Journal of biomedical materials research. Part A最新文献

Bone tissue regeneration can be affected by various architectonical features of 3D porous scaffold, for example, pore size and shape, strut size, curvature, or porosity. However, the design of additively manufactured structures studied so far was based on uniform geometrical figures and unit cell structures, which often do not resemble the natural architecture of cancellous bone. Therefore, the aim of this study was to investigate the effect of architectonical features of additively manufactured (aka 3D printed) titanium scaffolds designed based on microtomographic scans of fragments of human femurs of individuals of different ages on in vitro response of human bone-derived mesenchymal stem cells (hMSC). Four different types of titanium scaffold (33Y, 48Y, 56Y, and 63Y, where the number indicates the age of the individual) were fabricated using laser beam powder bed fusion (PBF-LB) and characterized with respect to the dimensional features, permeability, and stiffness. hMSC were seeded onto the scaffolds and MTS, DNA, alkaline phosphatase, and alizarin red assays were used to study cell viability, proliferation, and osteogenic differentiation. Microcomputed tomography revealed that the largest average pore size was in scaffolds 63Y (543 ± 200 μm), which was nearly twice as large as the smallest pores in scaffolds 56Y. Moreover, scaffolds 63Y exhibited the highest porosity (~61%), while the other architectures had porosity of ~43%–44%. Scaffolds 63Y also had the lowest surface area-to-volume ratio (11.07 ± 0.05 mm⁻¹), whereas scaffolds 56Y had the highest (14.80 ± 0.06 mm⁻¹). Furthermore, scaffolds 33Y had the largest strut size (398 ± 124 μm), exceeding the size in scaffolds 56Y (the smallest strut size) by over 1.5 times. CFD simulations indicated that the hydraulic permeability was the highest for scaffolds 63Y (5.24 × 10⁻⁹ m²; order of magnitude higher than in the other architectures). Stiffness of the investigated scaffolds, determined by finite element modeling, ranged from ~29 GPa (63Y) to ~60 GPa (56Y). This study demonstrates that the highest manufacturing accuracy in 3D printed structures based on architectural designs inspired by cancellous bone could be achieved when the structures were characterized by moderate strut sizes, the largest pores, and the highest porosity and permeability. The scaffold with the highest porosity and permeability (i.e., 63Y) yielded the lowest cell retention. Regarding the osteogenic differentiation, a correlation was found between the mineralization of the deposited extracellular matrix and the hydraulic permeability, pore size, and surface area-to-volume ratio but not the porosity.

Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other breast cancer subtypes. One factor contributing to this poor prognosis is that TNBC lacks expression of the receptors that available hormonal or molecular-oriented therapies attack. New treatments that exploit biological targets specific to TNBC are desperately needed to improve patient outcomes. One promising target for therapeutic manipulation is the Wnt signaling pathway, which has been associated with many invasive breast cancers, including TNBC. This pathway is activated in TNBC cells when extracellular Wnt ligands bind to overexpressed Frizzled7 (FZD7) transmembrane receptors, leading to downstream activation of intracellular β-catenin proteins. To target and inhibit Wnt signaling in TNBC cells, polymer nanoparticles (NPs) modified with anti-FZD7 antibodies and β-catenin small interfering RNAs (siRNAs) were developed, and their impact on the oncogenic behavior of treated TNBC cells was investigated. When compared to control NPs, the Wnt-targeted NPs induced greater levels of Wnt oncogene suppression. This led to greater inhibition of oncogenic and stem-like properties, including cell proliferation, drug resistance, and spheroid formation capacity. This work demonstrates a promising approach for targeting the Wnt pathway in TNBC to counter the cellular phenotypes that drive disease progression.

