Journal of Biomaterials Applications最新文献

A composite hemostatic sponge consisting of chitosan (CS) with oyster shell powder (OSP) has been developed as a potentially sustainable composite material for controlling hemorrhage at the injury site. The system is designed assuming that Ca⁺ released by OSP will accelerate the effect of chitosan at damage sites, enhancing the overall hemostatic efficacy. The sponge was thoroughly characterized using FTIR, SEM, and EDX analysis. In vitro, blood clotting assays such as clotting time (CT) [188 ± 4 s], prothrombin time (PT) [36 ± 1 s], activated partial thromboplastin time (aPTT) [51 ± 2 s], and plasma recalcification time (PRT) [58 ± 3 s] demonstrated that the inclusion of CaCO₃ significantly improved clot formation, with the CS-OSP sponge outperforming control sponges without OSP. RT-PCR analysis of vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor (PDGF), and interleukin growth factor 1 (IGF-1) on fibroblast cell lines evidenced the wound healing-promoting activity of OSP-reinforced CS sponges. This was further supported by in vivo studies using a rabbit femoral artery injury model, where the CaCO₃-enhanced sponge achieved superior hemostasis and reduced blood loss more effectively than the control sponges without CaCO₃. These findings suggest that the oyster shell-derived CaCO₃ enhances the hemostatic activity of chitosan-based sponges, providing a promising candidate for rapid hemorrhage control in clinical settings, particularly in scenarios involving both oozing and pressurized bleeding.

Firm soft tissue attachment on oral implant components together with good bacterial control are important prerequisites for uneventful implant healing. TiO₂ coatings have been shown to enhance human gingival fibroblast attachment, but the coating does not have antimicrobial properties. Phytosphingosine (PHS) is known to have antifouling properties against the cariogenic bacterium Streptococcus mutans (S. mutans) which is also among the first colonizers on implant surfaces. This makes PHS an interesting agent to prevent microbial adhesion on dental implant surfaces. The aim of this study was to examine the impact of PHS on S. mutans and human gingival fibroblast adhesion on titanium surfaces with or without TiO₂ -coating. Titanium discs (n = 99, diameter 14 mm, thickness 1 mm) were fabricated for the study. The discs were divided into four groups: (1) non-coated discs (NC), (2) titanium discs with hydrothermally induced TiO₂ coatings (HT), (3) NC discs treated with PHS solution and (4) HT discs treated with PHS solution. Hydrophilicity of the discs was evaluated by water contact angle measurement. S. mutans was added on HT and NC discs with or without PHS treatment for 30 minutes and the number of attached bacteria was estimated by plate counting method. For fibroblast experiment, the cells were plated on the discs and the number of adhered fibroblasts was determined at three time points (1, 3, 6 h). Additionally, confocal microscope images were obtained to examine fibroblast and S. mutans adhesion and to evaluate cell spreading. PHS treatment significantly decreased the hydrophilicity of HT and NC titanium surfaces (p < .001). S. mutans adhesion was significantly reduced after PHS treatment on both NC (p < .001) and HT surfaces (p < .001). Fibroblast adhesion was significantly reduced in HT group at 1 and 3h time points (p < .001), situation leveling out by the 6th hour. PHS reduced the number of adhered fibroblasts to the surface at incubation times of 1 hours (p = .0011) and 3 hours (p = .0194). At the 6 hour time point the number of adhered cells was no longer reduced, but still a reduction in cell spreading on the surface was observed (p < .05). The adhesion differences were present only in HT group. The PHS treatment reduced adherence of S. mutans and fibroblasts on TiO₂ coated titanium, which may result from reduced hydrophilicity of the surfaces. The dual approach of PHS treatment and TiO₂ coating could provide microbial antifouling properties of dental implants but may also affect fibroblast adhesion.

Fused deposition modeling (FDM) is emerging as a promising technique for manufacturing bioresorbable stents (BRS), particularly for coronary artery disease treatment. Polycaprolactone (PCL) has emerged as a favored material due to its biocompatibility, controlled degradation rate and mechanical properties. This review provides a comprehensive analysis of the effects of key FDM printing parameters on the quality aspects of PCL-based BRS, focusing on morphological, mechanical and biological characteristics. This review also highlights inconsistencies in previous studies, particularly in the impact of these parameters on stent dimensions and mechanical properties, emphasizing the need for standardization in experimental methodologies. Additionally, the current gaps in research related to the mechanical and biological performances of PCL-based BRS are discussed, with a call for further studies on long-term effects. This review aims to guide future research by offering insights into optimizing FDM parameters for improving the overall performance and clinical outcomes of PCL-based BRS.

