Journal of Biomaterials Applications最新文献

The long non-coding RNA HOTAIR and the Hedgehog-Gli1 signaling pathway are closely associated with tumor occurrence and drug resistance in various cancers. However, their specific roles in the development of EGFR-TKIs resistance in non-small cell carcinoma remain unclear. To address the issue of EGFR-TKIs resistance, this study utilized the electrospray method to prepare sodium alginate microspheres encapsulating HOTAIR siRNA (SA/HOTAIR siRNA) and investigated its effects on RNA interference (RNAi) in the gefitinib-resistant cell line PC9/GR. Furthermore, the study explored whether HOTAIR could modulate EGFR-TKIs resistance through the Hedgehog-GLi1 signaling pathway. The experimental results showed that sodium alginate (SA) microspheres demonstrated excellent biocompatibility with high encapsulation efficiency and drug-loading capacity, effectively enhancing the silencing efficiency of siRNA. HOTAIR siRNA significantly inhibited the proliferation, migration, and invasion abilities of PC9/GR cells while promoting apoptosis. Additionally, HOTAIR siRNA effectively suppressed tumor growth and downregulated the Hedgehog-GLi1 pathway and anti-apoptotic proteins, which were confirmed in animal experiments. Moreover, SA/HOTAIR siRNA exhibited superior inhibition of cellular and tumor functions compared to using HOTAIR siRNA alone. Clinical research findings indicated that monitoring the expression level of HOTAIR in the serum and urine samples of NSCLC patients before and after receiving EGFR-TKIs treatment can predict the efficacy of EGFR-TKIs to a certain extent. This study provided evidence that HOTAIR siRNA effectively mitigated the development of acquired resistance to EGFR-TKIs by inhibiting the Hedgehog-GLi1 pathway. Furthermore, it introduced a reliable and long-lasting drug delivery system for combating acquired resistance to EGFR-TKIs.

Complications of transcutaneous osseointegrated prosthetic systems (TOPS) focus on the metal-cutaneous interface at the stoma. Besides pain due to scare tissue as well as undefined neuropathic disorders, there is high evidence that the stoma presents the main risk causing hypergranulation and ascending infection. To restore the cutaneous barrier function in this functional area, soft-tissue on- or in-growth providing a vital and mechanically stable bio-artificial conjunction is considered a promising approach. In this study we assessed viability and proliferation of adult human dermal fibroblasts (HDFa) on modifications of a standard prosthetic titanium surface. Un-coated (TiAl6V4) as well as a titanium-nitrite (TiN) coated additive manufactured porous three-dimensional surface structures (EPORE®) were seeded with HDFa and compared to plain TiAl6V4 and polystyrene surfaces as control. Cell viability and proliferation were assessed at 24 h and 7 days after seeding with a fluorescence-based live-dead assay. Adhesion and cell morphology were analyzed by scanning electron microscopy at the respective measurements. Both EPORE® surface specifications revealed a homogenous cell distribution with flat and spread cell morphology forming filopodia at both measurements. Proliferation and trend to confluence was seen on un-coated EPORE® surfaces with ongoing incubation but appeared substantially lower on the TiN-coated EPORE® specification. While cell viability on both EPORE® specifications was comparable to plain TiAL6V4 and polystyrene controls, cell proliferation and confluence were less pronounced when compared to controls. The EPORE® topography allows for fibroblast adhesion and viability in both standard TiAl6V4 and - to a minor degree - TiN-coated specifications as a proof of principle.

In order to enhance the antibacterial property of titanium implant without inducing obvious cytotoxicity, the combination of Ag nanolayer and micro/nano surface structure was conducted by magnetron sputtering and hot-alkali treatment in this study. A series of specimens (AH-Ti, AH-Ti/Ag0.25, AH-Ti/Ag1, AH-Ti/Ag2, and AH-Ti/Ag5) were prepared with different sputtering durations (0 min, 0.25 min, 1 min, 2 min, 5 min), respectively, all realizing long-term release of Ag+. In vitro experiments indicated that AH-Ti/Ag1 group possessed good cytocompatibility, nice osteogenic ability, and excellent antibacterial efficiency as well. In addition, AH-Ti/Ag0.25 showed good biocompatibility, while the reduction of S.aureus (78.5%) was not enough compared with AH-Ti/Ag1. Although the AH-Ti/Ag2 and AH-Ti/Ag5 group showed superior antibacterial activity, their obvious cytotoxicity caused low ALP and mineralization level. Therefore, the design of suitable Ag nanolayer coating combined with micro/nano surface structure (AH-Ti/Ag1) might be a promising strategy to enhance osteogenic property and maintain excellent antibacterial ability at the same time.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245 nm indicating a high Ce⁺³/Ce⁺⁴ ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1 mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1 mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1 mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

