Journal of biomedical materials research. Part A最新文献

Precision porous scaffolds hold promise for tissue engineering and regenerative medicine due to their ability to support cell ingrowth and vascularization and mitigate the foreign body reaction (FBR). In previous work, we demonstrated that vat photopolymerization 3D printing enables the fabrication of porous scaffolds with 40 μm interconnected cubical pores. This study aims to do a preliminary evaluation of cellular responses and the FBR to 3D-printed scaffolds with 40 μm cubical pores, in comparison with template-fabricated spherical pores (optimized for healing) and non-porous slabs (negative control). The results indicate that porous scaffolds, regardless of pore geometry, outperform non-porous structures in mitigating the FBR, promoting tissue regeneration, and triggering vascularization. This is the first paper demonstrating the pro-healing property of high-resolution 3D-printed 40 μm cubical pore scaffolds. These findings underscore the potential of 3D-printed porous scaffolds to advance patient-specific therapies, support soft (such as brain and blood vessel) and hard tissue (such as bone) repair, and improve healing outcomes in regenerative medicine applications.

Developing multifunctional biomaterials with both electrical and biological properties is crucial for next-generation biomedical platforms. This study looks into how Cu/Zn co-doping affects the structural, electrical, and biological performance of hydroxyapatite (Ca_10-x-yZn_xCu_y(PO₄)₆(OH)₂; x = y = 0.2–1.2), which was synthesized through a solid-state reaction. Among the samples, the CZ6 composition (x = y = 0.6) showed the best properties. It had a single-phase hexagonal structure, a nanoscale crystallite size of about 32 nm, a d-spacing of 0.27 nm along the (112) plane, and a grain size that ranged from 300 to 1200 nm while still keeping the proper composition. Electrical tests showed that CZ6 had the highest dielectric constant of 14.06 at 1 MHz. It maintained a low and stable loss tangent (~0.01), lower grain boundary resistance, and improved AC conductivity (from 10⁻⁷ to 10⁻⁶ S/cm), indicating better charge transport. These electrical enhancements correlate strongly with improved biological responses. CZ6 displayed strong apatite formation in simulated body fluid, the highest BSA protein adsorption of 25.05 μg/mL, and an optimized zeta potential of −30.54 mV, which facilitates enhanced biomolecular interactions. Cytocompatibility tests with PSVK-1 (skin keratinocytes) and Wi-38 (lung fibroblasts) confirmed that cell viability remained high at all concentrations. While higher levels of dopants led to the formation of secondary phases and diminished biological responses, CZ6 kept a good balance between electroactivity and biofunctionality. These findings make CZ6 a promising electroactive bioceramic for bone tissue engineering, smart implant coatings, and bioelectret scaffolds, where combining electrical responsiveness with cellular compatibility is important.

Osteochondral defects (OCDs) present significant clinical challenges, necessitating scaffolds that effectively regenerate both cartilage and subchondral bone. We developed a bilayer scaffold using fish collagen extracted from Catla catla skin to overcome the limitations of conventional biomaterials, such as mammalian collagen and synthetic polymers, which often suffer from immunogenic risks, poor bioactivity, or inadequate structural integration. The scaffold is comprised of collagen/fibrin (CC/FIB) for the articular cartilage layer and collagen/sodium citrate/hydroxyapatite (CC/NAC/HAP) for the subchondral bone layer, which is cross-linked with citric acid. Physicochemical characterization confirmed scaffold integration, enhanced thermal stability, and a porous architecture. The scaffold demonstrated optimal porosity (63.12%), degradation (62.08% over 28 days), superior swelling potential, and enhanced bio-mineralization in simulated body fluid. In vitro studies using MG-63 osteoblast-like cells and MC3T3-E1 cells showed high biocompatibility, increased alkaline phosphatase activity, and enhanced calcium deposition (33.73 ± 0.53 μg/mg of protein at 21 days). Gene expression analysis revealed upregulation of osteogenic (COL I ~23-fold, RUNX-2 ~15-fold, OCN ~8-fold) and chondrogenic (COL II ~12-fold, SOX-9 ~10-fold, ACAN ~6-fold) markers, confirming osteochondral regeneration potential. In vivo studies involving the implantation of 3 mm femoral trochlear OCDs in albino Wistar rats (n = 3 per group) resulted in substantial bone and cartilage regeneration, with complete defect closure by 12 weeks. Radiographic and histological assessments at 4, 8, and 12 weeks confirmed well-organized osteochondral repair, demonstrating superior regenerative capability compared to control groups. This study establishes the novelty of the fish collagen-based bilayer scaffold as a promising candidate for osteochondral tissue engineering, supporting effective cartilage and subchondral bone regeneration in OCD treatment.

Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recruitment to neural injury sites and may contribute to neural repair. However, SDF-1a has a short half-life and requires a delivery system to both protect and sustain its release. Here, we sought to develop a drug delivery platform capable of releasing SDF-1a in a controlled fashion while minimizing inflammation. We used modified hyaluronic acid and microfluidics to generate monodisperse microgels. Characterization of these microgels included size, tunability, degradation, and controlled release properties. Finally, we delivered SDF-1a-loaded microgels to a mouse model of traumatic brain injury at 7 days post-injury and assessed their impact on neural progenitor cell recruitment and astrogliosis. The microfluidic system generated highly monodisperse microgels that successfully encapsulated a matrix metalloproteinase (MMP)-cleavable SDF-1a peptide and retained sensitivity to collagenase. Following intracortical injections, the microgels did not exacerbate the astrocytic response compared to saline injections; no significant difference was observed in neural progenitor cell migration patterns compared to controls. Therefore, we developed a biocompatible microgel system that is highly adaptable for biological delivery and may be utilized in brain/neural applications without exacerbating neuroinflammation.

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.