A functional and biocompatible biomaterial is essential for accelerating the regeneration of skin tissue at the wound site. Hydrogel scaffolds in three dimensions show promising candidates for this purpose. This study was conducted to design a novel porous cross-linked alginate (Alg) hydrogel containing green tea (GT) and assess its morphology, swelling, weight loss, hemocompatibility, and cytocompatibility. Ultimately, the created hydrogel's therapeutic effectiveness was examined in a complete dermal diabetes wound model. The findings indicated that the hydrogel prepared had significant porosity, with interconnected pores around 75.821 µm in size. The weight loss evaluation indicated that the created hydrogel can be degraded naturally, with a weight loss ratio of about 74% for Alg/GT 80 mg after being incubated for 24 hours. Additionally, the study indicated that hydrogel dressings exhibited greater wound closure compared to gauze-treated wounds, which served as the control. The group with GT at a concentration of 80 mg showed the highest percentage of wound closure. The histopathological studies and IHC evaluation for TGF-β1 confirmed the in vivo finding. This study proposes utilizing 3D Alg hydrogels with GT as a wound dressing, but further studies are needed.

Peripheral nerve injuries are a major global health issue, with current treatments showing significant limitations. Neural tissue engineering provides a promising solution by creating supportive environments for nerve regeneration. This study used advanced 3D bioprinting to produce biomimetic scaffolds from graphene-enhanced bio-inks, integrating cells, scaffold materials, and growth signals. Compared to traditional methods, 3D printing ensures precise material distribution, improving cell density. The bio-ink, made of graphene (Gr), gelatin (Gel), and sodium alginate (SA), was tested at concentrations of 0.02%, 0.08%, and 0.2% to find the best formula for neural repair. Among four scaffold groups (Gel/SA, 0.02% Gr/Gel/SA, 0.08% Gr/Gel/SA, 0.2% Gr/Gel/SA), the 0.08% Gr scaffold showed the best mechanical strength, structural integrity, and biocompatibility. Graphene improved the scaffolds' compressive strength and degradation balance but reduced water absorption, porosity and increased the contact angle at higher concentrations. PC12 cells on the scaffolds showed excellent proliferation and minimal toxicity at lower graphene levels. The 0.08% Gr scaffold was most effective in nerve regeneration, highlighting the potential of graphene-enhanced 3D-printed scaffolds for neural tissue engineering. This research underscores the importance of 3D bioprinting in advancing nerve repair treatments.

To achieve successful bone tissue engineering (BTE), it is necessary to fabricate a biomedical scaffold with appropriate structure as well as favorable composition. Despite a broad range of studies, this remains a challenge, highlighting the need for a better understanding of how structural features (e.g., pore size) and scaffold composition influence mechanical and physical properties, as well as cellular behavior. Therefore, the objective of this study was to characterize physical properties (swelling, degradation), mechanical properties (compressive modulus), and cellular behavior in relation to varying compositions (referred to composite and hybrid scaffolds) as well as varying pore sizes in three-dimensional (3D) printed scaffolds. Composite scaffolds were fabricated from polycaprolactone (PCL) and two different graphene oxide (GO) (3% and 9% (w/v)) concentrations. Additionally, hybrid scaffolds were fabricated by impregnating 3D printed scaffolds in a hydrogel blend of alginate/gelatin. Pore sizes of 400, 1000, and 1500 μm were investigated in this study to assess their effect on the scaffold properties. Our findings showed that swelling and degradation properties were enhanced by (I) the addition of GO as well as introduction of both hydrogel and highest concentration of GO (9% (w/v) GO) into the polymeric matrix of PCL, and (II) increasing the pore size within the scaffolds. Mechanical testing revealed that compressive elastic modulus increased with decreasing pore size, incorporation of GO, and increasing GO content into the matrix of PCL. Although our investigated scaffolds with various pore sizes did not show comparable elastic moduli to that of cortical bone, they exhibited an elastic modulus range (∼31-48 MPa) matching that of trabecular bone. The highest compressive modulus (∼48 MPa) was observed in scaffolds of PCL/9% (w/v) GO (composite scaffolds) with the pore size of 400 μm. Cell viability assay demonstrated high MG-63 cell survival (greater than 70%) in all composite and hybrid scaffolds (indicating scaffold biocompatibility) except PCL/3% (w/v) GO scaffolds. The findings of this study contribute to the field of BTE by providing scaffold design insights in terms of pore size and composition.