In recent years, Ag nanoparticle (Ag NP)-loaded antibacterial dressings have attracted much attention in high-level medical dressings. However, the high cytotoxicity of Ag NP has always been a problem. In this paper, we examined the improvement of antibacterial activity of berberine hydrochloride (BBR) with Ag NP, the results showed that the combined use of BBR and Ag NP can effectively reduce the dosage of Ag NP while ensuring the inhibition of bacterial growth, thus an intermediate layer dressing containing combined drugs were prepared. At the same time, the top dressing of polyvinyl alcohol (PVA) solid film and the PVA bottom dressings with three kinds of leakage structures were prepared by 3D printing technology. Three kinds of PVA bottom dressings showed high quality consistency, and the greater the number of leak holes, the higher the porosity value of the dressing, while the swelling ratio value of the bottom layer dressing with three holes was the lowest. Finally, three types of BBR-Ag NP composite antibacterial dressings (3D-BBR-Ag NP) can be obtained by self-assembling of the top dressing, the intermediate layer dressing, and the bottom dressings with three kinds of leakage structures. The cumulative drug release results showed that dressing with more holes had a faster drug release rate compared to the other two ones with fewer leakage holes. Besides, five drug release kinetic models were used to investigate the cumulative BBR release profiles for three types of 3D-BBR-Ag NP. And the three types of composite dressings showed strong antibacterial activity after 6 h of cultivation with staphylococcus aureus. The study showed that the antibacterial activity of the self-assembled dressing prepared by combination of BBR with Ag NP can be improved, and the drug release rate of the hydrogel dressing can be flexibly controlled through 3D printing technology.

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1β; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-β1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

The high hydrophobicity and low oral availability of immunosuppressive drug, rapamycin, seriously limit its application. It was thus aimed to develop a PEG-PLGA based nano-loading system for rapamycin delivery to achieve improved bioavailability with sustained effects via a novel microfluidic chip and manipulation of the hydrophobic PLGA chain length. PDMS based microfluidic chip with Y shape was designed and PEG-PLGA polymers with different PLGA chain length were used to prepare rapamycin nano-delivery systems. Dendritic cells were selected to evaluate the immunosuppressive effect of the nanoparticles including cytotoxicity assay, dendritic cell activation, and cytokine levels. The effects of different PEG-PLGA nanoparticles on the immunomodulatory properties were finally compared. It was shown that PEG-PLGA could be successfully used for rapamycin encapsulation via microfluidics to obtain nano-delivery systems (Rapa&P-20 k, Rapa&P-50 k and Rapa&P-95 k) ranging from 100 nm to 116 nm. The encapsulation efficiency was ranged from 69.70% to 84.55% and drug loading from 10.45% to 12.68%. The Rapa&P-50 k (PLGA chain length: 50 k) could achieve the highest drug loading (DL) and encapsulation efficiency (EE) as 12.68% and 84.55%. The encapsulated rapamycin could be gradually released from three nanoparticles for more than 1 month without any noticeable burst release. The Rapa & P nanoparticles exhibited enhanced immunosuppressive effects over those of free rapamycin as shown by the expression of CD40 and CD80, and the secretion of IL-1β, IL-12 and TGF-β1. Rapa&P-50 k nanoparticles could be the optimal choice for rapamycin delivery as it also achieved the most effective immunosuppressive property. Hence, this study could provide an efficient technology with superior manipulation to offer a solution for rapamycin delivery and clinical application.

In tissue engineering, the development of an appropriate scaffold is crucial to provide a framework for new tissue growth. The use of cryogels as scaffolds shows promise due to their macroporous structure, but the pore size, distribution, and interconnectivity is highly variable depending on the fabrication process. The objective of the current research is to provide a technique for controlled anisotropy in chitosan-gelatin cryogels to develop scaffolds for bone tissue engineering application. A mold was developed using additive manufacturing to be used during the freezing process in order to fabricate cryogels with a more interconnected pore structure. The scaffolds were tested to evaluate their porosity, mechanical strength, and to observe cell infiltration through the cryogel. It was found that the use of the mold allowed for the creation of designated pores within the cryogel structure which facilitated cell infiltration to the center of the scaffold without sacrificing mechanical integrity of the structure.

The objective of this study was to coat negatively charged polymer brushes covalently onto the surface of thermoplastic polyurethane (TPU) using a simple conventional surface free-radical polymerization technique. The coated surfaces were assessed with contact angle, protein adsorption, cell adhesion and bacterial adhesion. Bovine serum albumin (BSA) and bovine fibrinogen (BFG) were used for protein adsorption evaluation. Mouse fibroblasts (NIH-3T3) and Pseudomonas aeruginosa (P. aeruginosa) were used to assess surface adhesion. Results show that the TPU surface modified with the attached polymer brushes exhibited significantly reduced contact angle, protein adsorption, and cell as well as bacterial adhesion, among which the negatively charged polymers showed the extremely low values in all the tests. Its contact angle is 5°, as compared to 70° for original TPU. Its BSA, BFG, 3T3 adhesion and P. aeruginosa adhesion were 93%, 84%, 92%, and 93% lower than original TPU. Furthermore, the TPU surface coated with negatively charged polymer brushes exhibited a hydrogel-like property. The results indicate that placing acrylic acids using a simple surface-initiated free-radical polymerization onto a TPU surface and then converting those to negative charges can be an effective and efficient route for fouling resistant applications.