Monodispersed β‐Glycerophosphate‐Decorated Bioactive Glass Nanoparticles Reinforce Osteogenic Differentiation of Adipose Stem Cells and Bone Regeneration In Vivo

Design and development of highly bioactive nanoscale biomaterials with enhanced osteogenic differentiation on adipose stem cells is rather important for bone regeneration and attracting much attention. Herein, monodispersed glycerophosphate‐decorated bioactive glass nanoparticles (BGN@GP) are designed and their effect is investigated on the osteogenic differentiation of adipose mesenchymal stem cells (ADMSCs) and in vivo bone regeneration. The surface‐modified BGN@GP can be efficiently taken by ADMSCs and shows negligible cytotoxicity. The in vitro results reveal that BGN@GP significantly enhances the alkaline phosphatase activity and calcium biominerialization of ADMSCs either under normal or osteoinductive medium as compared to BGNs. Further studies find that the osteogenic genes and proteins including Runx2 and Bsp in ADMSCs are significantly improved by BGN@GP even under normal culture medium. The in vivo animal experiment confirms that BGN@GP significantly promotes the new bone formation in a rat skull defect model. This study suggests that bioactive small molecule decorating is an efficient strategy to improve the osteogenesis capacity of inorganic ceramics nanomaterials.This paper reports that beta‐glycerophosphate‐functionalized bioactive glass nanoparticles (BGN@GP) could efficiently enhance the uptake of adipose‐derived stem cells (ADSCs) and improve the osteogenic differentiation of ADSCs and reinforce the in vivo bone regeneration, suggesting that BGN@GP is a promising biomaterial for bone tissue repair and regeneration.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154977/1/ppsc201900462.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154977/2/ppsc201900462-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154977/3/ppsc201900462_am.pd

Monodispersed Bioactive Glass Nanoclusters with Ultralarge Pores and Intrinsic Exceptionally High miRNA Loading for Efficiently Enhancing Bone Regeneration

Bioactive glass nanoparticles (BGNs) have attracted much attention in drug delivery and bone tissue regeneration, due to the advantages including biodegradation, high bone‐bonding bioactivity, and facile large‐scale fabrication. However, the wide biomedical applications of BGNs such as efficient gene delivery are limited due to their poor pore structure and easy aggregation. Herein, for the first time, this study reports novel monodispersed bioactive glass nanoclusters (BGNCs) with ultralarge mesopores (10–30 nm) and excellent miRNA delivery for accelerating critical‐sized bone regeneration. BGNCs with different size (100–500 nm) are fabricated by using a branched polyethylenimine as the structure director and catalyst. BGNCs show an excellent apatite‐forming ability and high biocompatibility. Importantly, BGNCs demonstrate an almost 19 times higher miRNA loading than those of conventional BGNs. Additionally, BGNCs–miRNA nanocomplexes exhibit a significantly high antienzymolysis, enhance cellular uptake and miRNA transfection efficiency, overpassing BGNs and commercial Lipofectamine 3000. BGNCs‐mediated miRNA delivery significantly improves the osteogenic differentiation of bone marrow stromal stem cells in vitro and efficiently enhances bone formation in vivo. BGNCs can be a highly efficient nonviral vector for various gene therapy applications. The study may provide a novel strategy to develop highly gene‐activated bioactive nanomaterials for simultaneous tissue regeneration and disease therapy.Monodispersed bioactive glass nanoclusters (BGNCs) with ultra‐large mesopores (10–30 nm) are developed for miRNA delivery to enhance bone regeneration. BGNCs demonstrated an ultrahigh miRNA loading and transfection efficiency, overpassing commercial lipofectamine. BGNCs‐mediated miRNA delivery significantly improved osteogenic differentiation of bone marrow stromal stem cells in vitro and enhanced bone formation in vivo.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139128/1/adhm201700630-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139128/2/adhm201700630.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139128/3/adhm201700630_am.pd

Injectable Self‐Healing Antibacterial Bioactive Polypeptide‐Based Hybrid Nanosystems for Efficiently Treating Multidrug Resistant Infection, Skin‐Tumor Therapy, and Enhancing Wound Healing

The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.This paper reports an intrinsically multifunctional bioactive hybrid hydrogel for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The hybrid hydrogels display excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo, and also efficiently inhibits tumor growth and enhances wound healing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149555/1/adfm201806883.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149555/2/adfm201806883-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149555/3/adfm201806883_am.pd

Monodisperse Branched Molybdenum‐Based Bioactive Nanoparticles Significantly Promote Osteogenic Differentiation of Adipose‐Derived Stem Cells

