Exploring innovative solutions to improve the healthcare of the aging and diseased population continues to be a global challenge. Among a number of strategies toward this goal, tissue engineering and ...regenerative medicine (TERM) has gradually evolved into a promising approach to meet future needs of patients. TERM has recently received increasing attention in Asia, as evidenced by the markedly increased number of researchers, publications, clinical trials, and translational products. This review aims to give a brief overview of TERM development in Asia over the last decade by highlighting some of the important advances in this field and featuring major achievements of representative research groups. The development of novel biomaterials and enabling technologies, identification of new cell sources, and applications of TERM in various tissues are briefly introduced. Finally, the achievement of TERM in Asia, including important publications, representative discoveries, clinical trials, and examples of commercial products will be introduced. Discussion on current limitations and future directions in this hot topic will also be provided.
Despite great progress made in developing orthopedic implants, the development of titanium (Ti) implants with ideal early osseointegration remains a big challenge. Our pilot study has demonstrated ...that Si-TiO
nanotubes on the surface of Ti substrates could enhance their osteogenic activity. Hence, in this study, we aim to comprehensively evaluate the effects of silicon-doped titania (Si-TiO
) nanotubes on the osseointegration property of Ti implants.
The Ti implants were surface modified with Si-TiO
nanotubes through in situ anodization and Si plasma immersion ion implantation (PIII) method. Three groups were divided as Ti implants (Ti), Ti modified with TiO
nanotubes (TiO
-NTs) and Ti modified with Si-TiO
nanotubes (Si-TiO
-NTs). The morphology of Si-TiO
nanotubes was observed by scanning electron microscope. The growth and osteogenic differentiation of MC3T3-E1 cells on the Ti implants were evaluated. Further, the pull-out tests and in vivo osseointegration ability evaluation were performed after implanting the screws in the femur of Sprague Dawley rats.
The Si-TiO
nanotubes could be seen on the surface of Ti implants. The MC3T3-E1 cells could grow on the surface of Ti, TiO
-NTs and Si-TiO
-NTs, and showed fast proliferation rate on the Si-TiO
-NTs. Moreover, the production of some osteogenesis-related proteins (ALP and Runx2) at one week and calcium deposition at four week was also enhanced in Si-TiO
-NTs rather than other groups. In vivo osseointegration results showed that Si-TiO
nanotube-modified Ti screws had higher pullout force at two and four weeks as well as enhanced new bone formation at six weeks compared to bare Ti screws and Ti screws modified with TiO
nanotubes alone.
The modification of Si-TiO
-NTs on the Ti substrate could generate a nanostructured and hydrophilic surface, which can promote cell growth. Moreover, the existence of the TiO
nanotubes and Si element also can improve the in vitro osteogenic differentiation of MC3T3-E1 cells and early bone formation around the implanted screws. Together, findings from this study show that surface modification of Ti implants with Si-TiO
nanotubes could enhance early osseointegration and therefore has the potential for clinical applications.
Calcium phosphate cement (CPC), which exhibits excellent biocompatibility and bioactivity, is a well-established material for the repair of bone defects. However, its disadvantages such as poor ...washout resistance and low mechanical strength limit its clinical applications. In this study, CPC with enhanced washout resistance and mechanical properties has been developed by the in situ crosslinking of glycidyl methacrylate modified γ-polyglutamic acid (m-PGA) within the cement matrix, forming an interpenetrating network. Compared with unmodified CPC, the final setting time of the composite cements was shortened and its washout resistance was significantly improved. In addition, the composite cements showed enhanced mechanical strength and degradation properties. An in vitro study demonstrated that the composite cements exhibited good biocompatibility. The in vivo results showed that the composite cements promoted bone formation. These results suggest that the biocompatible, injectable α-tricalcium phosphate (α-TCP)/m-PGA cements may have the potential to be used as bone filling materials for future clinical applications.
