Glass Scaffolds Research Articles

Processing and cytocompatibility of Cu-doped and undoped fluoride-containing bioactive glasses

Sintered or additive-manufactured bioactive glass (BG) scaffolds are highly interesting for bone replacement applications. However, crystallization often limits the high-temperature processability of bioactive glasses (BGs). Thus, the BG composition must combine high bioactivity and processability. In this study, three BGs with nominal molar (%) compositions 54.6SiO2-1.7P2O3-22.1CaO-6.0Na2O-7.9K2O-7.7MgO (13–93), 44.8SiO2-2.5P2O3-36.5CaO-6.6Na2O-6.6K2O-3.0CaF2 (F3) and 44.8SiO2-2.5P2O3-35.5CaO-6.6Na2O-6.6K2O-3.0CaF2-1.0CuO (F3–Cu) were investigated. The dissolution and ion release kinetics were investigated on milled glass powder and crystallized particles (500–600 μm). All glasses showed the precipitation of hydroxyapatite (HAp) crystals after 7 days of immersion in simulated body fluid. No significant differences in ion release from glass and crystalline samples were detected. The influence of surface roughness on cytocompatibility and growth of pre-osteoblast cells (MC3T3-E1) was investigated on sintered and polished BG pellets. Results showed that sintered BG pellets were cytocompatible, and cells were seen to be well attached and spread on the surface after 5 days of incubation. The results showed an inverse relation of cell viability with the surface roughness of pellets, and cells were seen to attach and spread along the direction of scratches.

Pore graded borosilicate bioactive glass scaffolds: in vitro dissolution and cytocompatibility

3D borosilicate bioactive glass (1393B20 and B12.5MgSr) scaffolds were prepared by robocasting, with and without a dense layer at the top. Pore graded scaffolds are promising as they allow for membrane deposition and could limit the risk of soft tissue infiltration. In vitro dissolution was studied in tris(hydroxymethyl)aminomethane (TRIS) and Simulated Body Fluid (SBF). 1393B20 scaffolds dissolved faster than B12.5MgSr in TRIS whereas they dissolved slower in SBF. The difference in dissolution profiles, as a function of the medium used, is assigned to the different rates of precipitation of hydroxyapatite (HA). While the precipitation of calcium phosphate (CaP) in the form of HA, first sign of bioactivity, was confirmed by ICP, FTIR-ATR and SEM-EDX analysis for both compositions, 1393B20 was found to precipitate HA at a faster rate. The presence of a dense top layer did not significantly impact the dissolution rate and CaP precipitation. In vitro cell culture was performed using human adipose-derived stem cells (hADSCs). Prior to cell plating, a preincubation of 3 days was found optimum to prevent burst ion release. In direct contact, cells proliferate and spread on the scaffolds while maintaining characteristic spindle morphology. Cell plated on 1393B20 scaffolds showed increased viability when compared to cell plated on B12.5MgSr. The lower cell viability, when testing B12.5MgSr, was assigned to the depletion of Ca2+ ions from culture medium and higher pH. Static cell culture leads to believe that the scaffold produced from the 1393B20 glass composition are promising in bone regeneration applications.Graphical

Apt‐19s‐Functionalized 3D‐Printed Mesoporous Bioactive Glass Scaffold Promotes BMSC Recruitment in Bone Regeneration via SDF‐1α/CXCR4 Axis and MAPK Signaling

AbstractDirectional migration and differentiation of stem cells in situ are two essential processes for tissue regeneration. However, transplanted scaffold itself lacks sufficient ability to induce stem cell recruitment. As an artificial synthesized nucleic acid, aptamer 19s (Apt‐19s), with high cost‐effectiveness and bioactivity, demonstrates a robust capacity for specific binding and recruitment of mesenchymal stem cells. In this study, a mesoporous bioactive glass scaffold fabricated via a seamless route of self‐assembly and 3D printing (3D‐MBG), functionalized with Apt‐19s is successfully prepared via physical adsorption and lyophilization with optimized release kinetics and bone marrow‐derived mesenchymal stem cells (BMSCs) recruiting efficiency in vitro. This scaffold significantly enhanced migration and osteogenic differentiation of BMSCs in vitro and in vivo. The mechanism underlying Apt‐19s‐induced BMSCs recruitment is elucidated for the first time, that Apt‐19s promoted BMSCs migration by upregulating stromal cell‐derived factor‐1α (SDF‐1α) gene expression, facilitating SDF‐1α protein translation and secretion, and further activating the SDF‐1α/CXCR4 signaling axis and MAPK pathway. In summary, the Apt‐19s‐functionalized 3D‐MBG scaffold offers an economical and efficient solution for customized bone regeneration in situ, and the elucidation of Apt‐19s‐induced BMSCs recruitment at molecular biological level may shed light on its broader clinical applications.

