Bone formation by Irisin-Poly vinyl alchol modified bioglass ceramic beads in the rabbit model.

In the aging society, slow bone regeneration poses a serious hindrance to the quality of life. To deal with this problem, in this study, we have combined irisin with the bioglass regular beads to enhance the bone regeneration process. For this purpose, highly porous bioglass was obtained as spherical beads by using sodium alginate. The bioglass was evaluated by various analytical techniques such as SEM, EDS, XRD, and pore size distribution. The results depicted that porous bioglass was prepared correctly and SEM analysis showed a highly porous bioglass was formulated. On this bioglass, irisin was loaded with the assistance of polyvinyl alcohol (PVA) in three concentrations (50 ng/ml, 100 ng/ml, and 150 ng/ml per 1 g of bioglass). SEM analysis showed that pores are covered with PVA. The irisin release profile showed a sustained release over the time period of 7 days. In vitro, biocompatibility evaluation by the MC3T3E1 cells showed that prepared bioglass and irisin loaded bioglass (BGI50, BGI100, and BG150) are highly biocompatible. Alizarin Red staining analysis showed that after 2 weeks BGI50 samples showed highest calcium nodule formation. In vivo in the rabbit femur model was conducted for 1 and 2 months. BGI150 samples showed highest BV/TV ratio of 37.1 after 2 months. The histological data showed new bone formation surrounding the beads and with beads loaded with irisin. Immunohistochemistry using markers OPN, RUNX, COL, and ALP supported the osteogenic properties of the irisin-loaded bioglass beads. The results indicated that irisin-loaded bioglass displayed remarkable bone regeneration.

Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia.

Despite the significant progress made in recent years, clinical issues with small-diameter vascular grafts related to low mechanical strength, thrombosis, intimal hyperplasia, and insufficient endothelialization remain unresolved. This study aims to design and fabricate a core-shell fibrous small-diameter vascular graft by co-axial electrospinning process, which will mechanically and biologically meet the benchmarks for blood vessel replacement. The presented graft (PGHV) comprised polycaprolactone/gelatin (shell) loaded with heparin-VEGF and polycaprolactone (core). This study hypothesized that the shell structure of the fibers would allow rapid degradation to release heparin-VEGF, and the core would provide mechanical strength for long-term application. Physico-mechanical evaluation, in vitro biocompatibility, and hemocompatibility assays were performed to ensure safe in vivo applications. After 25 days, the PGHV group released 79.47 ± 1.54% of heparin and 86.25 ± 1.19% of VEGF, and degradation of the shell was observed but the core remained pristine. Both the control (PG) and PGHV groups demonstrated robust mechanical properties. The PGHV group showed excellent biocompatibility and hemocompatibility compared to the PG group. After four months of rat aorta implantation, PGHV exhibited smooth muscle cell regeneration and complete endothelialization with a patency rate of 100%. The novel core-shell structured graft could be pivotal in vascular tissue regeneration application.

Evaluation of Gelatin/Hyaluronic Acid-Generated Bridging in a 3D-Printed Titanium Cage for Bone Regeneration.

3D-printed titanium (Ti) cages present an attractive alternative for addressing issues related to osteoporosis-induced fractures, accidental fractures, and spinal fusion surgery due to disc herniation. These Ti-based bone implants possess superior strength compared to other metals, allowing for versatile applications in orthopedic scenarios. However, when used as standalone solutions, certain considerations may arise, such as interaction with soft tissues. Therefore, to overcome these issues, the combination with hydrogel has been considered. In this study, to impart Ti with regenerative abilities a 3D-printed Ti cage was loaded with gelatin and hyaluronic acid (G-H) to improve the cell attachment ability of the Ti-based bone implants. The void spaces within the mesh structure of the 3D Ti cage were filled with G-H, creating a network of micro-sized pores. The filled G-H acted as the bridge for the cells to migrate toward the large inner pores of the 3D Ti cage. Due to the microporous surface and slow release of gelatin and hyaluronic acid, the biocompatibility of the coated Ti cage was increased with an elevation in osteoconduction as depicted by the up-regulation of bone-related gene expressions. The in vivo implantation in the rabbit femur model showed enhanced bone regeneration due to the coated G-H on the Ti cage compared to the pristine hollow Ti cage. The G-H filled the large holes of the 3D Ti cage that acted as a bridge for the cells to travel inside the implant and aided in the fast regeneration of bone.

