Journal of biomedical materials research. Part A最新文献

Osteoarthritis (OA) is a progressive joint disease that involves damage to the cartilage, inflammation in the synovium, and injury to the subchondral bone, which highlights the need for the creation of novel treatment options. Nevertheless, finding an effective method that combines anti-inflammatory properties with the ability to regenerate cartilage remains a significant challenge. TA@Sr²⁺ is a bioactive coordination complex formed through chelation between tannic acid (TA) and strontium ions (Sr²⁺), exhibiting a hierarchically structured metal-phenolic network. This research presents an innovative strategy utilizing a Macrophage_nex developed from multifunctional TA@Sr²⁺, which promotes chondrogenesis and exhibits strong anti-inflammatory effects. The Macrophage_nex based on TA@Sr²⁺ is constructed by self-assembling a single-cell layer using varying concentrations of TA and Sr²⁺ on RAW264.7 cell surfaces. This Macrophage_nex demonstrates robust biological activity, enhancing chondrocyte proliferation, differentiation, and migration, alongside the upregulation of anabolic genes such as aggrecan (ACAN) and collagen II, while simultaneously inhibiting the expression of catabolic genes like MMP13 in a dose-dependent manner under LPS-induced inflammation. In addition, TA@Sr²⁺ reduces the expression of proinflammatory cytokines (TNF-α and IL-6) in macrophages and promotes their polarization to the anti-inflammatory M2 phenotype. These results suggest that TA@Sr²⁺ has significant promise for treating OA by regulating both chondrogenesis and macrophage polarization simultaneously.

Cellular entrapment within biostable hydrogels can decrease immunological rejection by blocking direct contact between the host and transplanted cells; however, these implants remain susceptible to deleterious inflammatory and immunological responses that can dampen their therapeutic effect. Reactive oxygen species (ROS) are key agents that facilitate these responses. While ROS is commonly attributed to general inflammation and cytotoxicity, it also plays an important role in the activation of adaptive immune cells, as ROS-mediated pathways facilitate the efficient generation of effector T cells. Herein, we explored if incorporating a potent antioxidant, specifically cerium oxide nanoparticles (CONP), onto the surface of a hydrogel-based microbead platform could deliver an immunomodulatory biomaterial capable of dampening antigen-specific effector T cell generation. To test this hypothesis, CONP-based coatings were applied to the surface of cell-containing alginate microbeads and co-cultured with immune cells. Quantification of the immune responses found that CONP-coatings decreased the generation of antigen-specific effector CD8⁺ T cells. Interrogation of T cell and antigen-presenting cell (APC) responses found suppression was likely driven by the modulation of CD8⁺ T cells, as APCs were only modestly impacted. Results provide insight into the capacity of CONP to deliver an immunomodulatory effect. These findings also highlight the general potential of antioxidant biomaterials to serve a dual role in protecting cells from ROS-mediated damage and suppressing adaptive immune cell responses.

Drug delivery systems (DDSs) have grown in popularity for their astute ability to encapsulate a drug into a biocompatible carrier, thus improving targeted and localized delivery to specific tissues. DDSs often increase circulation time and therapeutic effects while also decreasing systemic side effects. In diseases that are difficult to treat with conventional therapies, such as endometrial cancer, DDSs are a promising therapeutic alternative. In this study, a polycaprolactone (PCL) particle loaded with the chemotherapeutic paclitaxel (PTX) was generated as a DDS and investigated for efficacy in the Ishikawa and KLE endometrial cancer cell lines. Dye-loaded particles were used to quantify particle uptake and identify cellular localization. Results indicated that polymeric encapsulation of PTX was achieved and approximately 22% of the cargo was released in the first 48 h, followed by at least 28 days of sustained release. These particles enhanced antiproliferative activity in cells at lower PTX concentrations compared with the free drug. Using a dye-loaded particle, confocal microscopy confirmed intracellular localization of the dye, particularly in the nucleus and cytoplasm, which was also quantified using fluorescence. These data indicate that PCL is a potential polymer for further development of DDS for cancer therapeutics.

Surgical meshes are medical devices that were initially designed for hernia repair and later adopted for pelvic floor reconstructive surgeries, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Polypropylene (PP) is the most common material for surgical mesh, but others have been used clinically. Complications with PP surgical mesh have been attributed to several factors, including the post-implantation degradation of the surgical mesh materials. PP mesh was initially considered to be inert, but evidence of in vivo degradation has since been widely reported in retrieved surgical mesh after long-term implantation. This review provides an overview of the physical and mechanical properties of surgical mesh prior to implantation and the post-implantation stability of the mesh materials. We underscore the need to consider the changes in mesh properties after implantation and their potential effects on device safety. This review highlights the importance of characterizing “effective porosity,” assessing mechanical properties under physiological stresses, understanding the in vivo degradation mechanisms, employing accelerated bench-top aging methods to estimate long-term biostability, and developing in vitro in vivo correlations (IVIVC) to minimize resource-intensive long-term testing and improve patient access to innovative devices. Overall, this review provides a materials science perspective on the research gaps that could be considered in future iterations of surgical mesh devices to improve their safety and performance.