Preparation of trivalent rare-earth element-substituted bioactive glass robocast scaffolds for osteosarcoma treatment: structural, morphological, mechanical, drug delivery, and biological properties

In this study, trivalent rare-earth ion (Eu3+, Gd3+, and Yb3+)-substituted silicate-based bioactive glass scaffolds were prepared by robocasting method using sol–gel-derived bioactive glass powders for tissue engineering applications and cancer therapy. The structural, morphological, and mechanical properties of the prepared scaffolds as well as their in vitro bioactivity in simulated body fluid (SBF) were investigated in detail. In addition, an anticancer drug (5-FU) adsorption and release behavior of the scaffolds was studied as a function of time. In vitro, cytotoxicity and alkaline phosphatase activity were investigated using human skin fibroblast BJ and osteosarcoma SaOS-2 cells. Results showed that using lanthanide ion-containing (0.5, 1, 3, and 5 wt%) sol–gel-derived bioactive glass powders it was possible to successfully fabricate periodic, mesh-like patterned robocast glass scaffolds. All of the scaffolds prepared in the study sintered at 675 °C showed an amorphous structure. The compressive strength of scaffolds was in the range of 8.8 MPa to 13.6 MPa and the highest strength values were obtained in the Yb3+-containing scaffolds. Hydroxyapatite formation was obtained for the scaffolds immersed in SBF for 28 days. The fluorouracil adsorption amount was calculated to be ~ 25% for all types of scaffolds and the cumulative drug release was in the range of 20–25% depending on the dopant concentration. Results of the in vitro cell culture experiments revealed that all of the scaffolds fabricated in the study were not cytotoxic to fibroblast and osteosarcoma cells for up to 7 days under in vitro conditions. An increase was obtained for the ALP activities for both types of cells as the incubation time was increased.

Cell-free chitosan/silk fibroin/bioactive glass scaffolds with radial pore for in situ inductive regeneration of critical-size bone defects

Tissue-engineered is an effective method for repairing critical-size bone defects. The application of bioactive scaffold provides artificial matrix and suitable microenvironment for cell recruitment and extracellular matrix deposition, which can effectively accelerate the process of tissue regeneration. Among various scaffold properties, appropriate pore structure and distribution have been proven to play a crucial role in inducing cell infiltration differentiation and in-situ tissue regeneration. In this study, a chitosan (CS) /silk fibroin (SF) /bioactive glass (BG) composite scaffold with distinctive radially oriented pore structure was constructed. The composite scaffolds had stable physical and chemical properties, a unique pore structure of radial arrangement from the center to the periphery and excellent mechanical properties. In vitro biological studies indicated that the CS/SF/BG scaffold could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the expression of related genes due to the wide range of connected pore structures and released active elements. Furthermore, in vivo study showed CS/SF/BG scaffold with radial pores was more conducive to the repair of skull defects in rats with accelerated healing speed during the bone tissue remodeling process. These results demonstrated the developed CS/SF/BG scaffold would be a promising therapeutic strategy for the repair of bone defects regeneration.

Mesoporous bioactive glass scaffolds for the delivery of bone marrow stem cell-derived osteoinductive extracellular vesicles lncRNA promote senescent bone defect repair by targeting the miR-1843a-5p/Mob3a/YAP axis

