Long non-coding RNA Snhg15 promotes preosteoblast proliferation by interacting with and stabilizing nucleolin.

The proliferation and mineralization of preosteoblasts is crucial for bone formation and has attracted extensive attentions for decades. However, the roles of numerous long non-coding RNAs (lncRNAs) in preosteoblasts have not been fully determined. This study aimed to investigate the function of lncRNA Snhg15 in preosteoblasts as well as the potential underlying mechanism. LncRNA Snhg15 was dynamically expressed during preosteoblast proliferation and mineralization, and its transcripts were localized mainly in the cytoplasm. LncRNA Snhg15 knockdown significantly inhibited the proliferation and mineralization of preosteoblasts in both a cellular model and a murine ectopic bone formation model. RNA-seq showed that lncRNA Snhg15 knockdown downregulated multiple proliferation-related genes, and cell cycle deregulation was verified by flow cytometry. Mechanistically, we found that lncRNA Snhg15 could bind to nucleolin (NCL), thereby block NCL ubiquitination and decrease its degradation. Furthermore, the overexpression of NCL in lncRNA Snhg15-knockdown preosteoblasts ameliorated GO/G1 phase cell cycle arrest. Moreover, experiments in an in situ bone formation model confirmed the negative effects of lncRNA Snhg15 deficiency on bone formation. In conclusion, this study revealed an important regulatory role of lncRNA Snhg15/NCL complex in preosteoblast proliferation and may provide insights into the molecular mechanisms underlying bone formation.

Biomimetic chitosan-derived bifunctional lubricant with superior antibacterial and hydration lubrication performances.

The lubrication deficiency in joints is a major cause of osteoarthritis. One of the most commonly used treatment means is to inject artificial lubricants, but there is a potential risk of infection during the injection process. Therefore, developing artificial lubricants with dual functions of friction-reduction and antibacterial is urgent. In this work, a novel polysaccharide-derived lubricant with simultaneous anti-bacteria and water-lubrication properties, called CS-MPC-N, is developed by grafting 2­methacryloyloxylethyl phosphorylcholine (MPC) and nisin peptide onto backbone of chitosan (CS). Compared to the control CS, CS-MPC-N exhibits good lubrication and friction-reduction properties because of its excellent water solubility. Especially, CS-MPC-N shows low friction coefficient (0.03 âˆ¼ 0.05) at the sliding interfaces of artificial joints materials or even natural articular cartilages. Moreover, CS-MPC-N can effectively inhibit the proliferation of Staphylococcus aureu, exhibiting excellent antibacterial effect. This kind of novel polysaccharide-derived lubricant is expected to be used in treating infectious arthritis.

An excellent antibacterial and high self-adhesive hydrogel can promote wound fully healing driven by its shrinkage under NIR.

The lacks of antibacterial properties, low adhesion and delayed wound healing of the hydrogel wound dressings limit their applications in wound treatment. To resolve these, a novel hydrogel composed of polydopamine (PDA), Ag and graphene oxide (GO) is fabricated for wound dressing via the chemical crosslinking of N-isopropylacrylamide (NIPAM) and N,N'-methylene bisacrylamide (BIS). The prepared hydrogel containing PDA@Ag5GO1 (Ag5GO1 denotes the mass ratio between Ag and GO is 5:1) exhibits effective antibacterial properties and high inhibition rate against E. coli and S. aureus. It shows high adhesion ability to various substrate materials, implying a simpler method to the wound obtained by self-fixing rather than suturing. More important, it can produce strong contractility under the irradiation of near-infrared light (NIR), exerting a centripetal force that helps accelerate wound healing. Thus, the hydrogel containing a high concentration PDA@Ag5GO1 irradiated by NIR can completely repair the wound defect (1.0 × 1.0 cm2) within 15 days, the wound healing rate can reach 100%, which was far higher than other groups. Taken together, the new hydrogel with excellent antibacterial, high adhesion and strong contractility will subvert the traditional treatment methods on wound defect, extending its new application range in wound dressing.

Near-Infrared Light-Triggered Unfolding Microneedle Patch for Minimally Invasive Treatment of Myocardial Ischemia.

It is hard to achieve safe, effective, and minimally invasive therapies on myocardial infarction (MI) via conventional treatments. To address this challenge, a vascular endothelial growth factor (VEGF)-loaded and near-infrared (NIR)-triggered self-unfolding graphene oxide (GO)-poly(vinyl alcohol) (PVA) microneedle (MN) patch was designed and fabricated to treat MI through a minimally invasive surgery (MIS). The folded MN patch can be easily placed into the chest cavity through a small cut (4 mm) and quickly recover to its original shape with 10 s of irradiation of NIR light (1.5 W/cm2, beam diameter = 0.5 cm), thanks to its excellent shape memory effect and fast shape recovery ability. Meanwhile, the unfolded MN patch can be readily punctured into the heart and wrap the heart tightly, thanks to its sufficient mechanical strength and adjustable morphological structure, thus ensuring a high fixation strength to withstand the high-frequency pulsation of the heart. In addition, the prepared MN patch has low cytotoxicity and controllable and sustainable release of VEGF. More importantly, the MN patch can effectively promote neovascularization, reduce myocardial fibrosis, and restore cardiac function, which indicates its promising application prospects in MIS.