Adipose‐derived stem cells (ADSCs) are considered to be ideal stem cell sources for bone‐tissue regeneration owing to their ease of collection and high activity. However, the regulation of osteogenic differentiation of ADSCs using biomaterials without adding growth factors is still not satisfactory. For the first time, molybdenum‐doped bioactive glass nanoparticles with a radial porous morphology (Mo‐rBGNs) are reported and their role in the osteogenic differentiation of ADSCs is investigated. The results show that Mo‐rBGNs exhibit radially porous and spherical morphology, relatively homogeneous particle size (200–400 nm), and excellent apatite‐forming bioactivity. They do not affect the proliferation of ADSCs, but significantly regulate their osteogenic differentiation and biomineralization. 5% Mo‐rBGNs significantly enhance the alkaline phosphatase activity and biomineralization ability and promote the osteogenic gene expressions of collagen I secretion and bone sialo protein in ADSCs. A reasonable and promising strategy for designing nanoscale bioactive materials with the excellent osteogenic ability for stem cell–based bone tissue regeneration is provided.Molybdenum‐doped bioactive glass nanoparticles with a radial porous morphology (Mo‐rBGNs) are reported. Mo‐rBGNs exhibit excellent apatite‐forming bioactivity and significantly regulate the osteogenic differentiation and biomineralization of adipose‐derived stem cells (ADSCs). 5% Mo‐rBGNs significantly enhance the alkaline phosphatase activity and osteogenic gene expressions of collagen I secretion and bone sialo protein in ADSCs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150603/1/ppsc201900105-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150603/2/ppsc201900105.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150603/3/ppsc201900105_am.pd

Altered expression of inflammation-associated molecules in striatum: an implication for sensitivity to heavy ion radiations

Background and objectiveHeavy ion radiation is one of the major hazards astronauts face during space expeditions, adversely affecting the central nervous system. Radiation causes severe damage to sensitive brain regions, especially the striatum, resulting in cognitive impairment and other physiological issues in astronauts. However, the intensity of brain damage and associated underlying molecular pathological mechanisms mediated by heavy ion radiation are still unknown. The present study is aimed to identify the damaging effect of heavy ion radiation on the striatum and associated underlying pathological mechanisms.Materials and methodsTwo parallel cohorts of rats were exposed to radiation in multiple doses and times. Cohort I was exposed to 15 Gy of 12C6+ ions radiation, whereas cohort II was exposed to 3.4 Gy and 8 Gy with 56Fe26+ ions irradiation. Physiological and behavioural tests were performed, followed by 18F-FDG-PET scans, transcriptomics analysis of the striatum, and in-vitro studies to verify the interconnection between immune cells and neurons.ResultsBoth cohorts revealed more persistent striatum dysfunction than other brain regions under heavy ion radiation at multiple doses and time, exposed by physiological, behavioural, and 18F-FDG-PET scans. Transcriptomic analysis revealed that striatum dysfunction is linked with an abnormal immune system. In vitro studies demonstrated that radiation mediated diversified effects on different immune cells and sustained monocyte viability but inhibited its differentiation and migration, leading to chronic neuroinflammation in the striatum and might affect other associated brain regions.ConclusionOur findings suggest that striatum dysfunction under heavy ion radiation activates abnormal immune systems, leading to chronic neuroinflammation and neuronal injury

Advances in the application of co-culture strategies in organoids

As a good in vitro research model, organoids are more and more widely used in the biomedical field. By developing self-assembled 3D structures using various tissue culture techniques, organoids can rebuild the high complexity of cells in the inherent structure of the organ, and are therefore unanimously used to study mechanisms regulating body development and disease, high-throughput drug screening, and personalized treatment and so on. To better recapitulate cell-to-cell interactions within the microenvironment, co-culture strategies have been extended to more cell types, and their rapid development offers broader prospects for organoids and paves the way for the treatment of human diseases and regenerative medicine. This review discussed the role of co-culture strategies in organoid generation, and focused on the application of various cellular components and microorganisms in organoid construction, thereby providing reference and help for scholars to construct and develop organoids with a higher degree of in vivo simulation

Simulation and analysis of microring electric field sensor based on a lithium niobate-on-insulator

With the increasing sensitivity and accuracy of contemporary high-performance electronic information systems to electromagnetic energy, they are also very vulnerable to be damaged by high-energy electromagnetic fields. In this work, an all-dielectric electromagnetic field sensor is proposed based on a microring resonator structure. The sensor is designed to work at 35 GHz RF field using a lithium niobate-on-insulator (LNOI) material system. The 2.5-D variational finite difference time domain (varFDTD) and finite difference eigenmode (FDE) methods are utilized to analyze the single-mode condition, bending loss, as well as the transmission loss to achieve optimized waveguide dimensions. In order to obtain higher sensitivity, the quality factor (Q-factor) of the microring resonator is optimized to be 106 with the total ring circumference of 3766.59 μm. The lithium niobate layer is adopted in z-cut direction to utilize TM mode in the proposed all-dielectric electric field sensor, and with the help of the periodically poled lithium niobate (PPLN) technology, the electro-optic (EO) tunability of the device is enhanced to 48 pm·μm/V