Despite the great potential of citrate polyesters in regenerative medicine, the data about their application in electrospinning is somewhat limited. In this work, poly(dimethylene citrate) (P-1,2-ECit), poly(tetramethylene citrate) (P-1,4-BCit), and poly(hexamethylene citrate) (P-1,6-HCit) were synthesized. Nonwovens from poly(diol citrates)/PLA mixtures were successfully electrospun and characterized using SEM, AFM, water contact angle measurement, DSC, TGA, and in vitro degradation tests. The addition of poly(diol citrates) increases the hydrophilicity and surface adhesion force of PLA nonwovens; however, the observed effects depend on the scale level (macro/micro) of the analysis. Diol chain length in poly(diol citrate) influences the compatibility and heterogeneity of its distribution within the carrier polymer. Additionally, it impacts the crystallinity of the PLA phase. Degradation tests show the problem of the nonwoven stability in the aqueous media and the high leachability of the short-chained poly(diol citrates). Addressing this issue is important regarding controlling the degradation kinetics. Despite the good processability in electrospinning and promising surface properties of the poly(diol citrates)/PLA mixtures, the instability of these materials in an aqueous environment is an important issue which can subsequently affect the performance of the eventual implant/cell scaffold. The solution may involve chain elongation of the hydrophilic oligomeric additive.

Dysregulation of pro-inflammatory cytokines participates in the initiation and development of knee osteoarthritis (OA). Consequently, interventions to boost the anti-inflammatory capacity of articular chondrocytes have been proposed to treat early-stage OA and prevent OA progression. Applying nanoencapsulation can enhance bioavailability and bioactivity and sustain the anti-inflammatory activity of phytochemicals. Accordingly, in this study, we used nanocapsules to deliver curcumin (Cur) to treat inflammatory chondrocytes. Using double-emulsion technology, Cur was encapsulated in chitosan-coated poly(lactic-co-glycolic acid) nanocapsules. The nanocapsulized Cur (NCcur) was characterized, and the toxicity to human articular chondrocytes was evaluated. NCcur was applied to interleukin-1 beta (IL-1β)-stimulated cells based on findings of the Cur toxicity study. Results showed that the particle size of NCcur was 247.8 ± 1.73 nm with a zeta potential of 20.3 ± 0.11 mV and a mid-range distribution. NCcur showed a core-shell and sphere-like morphology. The encapsulation efficiency of Cur in nanocapsules was 67.1%. Nanoencapsulation decreased the toxicity of high-dose Cur (> 20 μM), and NCcur exhibited a sustained Cur release over 72 h. NCcur supplementation (20 μM) improved cell survival and ameliorated cell senescence of inflammatory chondrocytes. The IL-1β-induced IL1B, IL6, metalloproteinase-9 (MMP9), and MMP13 mRNA expressions were down-regulated, while IL10 level was enhanced in NCcur-treated chondrocytes. Likewise, NCcur supplementation restored aggrecan, collagen type II alpha 1 chain, and SOX9 mRNA expressions. MMP-13, IL-8, and MCP-1 secretions in the supernatant also decreased. By applying nanocapsules, we assumed the anti-inflammatory capacity of Cur could be sustained for treating knee OA.

Several studies have investigated the location of transplanted cells and tissue-engineered cell constructs in the body by incorporating contrast nanoparticles into cells by endocytosis; however, these have yet to be applied clinically because of the complexity of assessing the safety of nanoparticles. In this study, we proposed that our developed adherent cell self-aggregation technique (CAT) could be used to develop cell aggregates loaded with contrast particles of a size that would exclude the possibility of endocytosis, and aimed to prepare these aggregates followed by biological and computed tomography (CT) contrast evaluation under X-rays. Once human bone marrow-derived mesenchymal stem cells (HBMSCs) were seeded into culture dishes coated with CAT-inducing polymer to form gapless cell monolayer sheets, tungsten carbide (WC) particles smaller than 1 μm or titanium (Ti) particles larger than 10 μm were added, and thus each particle deposited on the surface of the cell monolayer sheet. During the subsequent overnight incubation, spontaneous detachment and aggregation of the cell monolayer sheets with deposited WC and Ti particles occurred, forming single spherical cell aggregates (spheroids) and loading these particles. Histological analysis confirmed that Ti particles with a diameter of at least 10 μm were not endocytosed and remained attached to the outside of cells forming spheroids, while WC particles were endocytosed into the cells. The CT images of the Ti-loaded spheroids were clearly visible along the spheroid shape under X-ray irradiation. Then, we confirmed that there was no toxicity to the cells forming the spheroids by loading Ti particles, and the cells could sprout and proliferate by culturing the spheroids. We successfully prepared Ti particle-loaded HBMSCs aggregates with long fiber shape (> 10 cm) by applying CAT to a culture dish with a ring-fiber-shaped culture groove and confirmed their clear visibility on CT images under X-ray irradiation, as well as their containment and ejection into a catheter, demonstrating their applicability to catheter-mediated regenerative therapy.

The identification of materials that effectively promote mineralization and vascularization is crucial for advancing clinical applications in bone regeneration. Biomimetic silicified collagen scaffold (SCS) has emerged as a promising candidate, demonstrating significant potential to enhance both osteogenesis and angiogenesis. However, the mechanisms by which SCS directly influences angiogenesis to facilitate bone defect healing remain largely unexplored. In this study, we observed that the implantation of SCS in rabbit femoral defects resulted in extensive bone regeneration and angiogenesis at the wound sites. Notably, SCS outperformed commercial alternatives such as Bio-Oss in terms of degradation and angiogenic response. In vitro assays further demonstrated that SCS upregulates angiogenic protein expression and promotes endothelial cell angiogenesis through the activation of the HIF-1α/VEGF signaling pathway. Consequently, SCS modulates the phenotype of vascular endothelial cells, leading to the formation of CD31^hiEmcn^hi type H endothelial cells, which are critical for effective bone regeneration. This study offers valuable perspectives on the dual effects of silicified materials on osteogenesis and angiogenesis, advancing the understanding of their potential functions in regenerative medicine.