Bone repair in elderly patients poses a huge challenge due to the age-related progressive decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Bioactive scaffolds have been applied in bone regeneration due to their various biological functions. In this study, we aimed to fabricate functionalized bioactive scaffolds through loading osteoinductive extracellular vesicles (OI-EVs) based on mesoporous bioactive glass (MBG) scaffolds (1010 particles/scaffold) and to investigate its effects on osteogenesis and senescence of BMSCs. The results suggested that OI-EVs upregulate the proliferative and osteogenic capacities of senescent BMSCs. More importantly, The results showed that loading OI-EVs into MBG scaffolds achieved better bone regeneration. Furthermore, OI-EVs and BMSCs RNAs bioinformatics analysis indicated that OI-EVs play roles through transporting pivotal lncRNA acting as a “sponge” to compete with Mob3a for miR-1843a-5p to promote YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. Collectively, these results suggested that the OI-EVs lncRNA ceRNA regulatory networks might be the key point for senescent osteogenesis. More importantly, the study indicated the feasibility of loading OI-EVs into scaffolds and provided novel insights into biomaterial design for facilitating bone regeneration in the treatment of senescent bone defects. Statement of significanceConstructing OI-EVs/MBG delivering system and verification of its bone regeneration enhancement in senescent defect repair.Aging bone repair poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of BMSCs. OI-EVs/MBG delivering system were expected as promising treatment for senescent bone repair, which could provide an effective strategy for bone regeneration in elderly patients.Clarification of potential OI-EVs lncRNA ceRNA regulatory mechanism in senescent bone regenerationOI-EVs play important roles through transferring lncRNA-ENSRNOG00000056625 sponging miR-1843a-5p that targeted Mob3a to activate YAP translocation into nucleus, ultimately alleviate senescence, promote proliferation and osteogenic differentiation in O-BMSCs, which provides theoretical basis for EVs-mediated therapy in future clinical works.

Additive Manufacturing of Iron Carbide Incorporated Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug Delivery Applications.

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.

Cytocompatible and osteoconductive silicon oxycarbide glass scaffolds 3D printed by DLP: a potential material for bone tissue regeneration.

Bone lesions affect individuals of different age groups, compromising their daily activities and potentially leading to prolonged morbidity. Over the years, new compositions and manufacturing technologies were developed to offer customized solutions to replace injured tissue and stimulate tissue regeneration. This work used digital light processing (DPL) technology for three-dimensional (3D) printing of porous structures using pre-ceramic polymer, followed by pyrolysis to obtain SiOC vitreous scaffolds. The SiOC scaffolds produced had an amorphous structure (compatible with glass) with an average porosity of 72.69% ± 0.99, an average hardness of 935.1 ± 71.0HV, and an average maximum flexural stress of 7.8 ± 1.0MPa, similar to cancellous bone tissue. The scaffolds were not cytotoxic and allowed adult stem cell adhesion, growth, and expansion. After treatment with osteoinductive medium, adult stem cells in the SiOC scaffolds differentiated to osteoblasts, assuming a tissue-like structure, with organization in multiple layers and production of a dense fibrous matrix rich in hydroxyapatite. The in vitro analyses supported the hypothesis that the SiOC scaffolds produced in this work were suitable for use as a bone substitute for treating critically sized lesions, with the potential to stimulate the gradual process of regeneration of the native tissue. The data obtained stimulate the continuity of studies with the SiOC scaffolds developed in this work, paving the way for evaluating safety and biological activity in vivo.

A COMPARATIVE STUDY OF THREE DIFFERENT BIOACTIVE GLASS SCAFFOLDS TAILORED FOR CARTILAGE TISSUE ENGINEERING

The regenerative capacity of hyaline cartilage is greatly limited. To prevent the onset of osteoarthritis, cartilage defects have to be properly treated. Cartilage, tissue engineered by mean of bioactive glass (BG) scaffolds presents a promising approach. Until now, conventional BGs have been used mostly for bone regeneration, as they are able to form a hydroxyapatite (HA) layer and are therefore, less suited for cartilage reconstruction. The aim of this study is to compare two BGs based on a novel BG composition tailored specifically for cartilage (CAR12N) and patented by us with conventional BG (BG1393) with a similar topology. The highly porous scaffolds consisting of 100% BG (CAR12N, CAR12N with low Ca2+/Mg2+ and BG1393) were characterized and dynamically seeded with primary porcine articular chondrocytes (pACs) or primary human mesenchymal stem cells (hMSCs) for up to 21 days. Subsequently, cell viability, DNA and glycosaminoglycan contents, cartilage-specific gene and protein expression were evaluated. The manufacturing process led to a comparable high (over 80%) porosity in all scaffold variants. Ion release and pH profiles confirmed bioactivity for them. After both, 7 and 21 days, more than 60% of the total surfaces of all three glass scaffold variants was densely colonized by cells with a vitality rate of more than 80%. The GAG content was significantly higher in BG1393 colonized with pACs. In general, the GAG content was higher in pAC colonized scaffolds in comparison to those seeded with hMSCs. The gene expression of cartilage-specific collagen type II, aggrecan, SOX9 and FOXO1 could be detected in all scaffold variants, irrespectively whether seeded with pACs or hMSCs. Cartilage-specific ECM components could also be detected at the protein level. In conclusion, all three BGs allow the maintenance of the chondrogenic phenotype or chondrogenic differentiation of hMSCs and thus, they present a high potential for cartilage regeneration.

