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

The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.

Tissue engineered scaffolds aimed at the repair of critical-sized bone defects lack adequate consideration for our aging society. Establishing an effective aged in vitro model that translates to animals is a significant unmet challenge. The in vivo aged environment is complex and highly nuanced, making it difficult to model in the context of bone repair. In this work, 3D nanofibrous scaffolds generated by the thermally-induced self-agglomeration (TISA) technique were functionalized with polydopamine nanoparticles (PD NPs) as a tool to improve drug binding capacity and scavenge reactive oxygen species (ROS), an excessive build-up that dampens the healing process in aged tissues. PD NPs were reduced by ascorbic acid (rPD) to further improve hydrogen peroxide (H₂O₂) scavenging capabilities, where we hypothesized that these functionalized scaffolds could rescue ROS-affected osteoblastic differentiation in vitro and improve new bone formation in an aged mouse model. rPDs demonstrated improved H₂O₂ scavenging activity compared to neat PD NPs, although both NP groups rescued the alkaline phosphatase activity (ALP) of MC3T3-E1 cells in presence of H₂O₂. Additionally, BMP2-induced osteogenic differentiation, both ALP and mineralization, was significantly improved in the presence of PD or rPD NPs on TISA scaffolds. While in vitro data showed favorable results aimed at improving osteogenic differentiation by PD or rPD NPs, in vivo studies did not note similar improvements in ectopic bone formation an aged model, suggesting that further nuance in material design is required to effectively translate to improved in vivo results in aged animal models.

Calcined bone is an attractive natural material for use as a bone substitute because of its cost-effectiveness and high biocompatibility, which are comparable to that of synthetic hydroxyapatite. However, the calcination process has significantly weakened the mechanical properties. In this study, a composite of calcined bovine bone powder reinforced with silane cross-linked alginate was prepared to assess its biocompatibility, osteoconductivity, and mechanical compatibility as a bone substitute material. Culture studies with osteoblast-like cells (MC3T3-E1) showed no cytotoxicity toward the composite and exhibited general cell proliferative properties in its presence. In contrast, the composite reduced the alkaline phosphatase activity of osteoblasts but led to significant noncellular apatite deposition on the surface. In addition, quasi-static compression tests of the composite revealed mechanical properties comparable to those of human cancellous bone. The mechanical properties remained stable under wet conditions and did not deteriorate significantly even after 2 weeks of immersion in simulated body fluid at 37°C. The results show that this composite, composed of calcined bone powder and silane cross-linked alginate, is a promising bone substitute material with biocompatibility, osteoconductivity, and mechanical compatibility.

Rheumatoid arthritis (RA) requires therapeutic approaches that alleviate symptoms and inhibit the progression of joint damage. Glucocorticoids (GCs) have been a cornerstone of RA treatment, yet their use is often limited by side effects. Recent advancements suggest that liposome-based delivery systems can improve GC biodistribution, minimizing toxicity. This study introduces an innovative tool for RA treatment using prednisone-encapsulated nonphospholipid liposomes (NPLs) in combination with a hyaluronic acid (HA) hydrogel. Our methodology involved incorporating prednisone (PR) with palmitic acid and cholesterol to formulate stable NPLs using a thin-film hydration technique. The synthesized PR-NPLs, characterized by a mean size of 150 nm, demonstrated uniform distribution and higher drug encapsulation in comparison with conventional phospholipid liposomes. In vitro assays revealed that PR-NPL markedly reduced inflammatory responses in macrophages. Additionally, we successfully incorporated PR-NPL into an HA hydrogel, employing a photoinitiated cross-linking process. This novel composite offered modulable PR release, governed by the degree of hydrogel cross-linking. The developed system presents a promising advancement in RA management, especially suited for intraarticular injections. It potentially enables targeted, controlled drug release with a reduced risk of side effects, signifying a significant improvement over existing RA therapies.

With dental implant treatment becoming the gold standard, the need for effective bone augmentation prior to implantation has grown. This study aims to evaluate a bone augmentation strategy integrating three key growth factors: bone morphogenetic protein-2 (BMP-2), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Collagen scaffolds incorporating BMP-2, IGF-1, or VEGF were fabricated and categorized into five groups based on their content: scaffold alone; BMP-2 alone (BMP-2); BMP-2 and IGF-1 (BI); BMP-2, IGF-1, and VEGF (BIV); and BMP-2 and IGF-1 with an earlier release of VEGF (BI + V). The prepared scaffolds were surgically implanted into the calvarias of C57BL/6JJcl mice, and hard tissue formation was assessed after 10 and 28 days through histological, tomographic, and biochemical analyses. The combination of BMP-2 and IGF-1 induced a greater volume of hard tissue augmentation compared with that of BMP-2 alone, regardless of VEGF supplementation, and these groups had increased levels of cartilage compared with others. The volume of hard tissue formation was greatest in the BIV group. In contrast, the BI + V group exhibited a hard tissue volume similar to that of the BI group. While VEGF and CD31 levels were highest in the BIV group at 10 days, there was no correlation at the same time point between hard tissue formation and the quantity of M2 macrophages. In conclusion, the simultaneous release of BMP-2, IGF-1, and VEGF proved to be effective in promoting bone augmentation.

Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time-dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation.

The aim of this work was to analyze the effects of long-term exposure to titanium dioxide (TiO₂) micro- (MPs) and nanoparticles (NPs) (six and 12 months) on the biochemical and histopathological response of target organs using a murine model. Male Wistar rats were intraperitoneally injected with a suspension of TiO₂ NPs (5 nm; TiO₂-NP5 group) or MPs (45 μm; TiO₂-NP5 group); the control group was injected with saline solution. Six and 12 months post-injection, titanium (Ti) concentration in plasma and target organs was determined spectrometrically (ICP-MS). Blood smears and organ tissue samples were evaluated by light microscopy. Liver and kidney function was evaluated using serum biochemical parameters. Oxidative metabolism was assessed 6 months post-injection (determination of superoxide anion by nitroblue tetrazolium (NBT) test, superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation, and paraoxonase 1). Titanium (Ti) concentration in target organs and plasma was significantly higher in the TiO₂-exposed groups than in the control group. Histological evaluation showed the presence of titanium-based particles in the target organs, which displayed no structural alterations, and in blood monocytes. Oxidative metabolism analysis showed that TiO₂ NPs were more reactive over time than MPs (p < .05) and mobilization of antioxidant enzymes and membrane damage varied among the studied organs. Clearance of TiO₂ micro and nanoparticles differed among the target organs, and lung clearance was more rapid than clearance from the lungs and kidneys (p < .05). Conversely, Ti concentration in plasma increased with time (p < .05). In conclusion, neither serum biochemical parameters nor oxidative metabolism markers appear to be useful as biomarkers of tissue damage in response to TiO₂ micro- and nanoparticle deposits at chronic time points.

Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices. In this study, we characterized the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa on smooth and submicron-textured polyurethane surfaces after 1, 2, 3, and 7 days, and measured the efficacy of common antibiotics against these biofilms. Results show that the submicron-textured surfaces significantly reduced biofilm formation and growth, and that the efficacy of antibiotics against biofilms grown on textured surfaces was improved compared with smooth surfaces. The antibiotic efficacy appears to be related to the degree of biofilm development. At early time points in biofilm formation, antibiotic treatment reveals reasonably good antibiotic efficacy against biofilms on both smooth and textured surfaces, but as biofilms mature, the efficacy of antibiotics drops dramatically on smooth surfaces, with lesser decreases seen for the textured surfaces. The results demonstrate that surface texturing with submicron patterns is able to improve the use of standard antibiotic therapy to treat device-centered biofilms by slowing the development of the biofilm, thereby offering less resistance to antibiotic delivery to the bacteria within the biofilm community.

In this study, we evaluated the drug release behavior of diameter customized TiO₂ nanotube layers fabricated by anodization with various applied voltage sequences: conventional constant applied potentials of 20 V (45 nm) and 60 V (80 nm), a 20/60 V stepped potential (50 nm [two-diameter]), and a 20–60 V swept potential (49 nm [full-tapered]) (values in parentheses indicate the inner tube diameter at the top part of nanotube layers). The structures of the 50 nm (two-diameter) and 49 nm (full-tapered) samples had smaller inner diameters at the top part of nanotube layers than that of the 80 nm sample, while the outer diameters at the bottom part of nanotube layers were almost the same size as the 80 nm sample. The 80 nm sample, which had the largest nanotube diameter and length, exhibited the greatest burst release, followed by the 50 nm (two-diameter), 49 nm (full-tapered), and 45 nm samples. The initial burst released drug amounts and release rates from the 50 nm (two-diameter) and 49 nm (full-tapered) samples were significantly suppressed by the smaller tube top. On the other hand, the largest proportion of the slow released drug amount to the total released drug amount was observed for the 50 nm (two-diameter) sample. Thus, 50 nm (two-diameter) achieved suppressed initial burst release and large storage capacity. Therefore, this study has, for the first time, applied TiO₂ nanotube layers with modulated diameters (two-diameter and full-tapered) to the realization of a localized drug delivery system (LDDS) with customized drug release properties.