Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Hydrogel-Coated Microelectrode Resists Protein Passivation of In Vivo Amperometric Sensors.

Passivation of electrodes caused by nonspecific adsorption of protein can dramatically reduce sensing sensitivity and accuracy, which is a great challenge for in vivo neurochemical monitoring. However, most antipassivation strategies are not suitable to carbon fiber microelectrodes (CFMEs) for in vivo measurement, and these methods also do not work on electrochemical biosensors that fix biometric elements. In this study, we demonstrate that chitosan hydrogel-coated microelectrodes can avoid the current passivation caused by protein adsorption on the surface of carbon fiber because the chitosan hydrogel prepared by local pH gradient caused by hydrogen evolution reaction has three-dimensional networks containing large amounts of water. The highly hydrophilic three-dimensional structure of hydrogel not only forms a biocompatible interface to confine enzymes but also keeps the fast mass transfer of analytes, such as dopamine, ascorbic acid, and glucose. The consistency of the precalibration and postcalibration of the prepared sensor enables in vivo amperometric detection of both electroactive species based on their redox property and electroinactive species based on the enzyme. This study provides a simple and versatile strategy to constitute an amperometric sensor interface to resist passivation of protein adsorption in a complex biological environment such as the brain.

Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva.

The construction of low-fouling biosensors for assaying biomarkers in complex biological samples remains a challenge, and the key limitation is the lack of effective anti-fouling materials. Inspired by the biomimetic process of protein phosphorylation, we herein designed a new phosphorylated peptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicity and anti-fouling capability of the peptide when compared with natural and normal peptides. Molecular simulation (MS) illustrated that, compared with the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bonds and stronger hydrogen bonds with water molecules. As a result, the PO4H2-oligopeptide was proved by MS to be able to attract the greatest number of water molecules, so as to form a compact layer of H2O to resist further adsorption of nonspecific biomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption of neutral peptide nucleic acids (PNAs) as the sensing probes, ensured the fabrication of anti-fouling electrochemical biosensors capable of detecting nucleic acids in complex saliva. The constructed anti-fouling biosensor was able to detect the nucleic acid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva, with a wide linear response range (0.01 pM-0.01 µM) and a low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylation of oligopeptides offers an effective strategy to designing ultra-hydrophilic peptides suitable for the construction of promising anti-biofouling biosensors and bioelectronics.

Microplastics Weaken the Adaptability of Cyanobacterium Synechococcus sp. to Ocean Warming.

Ocean warming (OW) caused by anthropogenic activities threatens ocean ecosystems. Moreover, microplastic (MP) pollution in the global ocean is also increasing. However, the combined effects of OW and MPs on marine phytoplankton are unclear. Synechococcus sp., the most ubiquitous autotrophic cyanobacterium, was used to evaluate the response to OW + MPs under two warming scenarios (28 and 32 °C compared to 24 °C). The enhancement of the cell growth rate and carbon fixation under OW were weakened by MP exposure. Specifically, OW + MPs reduced carbon fixation by 10.9 and 15.4% at 28 and 32 °C, respectively. In addition, reduction in photosynthesis pigment contents of Synechococcus sp. under OW was intensified under OW + MPs, supporting the lower growth rate and carbon fixation under OW + MPs. Transcriptome plasticity (the evolutionary and adaptive potential of gene expression in response to changing environments) enabled Synechococcus sp. to develop a warming-adaptive transcriptional profile (downregulation of photosynthesis and CO2 fixation) under OW. Nevertheless, the downregulation of photosynthesis and CO2 fixation were alleviated under OW + MPs to increase responsiveness to the adverse effect. Due to the high abundances of Synechococcus sp. and its contributions to primary production, these findings are important for understanding the effects of MPs on carbon fixation and ocean carbon fluxes under global warming.

Support-Free PEDOT:PSS Fibers as Multifunctional Microelectrodes for In Vivo Neural Recording and Modulation.