Bone tissue regeneration by 58S bioactive glass scaffolds containing exosome: an in vivo study.

Exosomes, the naturally secreted nanocarriers of cells, have recently been demonstrated to have therapeutic benefits in a variety of disease models where parent cells are not present. However, the use of exosomes in bone defect regeneration has been unusual, and little is documented about the underlying processes. In recent study we produced and characterized exosomes derived human endometrial mesenchymal stem stromal cells and 58S bioactive glass scaffolds; in following, in this research exosome loaded scaffolds synthetized and release of exosome, porosity and bioactivity of them were assessed. More over the effect of scaffolds on repair of critical-size bone defects in rat's calvaria was evaluated by histological examination and micro computed tomography (µ CT). The findings confirmed that constructed porous scaffolds consistently release exosomes; additionally, in vivo findings including Hematoxilin & Eosin staining, Immunohistochemistry, Masson's trichrome, histomorphometric analysis, and µ CT clarified that our implant has osteogenic properties. We discovered that Exo-treated scaffolds might promote osteogenesis especially compared to pure scaffolds, indicating that produced scaffolds containing exosomes could be a potential replacement in bone tissue engineering.

Enhancing Osteoblastic Cell Cultures with Gelatin Methacryloyl, Bovine Lactoferrin, and Bioactive Mesoporous Glass Scaffolds Loaded with Distinct Parsley Extracts.

The increasing interest in innovative solutions for addressing bone defects has driven research into the use of Bioactive Mesoporous Glasses (MBGs). These materials, distinguished by their well-ordered mesoporous structure, possess the capability to accommodate plant extracts with well-established osteogenic properties, including bovine lactoferrin (bLF), as part of their 3D scaffold composition. This harmonizes seamlessly with the ongoing advancements in the field of biomedicine. In this study, we fabricated 3D scaffolds utilizing MBGs loaded with extracts from parsley leaves (PL) and embryogenic cultures (EC), rich in bioactive compounds such as apigenin and kaempferol, which hold potential benefits for bone metabolism. Gelatin Methacryloyl (GelMa) served as the polymer, and bLF was included in the formulation. Cytocompatibility, Runx2 gene expression, ALP enzyme activity, and biomineralization were assessed in preosteoblastic MC3T3-E1 cell cultures. MBGs effectively integrated PL and EC extracts with loadings between 22.6 ± 0.1 and 43.6 ± 0.3 µM for PL and 26.3 ± 0.3 and 46.8 ± 0.4 µM for EC, ensuring cell viability through a release percentage between 28.3% and 59.9%. The incorporation of bLF in the 3D scaffold formulation showed significant differences compared to the control in all assays, even at concentrations below 0.2 µM. Combinations, especially PL + bLF at 0.19 µM, demonstrated additive potential, with superior biomineralization compared to EC. In summary, this study highlights the effectiveness of MBGs in incorporating PL and EC extracts, along with bLF, into 3D scaffolds. The results underscore cytocompatibility, osteogenic activity, and biomineralization, offering exciting potential for future in vivo applications.

Fabrication and characterizations of simvastatin-containing mesoporous bioactive glass and molybdenum disulfide scaffold for bone tissue engineering.