Converting Complex Sewage Containing Oil, Silt, and Bacteria into Clean Water by a 3D Printed Multiscale and Multifunctional Filter.

The exacerbating water pollution and water resource shortage pose a great danger to human health and make it imperative to recycle and treat the sewage. In this study, a direct-writing three-dimensional (3D) printing technology was adopted to prepare a 3D sodium alginate (SA)/graphene oxide (GO)/Ag nanoparticle (AgNP) aerogel (SGA), aiming to turn the complex sewage containing oil, silt, and bacteria into clean water depending only on gravity separation. The physicochemical properties and surface structure of the synthesized SGA were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The swelling rate, mechanical properties, antibacterial properties, oil and water separation effect, and durable stability of the filter membrane were also investigated to verify the versatility of the SGA filter. The results showed that GO helped improve the mechanical properties of the printed filter to withstand water impact during the filtration process. The printed filter had a well-designed and multiscale gradient pore structure, which can effectively intercept particles with different sizes to separate the silt from water, and the turbidity of the filtered water can be reduced from 60 to 1 nephelometric turbidity unit (NTU). The presence of SA endowed the printed filter with hydrophilic and oleophobic behaviors, which can effectively separate various kinds of oils from water. The uniform distribution of AgNPs in the filter produced via a facile and green reduction of SA facilitated the efficient bactericidal ability of the printed filter during the filtration process; meanwhile, the lower release concentration of Ag ions ensured drinking safety. What is more, the filter can be easily produced on a large scale and used for different sewage treatment situations with a durable stability of over 30 days. Taken together, the printed SGA filter has a broad application prospect in complex sewage treatment, providing a special solution for sewage treatment in poverty areas.

Au@polydopamine nanoparticles/tocilizumab composite as efficient scavengers of oxygen free radicals for improving the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common chronic autoimmune disorder associated with high-cost, side effects, and low therapeutic effects. To improve the treatment of RA, we originally developed a novel anti-RA Au@polydopamine nanoparticles (PDANPs)/TCZ composite using PDANPs as the binding sites of gold nanoparticles (AuNPs) and the drug carries of tocilizumab (TCZ) through a facile and environmentally-friend method, aiming to effectively scavenge oxygen free radicals (OFR) and inhibit the formation of related inflammatory factors. Characterizations showed that AuNPs with the size of 11.4 ± 2.9 nm randomly distributed onto the surface of PDANPs (145.8 ± 31.9 nm), meanwhile TCZ was chemically cross-linked to PDANPs through Schiff base linkage. The synthesized composite had good biocompatibility that can promote the proliferation and growth of chondrocytes and fibroblasts. More importantly, Au@PDANPs/TCZ composite showed more excellent abilities to scavenge OFR and inhibit the related inflammatory factors in vitro and in vivo than that of AuNPs and PDANPs owing to the synergistic scavenging effect, ensuring its best therapeutic effect in RA therapy. This new composite will have application potential in the treatment of RA related disease.

Novel pre-vascularized tissue-engineered dermis based on stem cell sheet technique used for dermis-defect healing.

Insufficient donor dermis and the shortage of three-dimensional vascular networks are the main limitations in the tissue-engineered dermis (TED). To solve these problems, we initially constructed pre-vascularized bone marrow mesenchymal stem cell sheet (PBMCS) and pre-vascularized fibroblasts cell sheet (PFCS) by cell sheet technology, and then superimposed or folded them together to construct a pre-vascularized TED (PTED), aiming to mimic the real dermis structure. The constructed PTED was implanted in nude mice dorsal dermis-defect wound and the wound-healing effect was quantified at Days 1, 7 and 14 via the methods of histochemistry and immunohistochemistry. The results showed that PTED could rapidly promote the wound closure, especially at Day 14, and the wound-healing rate of three-layer PTED could reach 97.2% (P < 0.01), which was faster than the blank control group (89.1%), PBMCS (92.4%), PFCS (93.8%) and six-layer PTED (92.3%). In addition, the vessel density in the PTED group was higher than the other groups on the 14th day. Taken together, it is proved that the PTED, especially three-layer PTED, is more conducive to the full-thickness dermis-defect repair and the construction of the three-dimensional vascular networks, indicating its potential application in dermis-defect repair.

A prevascularized nerve conduit based on a stem cell sheet effectively promotes the repair of transected spinal cord injury.