EGFR is overexpressed in several cancers and hence EGFR-targeted theranostics is a promising approach to manage cancers, with widespread applicability. When nanoceria, which possesses intrinsic anticancer properties, is conjugated with EGFR-targeted fluorophore-tagged ligands, this nanoformulation can both image tumors and kill them through ROS-mediated cell destruction. Further, targeting enhances the cellular uptake of nanoparticles through EGFR-mediated endocytosis. The present work evaluates the in vitro theranostic performance of FITC-tagged EGF-functionalized nanoceria on EGFR-positive cancers. Three EGFR-positive cell lines were used for the study: MDA-MB-231, PANC-1 and HeLa. The EGFR-binding specificity of the EGF-functionalized nanoparticles was confirmed using western blot analysis. The therapeutic and diagnostic activities of the theranostic nanoparticles were confirmed, the former by cell viability assays and ROS measurements and the latter by confocal imaging. The results demonstrate significant ROS elevation levels for the treated cells and hence the suitability of the particles for therapeutic applications. The nanoparticles also are capable of detection using fluorescence imaging following 5 minutes of treatment, thus confirming the applicability for imaging. Hemolysis assay studies revealed excellent hemocompatibility of the nanoparticles, confirming their suitability for in vivo applications.

Early endothelialization and the prevention of platelet adhesion are crucial in the development of small-diameter vascular grafts to prevent thrombus formation and intimal thickening. Silk fibroin (SF) from Bombyx mori is commonly used for such grafts. In our previous study, we found that silk vascular grafts coated with sponge-like transgenic (TG) silk incorporating the arginine-glutamic acid-aspartate-valine (REDV) peptide and transplanted into rats yielded favorable results. In this study, we aimed to achieve even better results by incorporating additional peptides into TG silk containing REDV and coating silk vascular grafts with this sponge. Initially, we sought to identify such peptides. We attempted to immobilize several peptides containing REDV onto silk using cyanuric chloride. Cell culture experiments with normal human umbilical vein endothelial cells (HUVECs) were performed on SF, SF+REDV, SF + arginine-glycine- aspartate (RGD), SF+cysteine-alanine-glycine (CAG), and SF + isoleucine-lysine- valine- alanine-valine (IKVAV) films to assess adhesion, proliferation, and extensibility; SF+RGD and SF+IKVAV films demonstrated high adhesion behavior of HUVECs. In addition, platelet adhesion on these SF+peptide films was evaluated. Platelet adhesion strength was much higher on SF+RGD films than on other SF+peptide films. These results suggest that IKVAV may be the most suitable peptide for coating SF vascular grafts. Subsequently, we successfully produced TG silk incorporating IKVAV+REDV. We then coated small-diameter silk vascular grafts with sponge-like TG silk incorporating IKVAV+REDV and measured its physical properties.

Niches, which are combinations of extracellular matrix and cytokines, play essential roles in the stem cell biology. In this study, genipin stabilized fibrin microbeads (gFMBs) were prepared through oil emulsion method. Then, sonic hedgehog (SHH) was crosslinked to the surface of gFMBs by using genipin. These gFMBs were designated as gFMB@SHH since SHH was attached to their surface. Moreover, ectomesenchymal stem cells (EMSCs) were cultured, characterized, and used to test gFMB@SHH. Genipin not only changed the color of fibrin microbeads (FMBs) to deep blue, but also stabilized FMBs by delaying their degradation in vitro. In addition to the nontoxic and proliferation promoting effects of gFMB@SHH on EMSCs, gFMBs@SHH could induce neural differentiation of EMSCs by stimulating the SHH/Gli pathway. Therefore, genipin stabilized fibrin microbeads might be a promising structure to construct niches for in vitro stem cell researches.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, the poor hydrophilicity of most photosensitizers makes them difficult to enter the cells and also susceptible to aggregation-induced quenching in aqueous environment. In this study, we encapsulated protoporphyrin IX (PPIX) by nanostructured lipid carrier to obtain a water-soluble PPIX delivery system (NLC-PPIX). The nanoparticles exhibited high colloidal stability and good fluorescence emission. The generation of ¹O₂ from the NLC-PPIX was verified using 9,10-anthracenediyl-bis(methylene)dicarboxylic acid (ABDA) as ¹O₂ indicator. The ¹O₂ quantum yield of the NLC-PPIX in aqueous solution was calculated to be ∼9%. The flow cytometry and fluorescence imaging confirmed the uptake of NLC-PPIX by the A2058 cells and the generation of ¹O₂ inside the cells under light excitation. The in vitro cytotoxicity assay showed that the NLC-PPIX exerted no toxicity on the A2058 cells under dark conditions, while light irradiation triggered high phototoxicity. The cell viability of the A2058 cells was significantly decreased and the inhibition rate reached approximately 96% by treating the cells with 200 μg/mL NLC-PPIX and 420 nm light irradiation. The successful cancer cell uptake and PDT effect revealed the therapeutic promise of our drug delivery system.