Due to the limitations of the current treatment approaches of allograft and autograft techniques, treating bone disorders is a significant challenge. To address these shortcomings, a novel biomaterial composite is required. This study presents the preparation and fabrication of a novel biomaterial composite scaffold that combines poly (D, L-lactide-co-glycolide) (PLGA), mesoporous bioactive glass (MBG), molybdenum disulfide (MoS2), and simvastatin (Sim) to address the limitations of current bone grafting techniques of autograft and allograft. The fabricated scaffold of PLGA-MBG-MoS2-Sim composites was developed using a low-cost hydraulic press and salt leaching method, and scanning electron microscopy (SEM) analysis confirmed the scaffolds have a pore size between 143 and 240 μm. The protein adsorption for fabricated scaffolds was increased at 24 h. The water adsorption and retention studies showed significant results on the PLGA-MBG-MoS2-Sim composite scaffold. The biodegradation studies of the PLGA-MBG-MoS2-Sim composite scaffold have shown 54% after 28 days. In vitro, bioactivity evaluation utilizing simulated body fluid studies confirmed the development of bone mineral hydroxyapatite on the scaffolds, which was characterized using x-ray diffraction, Fourier transform infrared, and SEM analysis. Furthermore, the PLGA-MBG-MoS2-Sim composite scaffold is biocompatible with C3H10T1/2 cells and expresses more alkaline phosphatase and mineralization activity. Additionally, in vivo research showed that PLGA-MBG-MoS2-Sim stimulates a higher rate of bone regeneration. These findings highlight the fabricated PLGA-MBG-MoS2-Sim composite scaffold presents a promising solution for the limitations of current bone grafting techniques.

IOX1 epigenetically enhanced photothermal therapy of 3D-printing silicene scaffolds against osteosarcoma with favorable bone regeneration

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions. Although photothermal therapy (PTT) has aroused expanding interest, characterizing negligible invasiveness and high spatiotemporal adjustment, few studies discussed its drawbacks, such as thermal injury to adjacent normal tissue and exceeded laser power density, implying that focusing on sensitizing OS to PTT instead of simply elevating the laser power density may be a fresh way to enhance the PTT efficacy and attenuate the side/adverse effects. Herein, we successfully constructed 3D-printing silicene bioactive glass scaffolds with preferable PTT efficacy at the second near-infrared (NIR-II) biowindow and outstanding osteogenic biofunctions owing to the release of bioactive elements during degradation. Impressively, a histone demethylase inhibitor, IOX1, was introduced before PTT to sensitize OS to thermal therapy and minimize the side/adverse effects. This work offered a distinctive paradigm for optimizing the PTT efficacy of osteogenic scaffolds against OS with epigenetic modulation agents.

Chitosan bioactive glass scaffolds for in vivo subcutaneous implantation, toxicity assessment, and diabetic wound healing upon animal model

This study aims to develop chitosan-bioactive glass (BG) scaffolds for diabetic wound healing, toxicity valuation, and subcutaneous implantation in animals for biocompatibility assessment. The scaffolds were prepared by lyophilization technique. In specific BG without sodium (Na), composited with chitosan for better biological activities. The equipped scaffolds were studied for their physiochemical, biological, in vitro and in vivo performances. The chitosan and chitosan-BG (Na free) scaffolds show reliable biocompatibility, cytocompatibility, anti-oxidant, and tissue regeneration. The biocompatibility, toxicity assessments, and diabetic skin wound healing experiments were examined through in vivo studies using Sprague Dawley rats. The extracted tissue samples were analyzed using hematoxylin-eosin- (H and E) and Masson's trichrome staining. Further, tissue excised after scaffold implantation declared non-toxic, non-allergic, and anti-inflammatory nature of chitosan scaffolds. Moreover, the total ribonucleic acid (RNA) expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) for the scaffolds against vascular endothelial growth factor (VEGF), and collagen type one (Col-1) primers. Admirably, the scaffolds achieved the best level of skin wound healing via tissue regeneration by increasing epithetical cell formation and collagen deposition. Thus, the biocompatibility, non-toxicity, anti-inflammatory, and wound healing efficiency proved that the chitosan-BG (Na free) scaffold can be readily substantial for wound healing.

Rapidly derived equimolar Ca: P phasic bioactive glass infused flexible gelatin multi-functional scaffolds – A promising tissue engineering

