Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

Small Extracellular Vesicles Released from Bioglass/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p

Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. MSCs-derived small extracellular vesicles (sEVs) show desirable therapeutic prospects in tissue regeneration due to satisfied advantages including high stability, facilitated acquisition and abundant source. However, the effect of Human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the potential mechanism of sEVs on the effects of osteogenesis and angiogenesis by luciferase reporter gene assay and western blot. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs(BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finds illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

CHOOSING THE OPTIMUM TECHNOLOGICAL ALTERNATIVE FOR 3D PRINTING

The period between the design of a product and the moment from which the product is no longer profitable on the market represents its life cycle. Decreasing the profitability of the product on the market means that the company must find solutions to launch a new product. The new products can be assimilated in the manufacture by own conception at the level of the enterprise, on the basis of the purchased manufacturing licenses and on the basis of the reference models of a similar product existing on the market. The paper presents the methodology for choosing the optimal technological variant for a part manufactured by 3D printing using two technological variants, through the criterion of unit technological cost and the criterion of total technological cost. Depending on the relationship between the size of the manufacturing batch and the calculated critical size of the manufacturing batch, respectively between the unit technological cost and the total technological cost for the two technological variants, the optimal technological variant of manufacturing can be established.

Nanocomposites of Chitosan/Graphene Oxide/Titanium Dioxide Nanoparticles/Blackberry Waste Extract as Potential Bone Substitutes

New technologies based on nanocomposites of biopolymers and nanoparticles inspired by the nature of bone structure have accelerated their application in regenerative medicine, thanks to the introduction of reinforcing properties. Our research incorporated chitosan (CS) covalently crosslinked with glutaraldehyde (GLA) beads with graphene oxide (GO) nanosheets, titanium dioxide nanoparticles (TiO2), and blackberry processing waste extract (BBE) and evaluated them as partial bone substitutes. Skullbone defects in biomodels filled with the scaffolds showed evidence through light microscopy, scanning electron microscopy, histological studies, soft tissue development with hair recovery, and absence of necrotic areas or aggressive infectious response of the immune system after 90 days of implantation. More interestingly, newly formed bone was evidenced by elemental analysis and Masson trichromacy analysis, which demonstrated a possible osteoinductive effect from the beads using the critical size defect experimental design in the biomodels. The results of this research are auspicious for the development of bone substitutes and evidence that the technologies for tissue regeneration, including chitosan nanocomposites, are beneficial for the adhesion and proliferation of bone cells.

Controlled Growth of Silicon Particles via Plasma Pulsing and their Application as Battery Material

The use of silicon nanoparticles for lithium-ion batteries requires a precise control over both their average size and their size distribution. Particles larger than the generally accepted critical size of 150 nm fail during lithiation because of excessive swelling, while very small particles (<10 nm) inevitably lead to a poor first cycle coulombic efficiency because of their excessive specific surface area. Both mechanisms induce irreversible capacity losses and are detrimental to the anode functionality. In this manuscript we describe a novel approach for enhanced growth of nanoparticles to ~20 nm using low-temperature flow-through plasma reactors via pulsing. Pulsing of the RF power leads to a significant increase in the average particle size, all while maintaining the particles well below the critical size for stable operation in a lithium-ion battery anode. A zero-dimensional aerosol plasma model is used to investigate the dynamics of particle agglomeration and growth in the pulsed plasma reactor. The accelerated growth correlates with the shape of the particle size distribution in the afterglow, which is in turn controlled by parameters such as metastable density, gas and electron temperature. The accelerated agglomeration in each afterglow phase is followed by rapid sintering of the agglomerates into single-crystal particles in the following plasma-on phase. This study highlights the potential of non-thermal plasma reactors for the synthesis of functional nanomaterials, while also underscoring the need for better characterization of their fundamental parameters in transient regimes.