Brushite cements have good osteoconductive and resorbable properties, but the low mechanical strength and poor injectability limit their clinical applications in load-bearing conditions and minimally ...invasive surgery. In this study, an injectable brushite cement that contains monocalcium phosphate monohydrate (MCPM) and β-tricalcium phosphate (β-TCP) as its solid phase and ammonium ferric citrate (AFC) solution as the aqueous medium was designed to have high mechanical strength. The optimized formulation achieved a compressive strength of 62.8 ± 7.2 MPa, which is above the previously reported values of hand-mixing brushite cements. The incorporation of AFC prolonged the setting times and greatly enhanced the injectability and degradation properties of the cements.
and
experiments demonstrated that the brushite cements exhibited good biocompatibility and bone regeneration capacity. The novel brushite cement is promising for bone healing in load-bearing applications.
Mechanical cues from the extracellular matrix (ECM) microenvironment are known to be significant in modulating the fate of stem cells to guide developmental processes and maintain bodily homeostasis. ...Tissue engineering has provided a promising approach to the repair or regeneration of damaged tissues. Scaffolds are fundamental in cell-based regenerative therapies. Developing artificial ECM that mimics the mechanical properties of native ECM would greatly help to guide cell functions and thus promote tissue regeneration. In this review, we introduce various mechanical cues provided by the ECM including elasticity, viscoelasticity, topography, and external stimuli, and their effects on cell behaviours. Meanwhile, we discuss the underlying principles and strategies to develop natural or synthetic biomaterials with different mechanical properties for cellular modulation, and explore the mechanism by which the mechanical cues from biomaterials regulate cell function toward tissue regeneration. We also discuss the challenges in multimodal mechanical modulation of cell behaviours and the interplay between mechanical cues and other microenvironmental factors.
Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform ...single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.
Long non-coding RNAs (lncRNAs), as one of the components of exosomes derived from cancer-associated fibroblasts (CAFs), exhibit a crucial role in the pathogenesis and chemoresistance of gastric ...cancer (GC). Herein, we investigated the role and mechanism of a novel lncRNA disheveled binding antagonist of beta catenin3 antisense1 (DACT3-AS1) and its involvement in GC.
DACT3-AS1 was identified by RNA-sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The functional role of DACT3-AS1 in GC was evaluated using in vitro and in vivo experiments including Transwell assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay, immunoblotting, and xenograft tumor mouse model. Dual-luciferase reporter assay was performed to assess the association between genes.
DACT3-AS1 was downregulated and involved in poor prognosis of patients with GC. The results from both in vitro and in vivo experiments showed that DACT3-AS1 suppressed cell proliferation, migration, and invasion through targeting miR-181a-5p/sirtuin 1 (SIRT1) axis. Additionally, DACT3-AS1 was transmitted from CAFs to GC cells mainly via exosomes. Exosomal DACT3-AS1 alleviated xenograft tumor growth. DACT3-AS1 conferred sensitivity of cancer cells to oxaliplatin through SIRT1-mediated ferroptosis both in vitro and in vivo.
CAFs-derived exosomal DACT3-AS1 is a suppressive regulator in malignant transformation and oxaliplatin resistance. DACT3-AS1 could be used for diagnosis and treatment of GC.
Based on real-world medical data, the artificial neural network model was used to predict the risk factors of linezolid-induced thrombocytopenia to provide a reference for better clinical use of this ...drug and achieve the timely prevention of adverse reactions.
The artificial neural network algorithm was used to construct the prediction model of the risk factors of linezolid-induced thrombocytopenia and further evaluate the effectiveness of the artificial neural network model compared with the traditional Logistic regression model.
A total of 1,837 patients receiving linezolid treatment in a hospital in Xi 'an, Shaanxi Province from 1 January 2011 to 1 January 2021 were recruited. According to the exclusion criteria, 1,273 cases that did not meet the requirements of the study were excluded. A total of 564 valid cases were included in the study, with 89 (15.78%) having thrombocytopenia. The prediction accuracy of the artificial neural network model was 96.32%, and the AUROC was 0.944, which was significantly higher than that of the Logistic regression model, which was 86.14%, and the AUROC was 0.796. In the artificial neural network model, urea, platelet baseline value and serum albumin were among the top three important risk factors.
The predictive performance of the artificial neural network model is better than that of the traditional Logistic regression model, and it can well predict the risk factors of linezolid-induced thrombocytopenia.
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