In vivo microelectrodes are essential for neuroscience studies. However, development of microelectrodes with both flexibility and multifunctionality for recording chemical and electrical signals in the same extracellular microspace and modulating neural activity remains challenging. Here, we find that pure PEDOT:PSS fibers (i.e., support-free) exhibit high conductivity, fast heterogeneous electron transfer, and suitable charge storage and injection capabilities, and can thus directly act as microelectrodes not only for chemical and electrophysiological recording in the same extracellular microspace, but also for electromodulation of neural microcircuit activity. Moreover, the microelectrodes mechanically match with neural tissues, exhibiting less foreign body responses. Given the multifunctionality, flexibility, and biocompatibility, the support-free PEDOT:PSS-based microelectrodes offer a new avenue to microelectrode technology for neuroscience research, diagnostics and therapeutics.

Effects of Drynaria Total Flavonoid on the Microstructure of the Mandible in Ovariectomized Rats.

BACKGROUND The aim of this study is to investigate the effects of Drynaria total flavonoids (DTF) on mandible microarchitecture, serum estrogen (E2), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in an ovariectomy-induced osteoporosis rat model. MATERIAL AND METHODS Thirty female Sprague-Dawley rats were divided into 5 groups (n=6 per group): sham surgery, ovariectomy (OVX), and low-dose, middle-dose, and high-dose DTF. Mandibular osteoporosis was induced by ovariectomy; an equal amount of ovary-sized fat tissue was removed from the sham group. The DTF-treated groups were given DTF gavage at different doses for 12 weeks; the sham and OVX groups were given saline. After the treatment phase, the effects of DTF on the microarchitecture of the mandible were evaluated by measuring bone density, maximum load, morphometric parameters, and histopathological alterations. Serum E2, OPG, and RANKL levels were measured. RESULTS The OVX group showed obvious osteoporosis in the mandible and decreased serum E2 levels and OPG/RANKL ratio. The low-dose group did not show significant improvement in mandibular microstructure. The middle-dose group showed significantly ameliorated osteoporosis. The high-dose group had further improvement in bone microstructures and increase of OPG/RANKL over the middle-dose group. Furthermore, ovariectomy significantly decreased serum E2, but DTF treatment failed to restore serum E2 levels. CONCLUSIONS Ovariectomy can cause significant bone loss in the rat mandible and a decrease in serum E2 and OPG/RANKL. DTF significantly improved the mandibular microstructure and restored OPG/RANKL balance, but it did not restore the decreased serum E2 concentration following ovariectomy.

Charge Reversible and Mitochondria/Nucleus Dual Target Lipid Hybrid Nanoparticles To Enhance Antitumor Activity of Doxorubicin.

The experiment aims to increase antitumor activity while decreasing the systemic toxicity of doxorubicin (DOX). Charge reversible and mitochondria/nucleus dual target lipid hybrid nanoparticles (LNPs) was prepared. The in vitro experimental results indicated that LNPs released more amount of DOX in acidic environment and delivered more amount of DOX to the mitochondria and nucleus of tumor cells than did free DOX, which resulted in the reduction of mitochondrial membrane potential and the enhancement of cytotoxicity of LNPs on tumor cells. Furthermore, the in vivo experimental results indicated that LNPs delivered more DOX to tumor tissue and significantly prolonged the retention time of DOX in tumor tissue as compared with free DOX, which consequently resulted in the high antitumor activity and low systemic toxicity of LNPs on tumor-bearing nude mice. The above results indicated that charge reversible mitochondria/nucleus dual targeted lipid hybrid nanoparticles greatly enhanced therapeutic efficacy of DOX for treating lung cancer.

[A de novo GJA1 mutation identified by whole-exome sequencing in a patient with oculodentodigital dysplasia].