Physico-biological and in vivo evaluation of irisin loaded 45S5 porous bioglass granules for bone regeneration.

In this study, we investigated the physico-biological and in-vivo evaluation of irisin loaded 45S5 bioglass bone graft for enhancing osteoblastic differentiation and bone regeneration in rat femur head defect model. Highly porous structure was obtained in the bioglass by burn-out process with varying the concentration of poly (methyl methacrylate) (PMMA) spheres. 10 % polyvinyl alcohol (PVA) was used as a binder for the sustain releasing of irisin on porous bioglass. Different concentrations of irisin were loaded on the selected bioglass samples and these were further evaluated for the biocompatibility and osteoblastic differentiation properties. The in vitro results demonstrated not only its biocompatibility but also that it stimulated pre-osteoblast differentiation. The in vivo data showed new bone formation as well as expression of osteogenic proteins like alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and collagen-1 (Col-1). Our results support the use of irisin loaded bioglass for the use of early bone regeneration.

In-vivo bone remodeling potential of Sr-d-Ca-P /PLLA-HAp coated biodegradable ZK60 alloy bone plate.

Magnesium and its alloys are widely applied biomaterials due to their biodegradability and biocompatibility. However, rapid degradation and hydrogen gas evolution hinder its applicability on a commercial scale. In this study, we developed an Mg alloy bone plate for bone remodeling and support after a fracture. We further coated the Mg alloy plate with Sr-D-Ca-P (Sr dopped Ca-P coating) and Sr-D-Ca-P/PLLA-HAp to evaluate and compare their biodegradability and biocompatibility in both in vitro and in vivo experiments. Chemical immersion and dip coating were employed for the formation of Sr-D-Ca-P and PLLA-HAp layers, respectively. In vitro evaluation depicted that both coatings delayed the degradation process and exhibited excellent biocompatibility. MC3T3-E1cells proliferation and osteogenic markers expression were also promoted. In vivo results showed that both Sr-D-Ca-P and Sr-D-Ca-P/PLLA-HAp coated bone plates had slower degradation rate as compared to Mg alloy. Remarkable bone remodeling was observed around the Sr-D-Ca-P/PLLA-HAp coated bone plate than bare Mg alloy and Sr-D-Ca-P coated bone plate. These results suggest that Sr-D-Ca-P/PLLA-HAp coated Mg alloy bone plate with lower degradation and enhanced biocompatibility can be applied as an orthopedic implant.

Photoelectrochemical approaches for the conversion of lignin at room temperature.

The selective cleavage of C-C/C-O linkages represents a key step toward achieving the chemical conversion of biomass to targeted value-added chemical products under ambient conditions. Using photoelectrosynthetic solar cells is a promising method to address the energy intensive depolymerization of lignin for the production of biofuels and valuable chemicals. This feature article gives an in-depth overview of recent progress using dye-sensitized photoelectrosynthetic solar cells (DSPECs) to initiate the cleavage of C-C/C-O bonds in lignin and related model compounds. This approach takes advantage of N-oxyl mediated catalysis in organic electrolytes and presents a promising direction for the sustainable production of chemicals currently derived from fossil fuels.

Physico-biological evaluation of 3D printed dECM/TOCN/alginate hydrogel based scaffolds for cartilage tissue regeneration.