Spinal cord injury (SCI) can result in severe loss of motor and sensory function caused by ischemia and hypoxia, which are the key limiting factors of SCI rehabilitation. Vascularization is considered an effective way to resolve the issues of ischemia and hypoxia. In this regard, we first fabricated prevascularized nerve conduits (PNC) based on the prevascularized stem cell sheet and evaluated their repair effects by implanting them into transected SCI rats. A better healing effect was presented in the PNC group than in the control group and the nonprevascularized nerve conduit (NPNC) group as shown in H&E staining and the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale assessment. In addition, the expression of ß-III tubulin (Tuj-1) in the PNC group was higher than that in the control group and the NPNC group because of the introduction of MSCs. Conversely, the expression of the glial fibrillary acidic protein (GFAP) in both experimental groups was lower than that in the control group because of the inhibitory effect of MSCs on glial scar formation. Taken together, the introduction of prevascularization into the neuron conduit was an effective solution for improving the condition of ischemia and hypoxia, inhibiting glial scar formation, and promoting the healing of SCI, which implied that the PNC may be a potential alternative material to biomaterials for SCI rehabilitation. STATEMENT OF SIGNIFICANCE: 1. Prevascularized stem cell sheet was first used to repair spinal cord injury (SCI). 2. Prevascularized stem cell sheet use can effectively resolve the challenges faced during SCI, including ischemia and hypoxia and the limited regenerative ability of the remained neurons. 3. Prevascularized stem cell sheet was found to accelerate the healing of SCI as compared to those in the control group and the pure stem cell sheet group. 4. The introduction of stem cells can effectively inhibit the formation of a glial scar.

Facile and large-scale synthesis of graphene quantum dots for selective targeting and imaging of cell nucleus and mitochondria.

Graphene quantum dots (GQDs) have good biocompatibility, high luminescence, and low photobleaching properties, which make them promising alternatives to fluorescent dyes for cell imaging. However, most of the reported GQDs lack targeted selectivity that limits their applications in biomedicine. To overcome the drawback, novel GQDs modified with polyethyleneimine (PEI) or (3-carboxyl) phenyl bromide phosphine (TPP) were originally synthesized via a facile, low-cost, environmentally friendly, and large-scale preparation method. The GQDs-PEI was synthesized by a simple hydrothermal process, and then TPP was conjugated to the GQDs-PEI via the amide linkage. The physicochemical, optical, biocompatible, and targeted imaging properties were evaluated systematically. The results indicated that the average sizes of the as-produced GQDs-PEI and GQDs-TPP were 3.75 and 3.25 nm, respectively. More significantly, the two composites had excellent optical property, low cytotoxicity and selective targeting and imaging properties for cell nucleus or mitochondria, suggesting their promising applications as the cell nucleus imaging or mitochondria imaging in vivo and in vitro for diagnosis and therapy of some related diseases.

Novel chitosan hydrogels reinforced by silver nanoparticles with ultrahigh mechanical and high antibacterial properties for accelerating wound healing.

Poor mechanical properties of chitosan hydrogels limit their applications as the wound dressing. To overcome this drawback, we abandoned the traditional glacial acetic acid method but adopted a LiOH/urea solvent system to synthesize chitosan hydrogel. Then reductive Ag nanoparticles were integrated into the chitosan hydrogel networks, aiming at reinforcing the mechanical properties and improving the antibacterial properties of chitosan hydrogel. The synthesized hydrogels were subsequently characterized using the FTIR, XRD, SEM, and TEM. In addition, swelling characteristics, mechanical properties, antibacterial abilities as well as wound healing efficacy on Sprague-Dawley rats were evaluated. The results showed that the novel hydrogel exhibited porous three-dimensional network and ultrahigh mechanical properties due to the inter-molecular and intra-molecular interactions. The compressive strength was 15.95 ±â€¯1.95 MPa, >100 times stronger than that of the control group. Meanwhile, the hydrogels still remained structural integrity even if the strain exceeded 90%. Furthermore, compared with the controls, the hydrogels exhibited more excellent antibacterial performance and significantly (p < 0.05) increased the rate of the re-epithelialization and collagen deposition, effectively accelerating the wound healing. Therefore, the synthesized hydrogel with ultrahigh mechanical properties will be found potential applications in the fields of biomedicine.

Facile and large-scale synthesis of curcumin/PVA hydrogel: effectively kill bacteria and accelerate cutaneous wound healing in the rat.

The complicated synthesis procedure and limited preparation size of hydrogel inhibit its clinical application. Therefore, a facile preparation method for large-size hydrogel is required. In this study, a series of curcumin (Cur)/polyvinyl alcohol (PVA) hydrogel in a large size with different Cur concentrations is prepared by a facile physical-chemical crosslinking. The physicochemical properties, antibacterial performance and accelerating wound healing ability are evaluated with the aim of attaining a novel and effective wound dressing. The results show that the as-prepared hydrogel with the optimal Cur to PVA volume ratio of 1:5 (20% Cur/PVA) exhibits the best antibacterial abilities to E. coli (85.6%) and S. aureus (97%) than other hydrogels. When the volume ratio of Cur to PVA is 1:10 (10% Cur/PVA), the hydrogel can significantly accelerate the wound healing in rats, and successfully reconstruct intact and thickened epidermis during 14 day of healing of impaired wounds after histological examination. In one word, the present approach can shed new light on designing new type of hydrogels with promising applications in wound dressing.