OBJECTIVE: To explore the genetic basis for a patient with oculodentodigital dysplasia. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole-exome sequencing was carried out for the trio family. Suspected mutation was verified by Sanger sequencing. RESULTS: A de novo c.412G>A mutation of the GJA1 gene was identified in the patient, which was validated by Sanger sequencing. CONCLUSION: The c.412G>A mutation of the GJA1 gene probably underlies the disease in the patient.

Mitochondria and Nucleus Dual Delivery System To Overcome DOX Resistance.

Doxorubicin (DOX) is a broad-spectrum chemotherapy drug to treat tumors. However, severe side effects and development of DOX resistance hinder its clinical application. In order to overcome DOX resistance, DOX/TPP-DOX@Pasp-hyd-PEG-FA micelles were prepared by using newly synthesized comb-like amphiphilic material Pasp-hyd-PEG-FA. Drug released in vitro from micelles showed a pH-dependent manner. DOX/TPP-DOX@Pasp-hyd-PEG-FA induced more apoptosis in KB cell and MCF-7/ADR cell than DOX@Pasp-hyd-PEG-FA. Confocal laser scanning microscopy experiment indicated that DOX/TPP-DOX@Pasp-hyd-PEG-FA delivered TPP-DOX and DOX to the nucleus and mitochondria of the tumor cell simultaneously. Thus, DOX/TPP-DOX@Pasp-hyd-PEG-FA could significantly damage the mitochondrial membrane potential. DOX/TPP-DOX@Pasp-hyd-PEG-FA markedly shrinked the tumor volume in tumor-bearing nude mice grafted with MCF-7/ADR cell as compared with the same dose of free DOX. DOX was mainly accumulated in tumor tissue after DOX/TPP-DOX@Pasp-hyd-PEG-FA was injected to tumor-bearing nude mice by tail vein. After free DOX was injected to tumor-bearing nude mice by tail vein, DOX widely distributed through the whole body. Therefore, mitochondria and nucleus dual delivery system has potential in overcoming DOX resistance.

Lanthanide Coordination Polymer Nanoparticles as an Excellent Artificial Peroxidase for Hydrogen Peroxide Detection.

Lanthanide coordination polymer nanoparticles (Ln-CPNs) have been recently demonstrated as excellent platforms for biomolecule detection. In this work, we synthesized novel cerium coordination polymer nanoparticles ATP-Ce-Tris CPNs in a simple and quick way using ATP molecules as the biocompatible ligands to Ce(3+) ions in tris(hydroxymethyl)aminomethane hydrochloric (Tris-HCl) solution. In view of the excellent free radical scavenging property of cerium compounds, which is ascribed to the mixed valence state (Ce(3+), Ce(4+)) and the reversible switch from Ce(3+) to Ce(4+), the synthesized ATP-Ce-Tris CPNs was used as artificial peroxidase to selectively and sensitively detect H2O2. The sensing mechanism depends on the oxidation of the fluorescent ATP-Ce(III)-Tris CPNs to nonfluorescent ATP-Ce(IV)-Tris CPNs by H2O2. Compared with those inorganic cerium oxide sensors, this kind of fluoresence ATP-Ce-Tris CPNs sensor needs no additional organic redox dye, such as ABTS (2,20-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), TMB (3,3,5,5-tetramethylbenzidine), or fluorescein as signal molecules. Moreover, such ATP-Ce-Tris CPNs sensor exhibited a more sensitive response to H2O2 with a detection limit down to 0.6 nM, which is 2 orders of magnitude lower than those of cerium oxide sensors. This sensing platform was further extended to the detection of glucose in combination with the specific catalytic effect of glucose oxidase (GOx) for the oxidation of glucose and formation of H2O2.

pH-Triggered Surface Charge Reversed Nanoparticle with Active Targeting To Enhance the Antitumor Activity of Doxorubicin.

