Journal of biomedical materials research. Part A最新文献

Vaccine development requires innovative approaches to improve immune responses while reducing the number of immunizations. In this study, we explore the impact of controlled antigen release on immune activation and regulation using programmable infusion pumps and biodegradable biomaterials in OT-II and wild-type mice to understand the adaptive immune response through controlled antigen delivery in the absence of adjuvant. Ovalbumin (OVA) was delivered via an exponentially decreasing profile, mimicking clearance of infection, and an exponentially increasing profile, mimicking induction of infection. Exponentially decreasing OVA delivery through infusion pumps promoted regulatory T-cell (Treg) activation in secondary lymphoid organs and suppressed pro-inflammatory T-helper type 17 (Th17) responses in blood. An exponentially increasing OVA profile enhanced central memory T-cell (TCM) populations in submandibular blood and humoral immune responses in cardiac blood serum, demonstrating distinct immune modulation based on release kinetics. OVA was also delivered using a biodegradable PLGA-PEG-PLGA (PPP) depot, which provided controlled OVA release in an exponentially decreasing pattern. PPP-OVA treatment significantly reduced the frequency of pro-inflammatory T-helper type 1 (Th1) cells while increasing CD25⁺FOXP3⁺ Treg cells in the spleen. Moreover, to identify T-cell populations that most accurately characterize the divergence in Treg and T-helper response to OVA kinetics, a Sequential Feature Selection (SFS) algorithm with Machine Learning (ML) models was used. ML algorithms identified gMFI of RORγt⁺ as a key feature in submandibular blood and the ratio of gMFI of FOXP3⁺ to GATA3⁺ as the marker that was significantly changed by treatments in inguinal lymph nodes (iLN) when infusion pumps were used to deliver OVA. In addition, ML-based SFS identified CD25⁺FOXP3⁺ regulatory T cells as the most important feature, influencing the expression of other cell types in both inguinal lymph nodes (iLN) and spleen when PPP was used to deliver OVA. This finding suggests that the exponentially decreasing profile may generate anti-inflammatory responses. Overall, these findings suggest that controlled antigen delivery enhances immune regulation and memory T cells, providing new insights into immune responses mediated by the release kinetics.

This work highlights the potential of porous, bioactive coatings to advance implant technology and address critical clinical challenges. A key issue in implant coatings is to achieve the balance between infection prevention and successful osseointegration. Although titanium implants are widely used due to their mechanical strength and biocompatibility, their bioinert nature limits integration with bone tissue. To address these issues, porous calcium phosphate (CaP) coatings have been developed to enhance cell attachment and bone growth. However, CaP, especially in the widely used form of hydroxyapatite (HAp), has a low resorption rate, which often leads to prolonged coating stability and impairs natural bone remodeling. To overcome this limitation, magnesium phosphate (MgP), an underexplored but promising biomaterial with high biocompatibility and osteogenic potential, can be introduced. Another innovative strategy is the doping of biomaterials with antibacterial ions, among which copper (Cu) has attracted particular attention. The incorporation of Cu into the coating matrix can significantly reduce the risk of post-operative infection while promoting angiogenesis, a key factor for rapid and stable implant integration. This study presents bone implant coatings composed of tricalcium phosphate (TCP) and Cu-doped MgP clustered nanoparticles (supraparticles) fabricated via high-velocity suspension flame spraying (HVSFS). This particle system addresses current challenges in bone tissue regeneration by synergistically combining the high biodegradability of MgP, the bone-mimicking properties of CaP, and the antibacterial capabilities of Cu. In addition, the HVSFS process enables the creation of thin layers with porous microstructures. Biocompatibility of the prepared coatings was assessed using MG63 osteosarcoma cells, while the antibacterial efficacy was tested against Staphylococcus aureus and Escherichia coli. The incorporation of Cu-doped MgP supraparticles (MgPCu and MgPCu HT) into TCP coatings resulted in high Cu release and pronounced antibacterial efficacy compared to the TCP reference, while the addition of Cu-doped FT supraparticles (FTCu) led to high cell proliferation.