The study aims to design and fabricate an ultra-easier multi-functional biomedical polymeric scaffold loaded with unique equimolar Ca:P phasic bioactive glass material (BG). Gelatin (G) – 45S5 bioactive glass (BG) scaffolds were synthesized via a simple laboratory refrigerator with higher biocompatibility and cytocompatibility. The results proved that BG has enhanced bio-mineralization of the scaffolds and results support that the G: BG (1:2) ratio is the more appropriate composition. Brunauer-Emmett-Teller (BET) study confirms the higher surface area for pure Gelatin and G: BG (1:2). Scanning Electron Microscopic images display the precipitation of hydroxycarbonate apatite layer over the scaffolds on immersing it in simulated body fluid. Alkaline phosphate activity proved that G: BG (1:2) scaffold could induce mitogenesis in MG-63 osteoblast cells, thus helping in hard tissue regeneration. Sirius red collagen deposition showed that higher content bioactive glass incorporated Gelatin polymeric scaffold G: BG (1:2) could induce rapid collagen secretion of NIH 3T3 fibroblast cell line that could help in soft tissue regeneration and earlier wound healing. The scaffolds were also tested for cell viability using NIH 3T3 fibroblast cell lines and MG 63 osteoblastic cell lines through methyl thiazolyl tetrazolium (MTT) assay. Thus, the study shows a scaffold of appropriate composition G: BG (1:2) can be a multifunctional material to regenerate hard and soft tissues.

Chargeable persistent luminescence 3D-printed scaffolds: A stepwise tactic for osteosarcoma treatment

Osteosarcoma is the most frequent malignant primary bone tumor with a poor prognosis and remains a significant issue in clinics due to the unrepairable bone defect following surgery and the lingering tumor cells. Photodynamic therapy (PDT) with its non-invasive nature and spatiotemporally controllable feature exhibits specific therapeutic efficiency, but it is limited by phototoxicity caused by prolonged laser exposure. Herein, we design and engineer an irradiation-free bifunctional PDT scaffold (BG@SAO-RB) by integrating persistent luminescence material (SrAl2O4:Eu, Dy) and photosensitizer (rose bengal) into a 3D-printed bioactive glass scaffold for stepwise osteosarcoma elimination and bone defect repair. Owing to the design of a rechargeable internal light source, the constructed scaffolds with reactive oxygen species generation ability attain long-term and efficient PDT for osteosarcoma, leading to tumor cell killing and proliferative inhibition. The findings from tumor growth characteristics and pathological sections also confirm that BG@SAO-RB scaffolds achieve successful osteosarcoma ablation through long-term PDT in tumor-bearing nude mice. Notably, the as-designed scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells and accelerate bone regeneration, which was evidenced by the improved radiological and histological manifestations. This work broadens the biomedical application of persistent luminescence materials and implicates an efficient treatment paradigm for osteosarcoma elimination and subsequent bone tissue regeneration.

Three-dimensional glass scaffolds improve the In Vitro maturation of porcine cumulus-oocyte complexes and subsequent embryonic development after parthenogenetic activation

In vitro maturation (IVM) methods for porcine oocytes are still deficient in achieving full developmental capacity, as the currently available oocyte in vitro culture systems still have limitations. In vitro embryo production must also improve the porcine oocyte IVM system to acquire oocytes with good developmental potential. Herein, we tested a three-dimensional (3D) glass scaffold culture system for porcine oocyte maturation. After 42 h, we matured porcine cumulus-oocyte complexes (COCs) on either two-dimensional glass dishes (2D-B), two-dimensional microdrops (2D-W), or 3D glass scaffolds. The 3D glass scaffolds were tested for porcine oocyte maturation and embryonic development. Among these culture methods, the extended morphology of the 3D group maintained a 3D structure better than the 2D-B and 2D-W groups, which had flat COCs that grew close to the bottom of the culture vessel. The COCs of the 3D group had a higher cumulus expansion index and higher first polar body extrusion rate, cleavage rate, and blastocyst rate of parthenogenetic embryos than the 2D-B group. In the 3D group, the cumulus-expansion-related gene HAS2 and anti-apoptotic gene Bcl-2 were significantly upregulated (p < 0.05), while the pro-apoptotic gene Caspase3 was significantly downregulated (p < 0.05). The blastocysts of the 3D group had a higher relative expression of Bcl-2, Oct4, and Nanog than the other two groups (p < 0.05). The 3D group also had a more uniform distribution of mitochondrial membrane potential and mitochondria (p < 0.05), and its cytoplasmic active oxygen species content was much lower than that in the 2D-B group (p < 0.05). These results show that 3D glass scaffolds dramatically increased porcine oocyte maturation and embryonic development after parthenogenetic activation, providing a suitable culture model for porcine oocytes.

Influence of polylactide coating stereochemistry on mechanical and in vitro degradation properties of porous bioactive glass scaffolds for bone regeneration.