PLGA nanoparticles are widely used in tumor targeting drug delivery systems. However, the naked PLGA nanoparticles (NNPs) not only have low drug loading but also can be rapidly removed from blood circulation by the immune system. The aim of this study was to prepare pH-triggered surface charge reversed lipid hybrid PLGA nanoparticles (LNPs) to enhance drug loading and drug delivery efficiency. CHO-Arg-His-OMe and FA-PEG-DSPE were synthesized to modify PLGA nanoparticles to prepare LNPs. The drug loading and encapsulation rate of LNPs were greatly improved as compared with NNPs. In pH 7.4 medium, doxorubicin (DOX)-loaded LNPs showed negative charge and released DOX slowly. In pH 5.0 medium, DOX-loaded LNPs exhibited positive charge and released DOX quickly. DOX-loaded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR cells than did free DOX. In addition, DOX-loaded LNPs significantly inhibited the proliferation of KB cells and MBA-MD-231/ADR cells. Compared with free DOX, the same dose of the DOX-loaded LNPs delivered more DOX to tumor tissue. Thus, DOX-loaded LNPs significantly inhibited the growth of tumor in tumor-bearing nude mice and obviously reduced the systemic toxicity of DOX. In conclusion, pH-triggered surface charge reversed DOX-loaded LNPs significantly enhanced the antitumor activity of DOX in vitro and in vivo. DOX-loaded LNPs had great potential in tumor targeted chemotherapy.

Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF.

Influences of IL-6R antibody on PMMA bone cement-mediated expression of OPG and RANKL in synovial fibroblasts.

Effect of interleukin-6 receptor (IL-6R) antibody on polymethyl methacrylate (PMMA) bone cement-mediated expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) in synovial fibroblasts was investigated. Synovial tissue obtained from total knee arthroplasty was digested and cultured. Inverted microscope was employed to observe the synovial cells and immunocytochemistry (SABC method) staining was used to identify synovial fibroblasts. This experiment was divided into three groups according to different culture media: PMMA group (75 µg/mL PMMA bone cement particles), IL-6R antibody group (10 ng/mL IL-6R antibody+75 µg/mL PMMA bone cement particles), and control group (no IL-6R antibody or PMMA bone cement particles). Influence of IL-6R antibody and PMMA on proliferation of synovial fibroblasts was measured by cell counting kit-8 (CCK-8). ELISA method was used to measure OPG and RANKL levels in culture solution. Fluorescence quantitative real-time PCR (FQ-PCR) was used to detect the expression of OPG and RANKL mRNA. After three consecutive passages, more than 95% of the primary synovial cells became long spindle fibroblast-like cells. SABC staining results showed that the fibroblast-like cells were negative for anti-CD68 antibody and positive for anti-vimentin antibody, with brown madder stained. CCK-8 test demonstrated that the absorbance (A) value at 450 nm was significantly lower in IL-6R antibody group than in PMMA group and control group (P<0.01), but there was no statistically significant difference in A value at 450 nm between the control group and PMMA group (P>0.05). Results of ELISA indicated that the expression of OPG was significantly higher in IL-6R antibody group than in PMMA group and control group (P<0.01). The expression of RANKL was inhibited (P<0.05), and the ratio of OPG/RANKL was significantly increased in IL-6R antibody group as compared with PMMA group and control group. There was no significant difference in the expression of OPG between control group and PMMA group (P>0.05), but the expression of RANKL was higher in PMMA group than in control group (P<0.05), and there was a significant difference in the ratio of OPG/RANKL between them (P<0.05). Results of FQ-PCR revealed the expression of RANKL mRNA was significantly inhibited (P<0.01) and the expression of OPG mRNA was significantly increased (P<0.01) in IL-6R antibody group as compared with PMMA group and control group. The expression of RANKL mRNA was higher in PMMA group than in control group (P<0.05), but the expression of OPG mRNA had no significant difference between them (P>0.05). IL-6R antibody could significantly increase the expression of OPG, but inhibit the expression of RANKL, which might provide a theoretical basis of molecular biology for the prevention and treatment of aseptic loosening of prosthesis.