Dental implant coronal surfaces designed with the primary goal of maintaining crestal bone levels may also promote bacterial adhesion, leading to soft tissue inflammation and peri-implant bone loss. Achieving an optimal surface roughness that minimizes bacterial adhesion while preserving crestal bone is crucial. It is hypothesized that a specific threshold surface roughness value may exist below which, and above which, initial bacterial adhesion does not statistically change. This study evaluated 12 commercially available and 2 custom-designed implant surfaces for their physicochemical properties and initial bacterial adhesion, as represented by Streptococcus oralis (S. oralis) the dominant initial colonizer of the successive waves of bacterial consortia that result in plaque and biofilm formation. Implants were immersed in a S. oralis suspension for 4 h, after which microbial viability was assessed. Marked differences were observed in surface roughness, chemical composition, and wettability, and S. oralis adhesion. Surfaces with Sa > 1 μm had significantly more adherent bacteria after 4 h compared to those with Sa < 1 μm, despite complexity. Adding nanotopography to dual-acid etched surfaces further reduced bacterial adhesion compared to surfaces without these features. The role of chemical composition and wettability was less influential than roughness. In conclusion, there is a cut-off threshold roughness around Sa = 1 μm, above which the adhesion of bacteria increases significantly to a plateau level; while below which, bacterial adhesion is equivalent to a machined surface despite the surface texture of the implant collar.

In situ gelling, cell-laden hydrogels hold promise for regenerating tissue lesions with irregular shapes located in complex and hard-to-reach anatomical sites. A notable example is the regeneration of neural tissue lost due to cerebral cavitation. However, hypoxia-induced cell necrosis during the vascularization period imposes a significant challenge to the success of this approach. Oxygen-releasing hydrogels have been developed to address this issue, but they suffer from fast oxygen release over a short period, limiting their efficacy. This study develops an in situ gelling hydrogel system based on silk fibroin (SF) and decellularized brain extracellular matrix (dECM) with sustained oxygen release and tunable gelation time. Calcium peroxide nanoparticles (CPO NPs) served as the oxygen generating material, which were encapsulated within SF microparticles before incorporation into the SF-dECM hydrogel, aiming to regulate the oxygen release rate. The total CPO content of the hydrogels was only 2%–4% w/w. Characterization of hydrogels containing various SF concentrations (2%, 4% or 6% w/v) and microparticle loadings (10%, 15% or 20% w/w) demonstrated that SF concentration in the hydrogel matrix significantly affects the swelling, resorption rate and mechanical properties, while microparticle loading has a milder effect. On the other hand, microparticle loading strongly affected the oxygen release profile. High SF concentration in the hydrogel matrix (6% w/v) led to slow resorption rate and high stiffness, likely unsuitable for intended application. Low SF concentration (2% w/v), on the other hand, led to a high swelling ratio and a less sustained oxygen release. Among 4% w/v SF hydrogels, increased microparticle loading led to a slower resorption rate, increased stiffness and enhanced oxygen release. However, cell viability was reduced at 20% w/w microparticle loading, likely due to decreased cell attachment. The 4% w/v SF hydrogels containing 10% w/w SF-CPO microparticles exhibited relatively low swelling ratio (12.8% ± 2.4%), appropriate resorption rate (70.16% ± 10.75% remaining weight after 28 days) and compressive modulus (36.9 ± 1.7 kPa) and sustained oxygen release for over 2 weeks. This sample also showed the highest viability under hypoxic conditions among tested hydrogel samples (87.6% ± 15.9%). Overall, the developed hydrogels in this study showed promise for potential application in brain tissue engineering.

Basic fibroblast growth factor (bFGF) is a significant member of the fibroblast growth factor (FGF) family. The bFGF has a three-dimensional structure comprising 12 reverse parallel β-folds. This structure facilitates tissue wound repair, angiogenesis, bone formation, cartilage repair, and nerve regeneration. Consequently, it has garnered significant attention from scholars both domestically and internationally. However, the instability and degradation properties of bFGF in vivo have limited its clinical application. Significant interest has arisen in the development of novel bFGF delivery systems that can address the shortcomings of bFGF and enhance its bioavailability by controlling the release amount, timing, and location. This article offers a comprehensive overview of the research and recent advances in various bFGF delivery systems, including hydrogels, liposomes, microspheres, and nanoparticles. Subsequently, the applications of bFGF pharmaceutical preparations in various fields are described. Finally, the current clinical applications of bFGF drug formulations and those in clinical trials are discussed, along with their clinical translation and future trends.