Cartilage damage is the leading cause of osteoarthritis (OA), especially in an aging society. Mimicking the native cartilage microenvironment for chondrogenic differentiation along with constructing a stable and controlled architectural scaffold is considerably challenging. In this study, three-dimensional (3D) printed scaffolds using tempo-oxidized cellulose nanofiber (TOCN), decellularized extracellular matrix (dECM), and sodium alginate (SA) were fabricated for cartilage tissue regeneration. We prepared three groups (dECM80, dECM50, dECM20) of 3D printable hydrogels with different ratios of TOCN and dECM where SA concentration remained the same. Two-step crosslinking was performed with CaCl2 solution to achieve the highly stable 3D printed scaffolds. Finally, the fundamental physical characterizations showed that increasing the ratio of TOCN with dECM significantly improved the viscoelastic behaviour, stability, mechanical properties, and printability of the scaffolds. Based on the results, the 3D printed dECM50 scaffolds with controlled and identical pore sizes increased the whole-layer integrity and nutrient supply in each layer of the scaffold. Furthermore, evaluation of in vitro and in vivo biocompatibility of the scaffolds with rBMSCs indicated that dECM50 scaffolds provided a suitable microenvironment for cell proliferation and promoted chondrogenesis by remarkably expressing the cartilage-specific markers. This study demonstrates that 3D printed dECM50 scaffolds provide a favourable and promising microenvironment for cartilage tissue regeneration.

Effect of Co-culture of mesenchymal stem cell and glomerulus endothelial cell to promote endothelialization under optimized perfusion flow rate in whole renal ECM scaffold.

In recent era, many researches on implantable bio-artificial organs has been increased owing to large gap between donors and receivers. Comprehensive organ based researches on perfusion culture for cell injury using different flow rate have not been conducted at the cellular level. The present study investigated the co-culture of rat glomerulus endothelial cell (rGEC) and rat bone marrow mesenchymal stem cells (rBMSC) to develop micro vascularization in the kidney scaffolds culturing by bioreactor system. To obtain kidney scaffold, extracted rat kidneys were decellularized by 1% sodium dodecyl sulfate (SDS), 1% triton X-100, and distilled water. Expanded rGECs were injected through decellularized kidney scaffold artery and cultured using bioreactor system. Vascular endothelial cells adhered and proliferated on the renal ECM scaffold in the bioreactor system for 3, 7 and 14 days. Static, 1 â€‹ml/min and 2 â€‹ml/min flow rates (FR) were tested and among them, 1 â€‹ml/min flow rate was selected based on cell viability, glomerulus character, inflammation/endothelialization proteins expression level. However, the flow injury was still existed on primary cell cultured at vessel in kidney scaffold. Therefore, co-culture of rGEC â€‹+ â€‹rBMSC found suitable to possibly solve this problem and resulted increased cell proliferation and micro-vascularization in the glomerulus, reducing inflammation and cell death which induced by flow injury. The optimized perfusion rate under rGEC â€‹+ â€‹rBMSC co-culture conditions resulted in enhanced endocellularization to make ECM derived implantable renal scaffold and might be useful as a way of treatment of the acute renal failure.

Injectable demineralized bone matrix particles and their hydrogel bone grafts loaded with ß-tricalcium phosphate powder and granules: A comparative study.

Demineralized bone matrix (DBM), has been used as a bone-graft material because of its osteoconductivity and osteoinductivity. However, the previous research report that supports the single use of DBM is limited by its rapid resorption caused by the lack of calcium and phosphate. ß-Tricalcium phosphate (TCP) is an enriched calcium phosphate material suitable for bone healing with osteoconductive properties. In this study, we have developed injectable bone graft by the loading two kinds of TCP in DBM particles and thermo-sensitive DBM-derived hydrogel (hDBM). TCP powder (pTCP) and TCP granules (gTCP) were loaded into hDBM and DBM, respectively. The bone formation effect was investigated according to the morphological features of TCP. Residual growth factor concentrations were investigated; microstructure and morphology were characterized by SEM. In-vitro studies showed that hDBM/DBM/pTCP and hDBM/DBM/gTCP bone grafts were biocompatible and could promote osteogenesis by up-regulating the expression of Runx2 and OPN, bone-related genes. In-vivo studies using the rabbit-femur defect model revealed that the implanted hDBM/DBM/pTCP bone graft showed similar histology to that of fibrous dysplasia with the expression of CD68, whereas hDBM/DBM/gTCP showed good bone formation. Loading of gTCP in place of pTCP was noticed as an effective way to improve bone regeneration in an injectable hDBM/DBM hydrogel-based bone graft.