[Study on NaOH improving the surface morphology of three-dimensional printed poly- L- lactic acid mesh scaffolds].

Objective: To explore the effect of NaOH on the surface morphology of three-dimensional (3D) printed poly- L-lactic acid (PLLA) mesh scaffolds. Methods: The 3D printed PLLA mesh scaffolds were prepared by fused deposition molding technology, then the scaffold surfaces were etched with the NaOH solution. The concentrations of NaOH solution were 0.01, 0.1, 0.5, 1.0, and 3.0 mol/L, and the treatment time was 1, 3, 6, 9, and 12 hours, respectively. There were a total of 25 concentration and time combinations. After treatment, the microstructure, energy spectrum, roughness, hydrophilicity, compressive strength, as well as cell adhesion and proliferation of the scaffolds were observed. The untreated scaffolds were used as a normal control. Results: 3D printed PLLA mesh scaffolds were successfully prepared by using fused deposition molding technology. After NaOH etching treatment, a rough or micro porous structure was constructed on the surface of the scaffold, and with the increase of NaOH concentration and treatment time, the size and density of the pores increased. The characterization of the scaffolds by energy dispersive spectroscopy showed that the crystal contains two elements, Na and O. The surface roughness of NaOH treated scaffolds significantly increased ( P<0.05) and the contact angle significantly decreased ( P<0.05) compared to untreated scaffolds. There was no significant difference in compressive strength between the untreated scaffolds and treated scaffolds under conditions of 0.1 mol/L/12 h and 1.0 mol/L/3 h ( P>0.05), while the compression strength of the other treated scaffolds were significantly lower than that of the untreated scaffolds ( P<0.05). After co-culturing the cells with the scaffold, NaOH treatment resulted in an increase in the number of cells on the surface of the scaffold and the spreading area of individual cells, and more synapses extending from adherent cells. Conclusion: NaOH treatment is beneficial for increasing the surface hydrophilicity and cell adhesion of 3D printed PLLA mesh scaffolds.

IL-4-loaded alginate/chitosan multilayer films for promoting angiogenesis through both direct and indirect means.

Vascularization remains a major challenge in tissue engineering. In tissue repair with the involvement of biomaterials, both the material properties and material-induced immune response can affect angiogenesis. However, there is a scarcity of research on biomaterials that modulate angiogenesis simultaneously from both perspectives. Meanwhile, the effects and mechanisms of biomaterial-induced macrophages on angiogenesis remain controversial. In this study, a cytokine-controlled release system from our previous work was employed, and the effects thereof on angiogenesis through both direct and indirect means were investigated. Alginate/chitosan multilayer films were fabricated on interleukin (IL)-4-loaded titania nanotubes to achieve a sustained release of IL-4. The released IL-4 and the multilayers synergistically promoted angiogenic behaviors of endothelial cells (ECs), while up-regulating the expression of early vascular markers. Furthermore, polarized macrophages (both M1 and M2) notably elevated the expression of late vascular markers in ECs via the high expression of pro-maturation factor angiogenin-1. After subcutaneous implantation, the IL-4-loaded implants induced increased neovascularization in a short period, with the surrounding tissue returning to normal at the later stage. Therefore, the proposed IL-4-loaded implants exhibited superior pro-angiogenic capability in vitro and in vivo through both direct stimulation of ECs and the indirect induction of a suitable immune microenvironment.

Corrosion-tailoring, osteogenic, anti-inflammatory, and antibacterial aspirin-loaded organometallic hydrogel composite coating on biodegradable Zn for orthopedic applications.