Long-term electrocardiogram (ECG) monitoring is crucial for detecting and diagnosing cardiovascular diseases (CVDs). Monitoring cardiac health and activities using efficient, noninvasive, and cost-effective techniques such as ECG can be vital for the early detection of different CVDs. Wet electrode-based traditional ECG techniques come with unavoidable limitations of the altered quality of ECG signals caused by gel volatilization and unwanted noise followed by dermatitis. The limitation related to the wet electrodes for long-term ECG monitoring in static and dynamic postures reminds us of the urgency of a suitable substitute. Dry electrodes promise long-term ECG monitoring with the potential for significant noise reduction. This review discusses traditional and alternative techniques to record ECG in terms of meeting the efficient detection of CVDs by conducting a detailed analysis of different types of dry electrodes along with materials (substrate, support, matrix, and conductive part) used for fabrication, followed by the number of human subjects they have been used for validation. The degradation of these electrodes has also been discussed briefly. This review finds a need for more validation on a sufficient number of subjects and the issue of cost and noise hindering the commercialization of these dry electrodes.

Precise blood glucose control continues to be a critical challenge in the treatment and management of type 1 diabetes in order to mitigate both acute and chronic complications. This study investigates the development of a supramolecular peptide amphiphile (PA) material functionalized with phenylboronic acid (PBA) for glucose-responsive glucagon delivery. The PA-PBA system self-assembles into nanofibrillar hydrogels in the presence of physiological glucose levels, resulting in stable hydrogels capable of releasing glucagon under hypoglycemic conditions. Glucose responsiveness is driven by reversible binding between PBA and glucose, which modulates the electrostatic interactions necessary for hydrogel formation and dissolution. Through comprehensive in vitro characterization, including circular dichroism, zeta potential measurements, and rheological assessments, the PA-PBA system is found to exhibit glucose-dependent assembly, enabling controlled glucagon release that is inversely related to glucose concentration. Glucagon release is accelerated under low glucose conditions, simulating a hypoglycemic state, with a reduced rate seen at higher glucose levels. Evaluation of the platform in vivo using a type 1 diabetic mouse model demonstrates the efficacy in protecting against insulin-induced hypoglycemia by restoring blood glucose levels following an insulin overdose. The ability to tailor glucagon release in response to fluctuating glucose concentrations underscores the potential of this platform for improving glycemic control. These findings suggest that glucose-stabilized supramolecular peptide hydrogels hold significant promise for responsive drug delivery applications, offering an approach to manage glucose levels in diabetes and other metabolic disorders.

Conventional two-dimensional (2D) cardiomyocyte differentiation protocols create cells with limited maturity, which impairs their predictive capacity and has driven interest in three-dimensional (3D) engineered cardiac tissue models of varying maturity and scalability. Cardiac spheroids are attractive high-throughput models that have demonstrated improved functional and transcriptional maturity over conventional 2D differentiations. However, these 3D models still tend to have limited contractile and electrical maturity compared to highly engineered cardiac tissues; hence, we incorporated a library of conductive polymer microfibers in cardiac spheroids to determine if fiber properties could accelerate maturation. Conductive microfibers improved contractility parameters of cardiac spheroids over time versus nonconductive fibers, specifically, when they were short, for example, 5 μm, and when there was moderate fiber mass per spheroid, for example, 20 μg. Spheroids with optimal conductive microfiber length and concentration developed a thicker ring-like perimeter and a less compacted cavity, improving their contractile work compared to control cardiac spheroids. Functional improvements correlated with increased expression of contractility and calcium handling-related cardiac proteins, as well as improved calcium handling abilities and drug response. Taken together, these data suggest that conductive microfibers can improve cardiac spheroid performance to improve cardiac disease modeling.