The mechanical properties of polylactide stereocomplexes (PLA SC) have been primarily studied through tensile testing, with inconsistent results, and the compressive properties of PLA SC compared to homocrystalline or amorphous PLA remain poorly understood. In this study, we coated porous bioactive glass 13-93 scaffolds with amorphous, homocrystalline, or stereocomplex PLA to investigate their mechanical and degradation properties before and after immersion in simulated body fluid. The glass scaffolds had interconnected pores and an average porosity of 76%. The PLA coatings, which were 10-100 μm thick and approximately 3% of the glass scaffold mass, covered the glass to a large extent. The compressive strength and toughness of all PLA-coated scaffolds were significantly higher than those of uncoated scaffolds, with approximately a fourfold increase before immersion and a twofold increase after immersion. The compressive strength and toughness of PLA SC-coated scaffolds were similar to those of scaffolds with homocrystalline PLA coating, and significantly higher than for scaffolds with amorphous PLA coating. All PLA coatings moderated the initial pH increase caused by the glass, which could benefit surrounding cells and bone tissue in vivo after implantation.

Self‐Adaptive MoO3−xSubnanometric Wires Incorporated Scaffolds for Osteosarcoma Therapy and Bone Regeneration

AbstractResidual tumor cells and bone tissue defects are two critical challenges in clinical osteosarcoma treatment. Herein, a subnanomedicine concept is proposed by developing a self‐adaptive functional tissue engineering scaffold constructed by integrating MoO3−xsubnanometric wires onto 3D printing bioactive glass scaffolds. The MoO3−xsubnanometric wires are synthesized by a one‐pot hydrothermal method, which aggregate in an acidic tumor microenvironment and react with hydrogen peroxide to produce reactive oxygen species for specific chemodynamic therapy. However, they can degrade rapidly under physiological conditions without causing toxicity. Moreover, self‐adaptively enhanced photothermal conversion enables tumor‐targeting photothermal therapy while enhancing chemodynamic therapy. Additionally, the Mo5+‐Mo6+transition enables lipid peroxide accumulation and glutathione depletion, thereby resulting in the deactivation of glutathione peroxidase 4 protein and ferroptosis through Western blot analysis, confocal laser scanning microscopy observation, and mRNA transcriptome analysis. In addition to its robustness against osteosarcoma, the constructed scaffolds can stimulate rat bone mesenchymal stem cell differentiation and proliferation as well as promote osteogenesis in bone defects. Therefore, this multifunctional scaffold not only validates the subnanomedicine concept but also provides a promising clinical strategy for bone tissue engineering.

Fabrication and characterization of novel multifunctional superparamagnetic and fluorescent bioactive glasses for biomedical applications

Magnetic-fluorescent nanosystems have wide applications in the biomedical field due to their dual ability of unique biomolecular fluorescent recognition and magnetic modes. In this study fabrication of superparamagnetic-fluorescent bioactive glasses in the form of particle, nanofiber, and 3D scaffold was performed by the inclusion of maghemite (γ-Fe2O3) nanoparticle and photoluminescent rare earth element ions (Eu3+, Gd3+, and Yb3+). Bioactive glasses in the form of particle, nanofiber, and 3D scaffolds were manufactured using sol-gel, electrospinning, and robocasting techniques, respectively. Morphological, structural, magnetic, and luminescence properties of the fabricated bioactive glasses have been investigated comprehensively using electron microscopy, x-ray diffractometer, vibrating sample magnetometer, Fourier transform infrared, and fluorescence spectrometers. The compressive strength of the robocast 3D glass scaffolds was measured. In vitro hydroxyapatite deposition on the surface of the bioactive glasses soaked in simulated body fluid for various times up to 28 days was also examined. Results showed that all of the bioactive glasses prepared in the study with different morphological characteristics have superparamagnetic properties. Saturation magnetization (Ms) values of the glasses were in the range of 7.20–12.50 emu/g. Additionally, all of the studied glass samples showed fluorescence behavior. The highest photoluminescence emission peak intensity was recorded for the Eu3+-doped robocast 3D glass scaffolds which is followed by nanofibrous and particulate forms of bioactive glass. Results of the in vitro bioactivity experiments showed that hydroxyapatite formation occurred on all of the bioactive glass samples and the highest hydroxyapatite formation rates were obtained for the fibrous glass samples due to their higher surface area.