Zn and its alloys are receiving increasing interest for biodegradable orthopedic implant applications owing to their moderate corrosion rate and the potential functionality of Zn2+. However, their non-uniform corrosion behavior and insufficient osteogenic, anti-inflammatory, and antibacterial properties do not meet the comprehensive requirements of orthopedic implants in clinical use. Herein, an aspirin (an acetylsalicylic acid, ASA, 10, 50, 100, and 500 mg/L)-loaded carboxymethyl chitosan (CMC)/gelatin (Gel)-Zn2+ organometallic hydrogel composite coating (CMC/Gel&Zn2+/ASA) was fabricated on a Zn surface via an alternating dip-coating method, aiming to obtain a material with these comprehensive properties improved. The organometallic hydrogel composite coatings, ca. 12-16 µm in thickness, showed compact, homogeneous, and micro-bulge structured surface morphology. The coatings protected well the Zn substrate from pitting/localized corrosion and contained the release of the bioactive components, Zn2+ and ASA, in a sustained and stable manner in long-term in vitro immersions in Hank's solution. The coated Zn showed greater ability to promote proliferation and osteogenic differentiation for MC3T3-E1 osteoblasts, and better anti-inflammatory capacity when compared with uncoated Zn. Additionally, this coating displayed excellent antibacterial activity against both Escherichia coli (>99 % antibacterial rate) and Staphylococcus aureus (>98 % antibacterial rate). Such appealing properties can be attributed to the compositional nature of the coating, namely the sustained release of Zn2+ and ASA, as well as the surface physiochemical properties because of its unique microstructure. This organometallic hydrogel composite coating can be considered a promising option for the surface modification of biodegradable Zn-based orthopedic implants among others.

Tibial plateau fracture and RNA sequencing with osteogenesis imperfecta: a case report.

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis. Case presentation: A 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)-receptor interactions. Conclusion: In this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.

Metal-organic Zn-zoledronic acid and 1-hydroxyethylidene-1,1-diphosphonic acid nanostick-mediated zinc phosphate hybrid coating on biodegradable Zn for osteoporotic fracture healing implants.

Zn and its alloys are increasingly under consideration for biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for osteoporotic bone fracture healing, due to their uneven degradation mode, burst release of zinc ions, and insufficient osteo-promotion and osteo-resorption regulating properties. In this study, a type of Zn2+ coordinated zoledronic acid (ZA) and 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) metal-organic hybrid nanostick was synthesized, which was further mixed into zinc phosphate (ZnP) solution to mediate the deposition and growth of ZnP to form a well-integrated micro-patterned metal-organic/inorganic hybrid coating on Zn. The coating protected noticeably the Zn substrate from corrosion, in particular reducing its localized occurrence as well as suppressing its Zn2+ release. Moreover, the modified Zn was osteo-compatible and osteo-promotive and, more important, performed osteogenesis in vitro and in vivo of well-balanced pro-osteoblast and anti-osteoclast responses. Such favorable functionalities are related to the nature of its bioactive components, especially the bio-functional ZA and the Zn ions it contains, as well as its unique micro- and nano-scale structure. This strategy provides not only a new avenue for surface modification of biodegradable metals but also sheds light on advanced biomaterials for osteoporotic fracture and other applications. STATEMENT OF SIGNIFICANCE: Developing appropriate biodegradable metallic materials is of clinical relevance for osteoporosis fracture healing, whereas current strategies are short of good balance between the bone formation and resorption. Here, we designed a micropatterned metal-organic nanostick mediated zinc phosphate hybrid coating modified Zn biodegradable metal to fulfill such a balanced osteogenicity. The in vitro assays verified the coated Zn demonstrated outstanding pro-osteoblasts and anti-osteoclasts properties and the coated intramedullary nail promoted fracture healing well in an osteoporotic femur fracture rat model. Our strategy may offer not only a new avenue for surface modification of biodegradable metals but also shed light on better understanding of new advanced biomaterials for orthopedic application among others.

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/ß-Catenin Signaling Pathway.

In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, ß-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, ß-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/ß-catenin signaling pathway.

An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment.

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1ß-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.