Cu_0.02S = ZCMn4). TEM analysis showed that the synthesized NSs exhibit a crumpled nanosheet morphology with agglomerated particles. The ZCMn4 NSs displayed the smallest hydrodynamic size and the best colloidal stability. The ZCMn4 NSs also demonstrated superior antibacterial efficacy, with zones of inhibition (ZOI) measuring 14mm, 14 mm, 17 mm, 16 mm, and 13 mm for S. aureus, E. faecalis, P. aeruginosa, E. coli, and C. albicans, respectively. Antioxidant and hemolytic activities were also evaluated, further highlighting the multifunctionality of the synthesized nanomaterials. Notably, the ZCMn4 NSs exhibited minimal hemolytic activity, with a lysis rate of only 0.33% at a dosage of 500 μg/mL. The doped and dual-doped ZnS NSs exhibited strong and selective cytotoxic effects against melanoma cells while sparing normal melanocytes. Furthermore, a TUNEL assay was performed to confirm that the reduction in cell viability resulted from apoptotic cell death. These findings underscore the potential of Mn and Cu-doped ZnS nanosheets as promising therapeutic nanomaterials for cancer treatment, drug delivery, MRI, and other biological applications.

Polyanhydride particle-based vaccines overcome several limitations of current vaccines owing to their ability to encapsulate different types of antigenic payloads, provide tunable release kinetics of payloads, and induce protective immunity against multiple respiratory infections. In this work, two particle synthesis methods were compared by analyzing the structure and antigenicity of released proteins from particles made by these methods. Flash nanoprecipitation is a lab-scale method to synthesize protein-loaded particles. Spray drying is a scalable method that allows for the production of protein-loaded particles. The polyanhydride copolymer used for both synthesis methods was composed of a 20:80 M ratio of 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and 1,6-bis(p-carboxyphenoxy)hexane. The three proteins used in this work are bovine serum albumin (a model, globular protein), and SARS-CoV-2 spike and bovine RSV post-F protein (both clinically relevant proteins). The release kinetics of the encapsulated proteins were studied, and the structure of the released proteins was analyzed using gel electrophoresis and fluorescence spectroscopy. The antigenicity of the released spike and post-F was estimated based on the binding of positive mouse sera from previously inoculated mice. Our results indicate that both flash nanoprecipitation and spray drying resulted in particle formulations that provided a burst release of protein followed by a sustained period of release. The primary and tertiary structures and the antigenicity of the released proteins were maintained consistently across both methods. Altogether, these studies indicate that spray drying can be used to generate particles that stabilize encapsulated antigens and for at-scale particle synthesis in the future.

The promising outcome of Bone Tissue Engineering (BTE) via scaffolds for treating segmental bone defects (SBDs) has led the interdisciplinary field of Materials Science to take a new turn and explore innovative biomaterials that enhance tissue regeneration. The most recent advancement is the application of electrical stimulation with the use of conductive and piezoelectric biomaterials to develop conductive and electroactive (EA) scaffolds that activate osteoblast formation, leading to a significantly faster and more robust bone healing process. Researchers have explored plenty of biomaterials and scaffold fabrication techniques. This article presents a comprehensive review of the popular biomaterials that include Conductive Polymers (PANI, Poly-pyrrole, PEDOT), Piezoelectric Polymers (PVDF, TrFE, PLLA, PAs), Metallic Nanoparticles (NPs) (Ag, TiO₂), and Carbon-based NPs (CNTs, Graphene, Graphene Oxide) used for the development of conductive and EA biocompatible scaffolds. Various innovative conductive and electroactive scaffold fabricating methods, like 3D printing, bio-printing, electrospinning, etc., that precisely command over the conductive filler distribution, porosity, and pore size interconnectivity are highlighted. Tests explored by researchers for investigating the conductive and piezoelectric properties of the developed scaffolds and their osteogenic potential (in vitro and in vivo) are also presented. Apart from this, standard protocols for the conduction of these tests, regulatory pathways, scope for clinical translations, and their respective challenges have been reviewed. Most importantly, the review not only focuses on the material versatility and fabrication techniques but also critically analyzes the challenges involved in optimizing the biomaterials and fabrication parameters to develop bone scaffolds with the best-optimized physicochemical, mechanical, biological, and conductive properties.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and chronic inflammation. Current therapies mainly relieve symptoms but do not halt disease progression. We developed collagen hydrogels incorporating propolis-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (PROZIF) and menstrual blood-derived stem cells (MenSCs). In vitro assays evaluated microstructure, cell viability, anti-inflammatory activity, drug release, and cytoprotection. An osteoarthritis model was induced in rats by monosodium iodoacetate (MIA). Animals received intra-articular injections of hydrogels, and outcomes were assessed by histology, enzyme-linked immunosorbent assay (ELISA), knee swelling, and locomotor function. Collagen–PROZIF–MenSCs hydrogels with 2% nanoparticle content (COL-PROZIF-MenSCs-2) preserved MenSC viability, showed strong anti-inflammatory effects, and provided sustained propolis release. In vivo, this group significantly reduced cartilage degeneration, decreased tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), and increased transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF) levels compared to controls. Knee swelling was reduced, and locomotor scores improved. Combining ZIF-8 nanoparticles with MenSCs in collagen hydrogels synergistically mitigated OA progression in rats by reducing inflammation and supporting cartilage repair. This approach demonstrates promise as a localized, cell- and drug-based therapy for OA, warranting further long-term and translational studies.