Bioprinting is a growing area in the field of tissue engineering that offers a potential solution to the global shortage of organ transplants. Ensuring high printability is crucial for bioprinting. To better understand printability, a design of experiment model that examines printing speed and pressure in extrusion-based printing was developed. Two biomaterials, hyaluronic acid and sodium alginate, were selected as surrogate biomaterials to understand how rheological properties play a role in printability. Various rheological aspects such as shear-thinning behavior, viscosity, and recovery were investigated. To further evaluate printability, a new method was used that includes deep learning image similarity. The information obtained with the surrogate bioinks was then applied to another biomaterial, methacrylated hyaluronic acid, in combination with corneal keratocytes to demonstrate the successful implementation of the outcome of this design of experiment. As a result of this study, a better understanding of the rheological properties for bioprinting was achieved, leading to a next step towards improving extrusion-based bioprinting, which can be used for a wide range of applications.

Additive manufacturing of patient specific implants made of biodegradable polymers is receiving increasing attention in the medical sector, including the trend towards manufacturing at the point-of-care. Despite this, the changes of the polymer structure and their effects on mechanical properties and degradation behavior caused by the additive manufacturing process and subsequent sterilization are still insufficiently investigated, although of key relevance for the implant's functionality. In this study, poly(p-dioxanone) (PPDO) was processed by fused filament fabrication (FFF). The effects of manufacturing as well as two different low-temperature sterilization techniques, namely H₂O₂ plasma and gamma irradiation, on the polymer structure were evaluated. Additionally, PPDO degradation was investigated by immersing the processed samples in Sorensen's phosphate buffer (PB) with pH = 6.47 for 28 days to mimic implantation in intestinal milieu and evaluated at regular time intervals. Results showed that we were able to successfully print PPDO without influencing the polymer structure or cytocompatibility. No significant changes were detected for plasma-sterilized samples (PS) while gamma-sterilized (GS) ones significantly decreased molecular weight (M_w and M_n) and showed significant lower inherent viscosity (IV) compared with the (non-sterilized) control group after processing. During immersion in PB, a decrease in M_w, M_n, and mechanical strength occurred for all samples. However, GS samples were affected to a much higher extent compared with the other groups both in final values and timeline. A degradation plateau was seen for the tensile strength of NS and PS samples over the first 21 and 17 days, respectively, followed by a steady decrease. In contrast, for the GS samples, a drastic decrease in tensile strength occurred already during the first 14 days. There was no notable mass loss detected within the first 28 days of degradation for any of the sample groups. Based on these results, we conclude that FFF with subsequent plasma sterilization is a reliable process for manufacturing PPDO devices for short-term applications that require stable mechanical conditions within the first weeks of implantation to guarantee the time needed for tissue healing before degrading, as for example, in the case of intestinal compression anastomoses. Such requirement could not be met with gamma sterilization with the dose used, because of the too fast decrease in mechanical properties.

Implantable neural prosthetics with stimulating electrodes are increasingly employed in medical practices to treat neural disabilities. The electrode material is expected to provide high charge storage and injection capacity (CSC/CIC) and low impedance for safe, efficient, and precise neural stimulation, while at the same time, being small. To improve the current state-of-the-art neural-electrode material, iridium oxide (IrOx), Ir_mBi_1-mOx coatings of various compositions (m = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) produced by thermal deposition were evaluated. The Ir_0.8Bi_0.2Ox yielded a CSC of 17.7 ± 1.1 mC/cm², which is four-fold higher than that of IrOx. At the same time, the impedance of Ir_0.8Bi_0.2Ox at 1 kHz was measured to be half of that of IrOx. The superior performance of Ir_0.8Bi_0.2Ox was explained by forming amorphous structures that facilitate the intercalation of H⁺ and OH⁻ ions into deeper oxide structures that contribute to faradaic charge storage. The Ir_0.8Bi_0.2Ox electrode also showed good stability and biocompatibility, which makes it potentially a good candidate for neural stimulating electrodes.