Liver tissue-derived ECM loaded nanocellulose-alginate-TCP composite beads for accelerated bone regeneration.

Guided bone regeneration with osteoinductive scaffolds is a competitive edge of tissue engineering due to faster and more consistent healing. In the present study, we developed such composite beads with nanocellulose reinforced alginate hydrogel that carriedß-tricalcium phosphate (ß-TCP) nano-powder and liver-derived extracellular matrix (ECM) from porcine. Interestingly, it was observed that the beads' group containing ECM-ß-TCP-alginate-nanocellulose (ETAC) was more cytocompatible than the others comprised ofß-TCP-alginate-nanocellulose (TAC) and alginate-nanocellulose (AC). Cell attachment on ETAC beads was dramatically increased with time. In parallel within vitroresults, ETAC beads produced uniform cortical and cancellous bone in the femur defect model of rabbits within 2 months. Although the group TAC also produced noticeable bone in the defect site, the healing quality was improved and regeneration was faster after adding ECM. This conclusion was not only confirmed by micro-anatomical analysis but also demonstrated with x-ray microtomography. In addition, the characteristic moldable and injectable properties made ETAC a promising scaffold for clinical applications.

Tailored alginate/PCL-gelatin-ß-TCP membrane for guided bone regeneration.

Membranes prepared for guided bone regeneration (GBR) signify valued resources, inhibiting fibrosis and assisting bone regenration. However, existing membranes lack bone regenerative capacity or adequate degradation profile. An alginate-casted polycaprolactone-gelatin-ß-tricalcium phosphate dual membrane was fabricated by electrospinning and casting processes to enhance new bone formation under a GBR process. Porous membranes were synthesized with suitable hydrophilicity, swelling, and degradation behavior to confirm the compatibility of the product in the body. Furthermore, osteoblast-type cell toxicity and cell adhesion results showed that the electrospun membrane offered compatible environment to cells while the alginate sheet was found capable enough to supress the cellular attachment, but was a non-toxic material. Post-implantation, thein-vivooutcomes of the dual-layered membrane, showed appreciable bone formation. Significantly, osteoid islands had fused in the membrane group by eight weeks. The infiltration of fibrous tissues was blocked by the alginate membrane, and the ingrowth of new bone was enhanced. Immunocytochemical analysis indicated that the dual membrane could direct more proteins which control mineralization and convene osteoconductive properties of tissue-engineered bone grafts.

Autologous stromal vascular fraction-loaded hyaluronic acid/gelatin-biphasic calcium phosphate scaffold for bone tissue regeneration.

Bone defect augmentation with synthetic materials is crucial due to the unavoidable limitations of auto- and allografting. Although there are different promising synthetic materials for filling bone defects, the functionalization of these materials with cells is still challenging due to the lack of ideal cell sources. Here, we used stromal vascular fraction (SVF) heterogeneous cells that could be obtained from autologous adipose tissue to functionalize hyaluronic acid/gelatin-biphasic calcium phosphate (HyA-Gel/BCP) scaffolds for bone regeneration. The SVF cells were isolated, and the cellular composition and osteogenic differentiation potential were analyzed. Then, they were cultured on HyA-Gel/BCP scaffolds for in vitro characterization. An In vivo evaluation of the autologous SVF-loaded HyA-Gel/BCP scaffolds was performed using a rat skull critical-size defect model. The results showed that the SVF was successfully isolated and contained different types of cells, including mesenchymal stem like-cells with osteogenic differentiation ability. Also, the SVF cells could be cultured and expanded on the HyA-Gel/BCP scaffolds without affecting their viability. In vivo implantation of autologous SVF-loaded HyA-Gel/BCP scaffolds showed excellent bone regeneration compared to unloaded HyA-Gel/BCP scaffolds. Thus, autologous SVF-loaded HyA-Gel/BCP scaffolds could be a promising transplantable bone grafting material for bone tissue engineering.

Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency-modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic-shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one-third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3-turn crossover design rhombic-shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force-controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties.

Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men.

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.