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.
Fibrous hydrogel scaffolds have recently attracted increasing attention for tissue engineering applications. While a number of approaches have been proposed for fabricating microfibers, it remains ...difficult for current methods to produce materials that meet the essential requirements of being simple, flexible and bio-friendly. It is especially challenging to prepare cell-laden microfibers which have different structures to meet the needs of various applications using a simple device. In this study, we developed a facile two-flow microfluidic system, through which cell-laden hydrogel microfibers with various structures could be easily prepared in one step. Aiming to meet different tissue engineering needs, several types of microfibers with different structures, including single-layer, double-layer and hollow microfibers, have been prepared using an alginate-methacrylated gelatin composite hydrogel by merely changing the inner and outer fluids. Cell-laden single-layer microfibers were obtained by subsequently seeding mouse embryonic osteoblast precursor cells (MC3T3-E1) cells on the surface of the as-prepared microfibers. Cell-laden double-layer and hollow microfibers were prepared by directly encapsulating MC3T3-E1 cells or human umbilical vein endothelial cells (HUVECs) in the cores of microfibers upon their fabrication. Prominent proliferation of cells happened in all cell-laden single-layer, double-layer and hollow microfibers, implying potential applications for them in tissue engineering.
Repairing large segmental bone defects above a critical size remains challenging with high risk of delayed union or even non-union. From the perspective of bone development and clinical experience, ...periosteum plays an indispensable role in bone repair and reconstruction. In this study, we explored the feasibility of using preosteoblast-derived matrix (pODM) as a biomimetic periosteum. By culturing MC3T3-E1 cell sheet on poly(dimethylsiloxane) and performing decellularization, an integral cell-free sheet of pODM could be readily harvested. Bone marrow mesenchymal stem cells (BMSCs) adhered and proliferated well on pODM. In addition, pODM exhibited a chemotactic effect on BMSCs in a concentration-dependent manner and also promoted osteogenic differentiation of BMSCs. Following that, pODM was wrapped around a gelatin methacryloyl (GelMA) hydrogel to construct an engineered periosteum-bone substitute. A rabbit radius segmental bone defect model was used to examine the bone repair efficacy of pODM/GelMA. Upon implantation of pODM/GelMA construct for 12 weeks, the critical-sized bone defects completely healed with remarkable full reconstruction of medullary cavity at the radial diaphysis. Together, this work proposes a high potency of using precursor cell-derived matrix as a biomimetic periosteum, which preserves the beneficial biological factors while avoids the limitations of using exogenous cells for bone regeneration. Combining precursor cell-derived matrix with hydrogel may provide a promising periosteum-bone biomimetic substitute for bone repair. STATEMENT OF SIGNIFICANCE: Repairing large segmental bone defects above a critical size remains challenging. As the periosteum plays an essential role in bone repair, this study aimed to explore the use of preosteoblast-derived matrix (pODM), harvested from decellularized MC3T3-E1 cell sheet, as a biomimetic periosteum to facilitate bone repair. We found that in vitro, pODM exhibited considerable chemotactic effect and osteogenic induction capability to bone marrow mesenchymal stem cells (BMSCs). In vivo, implantation of pODM/gelatin methacryloyl (GelMA) constructs as engineered periosteum-bone substitutes effectively repaired the critical-sized segmental bone defects at rabbit radius. Surprisingly, remarkable full reconstruction of medullary cavity at the diaphysis was achieved. Therefore, combining pODM with hydrogel may provide a promising biomimetic substitute for bone repair.
Cell sheet-based scaffold-free technology holds promise for tissue engineering applications and has been extensively explored during the past decades. However, efficient harvest and handling of cell ...sheets remain challenging, including insufficient extracellular matrix content and poor mechanical strength. Mechanical loading has been widely used to enhance extracellular matrix production in a variety of cell types. However, currently, there are no effective ways to apply mechanical loading to cell sheets. In this study, we prepared thermo-responsive elastomer substrates by grafting poly(N-isopropyl acrylamide) (PNIPAAm) to poly(dimethylsiloxane) (PDMS) surfaces. The effect of PNIPAAm grafting yields on cell behaviours was investigated to optimize surfaces suitable for cell sheet culturing and harvesting. Subsequently, MC3T3-E1 cells were cultured on the PDMS-g-PNIPAAm substrates under mechanical stimulation by cyclically stretching the substrates. Upon maturation, the cell sheets were harvested by lowering the temperature. We found that the extracellular matrix content and thickness of cell sheet were markedly elevated upon appropriate mechanical conditioning. Reverse transcription quantitative polymerase chain reaction and Western blot analyses further confirmed that the expression of osteogenic-specific genes and major matrix components were up-regulated. After implantation into the critical-sized calvarial defects of mice, the mechanically conditioned cell sheets significantly promoted new bone formation. Findings from this study reveal that thermo-responsive elastomer, together with mechanical conditioning, can potentially be applied to prepare high-quality cell sheets for bone tissue engineering.
The positive role of hydropower in climate change adaption is well accepted by the international community and has been highlighted many times, while the understanding of its impacts on socioeconomic ...development remains at the stage of rough estimation and qualitative description. The application of a multi-regional CGE model in this paper provides an effective tool for quantitatively assessing the socioeconomic impacts of hydropower development, reflecting its positive functions. This case study on the Upper Chuan River details the steps of model development, including impact mechanism analysis, regional de- limitation, macro closure setting, shock selection, and database preparation. The results show the enormous economic benefits of hydropower development using various indicators such as consumption, investment, GDP, employment, and income. The study indicates that hydropower development is a win-win energy development mode which can help to realize the integration of sustainable development and climate change mitigation. Finally, potential improvements to the model are discussed.
China's urbanization is rapidly proceeding while bringing marked impact on the energy consumption. This paper contributes to current literature by using an improved spatial econometric model ...Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) to investigate the effect of urbanization on energy consumption for China's regions. The impact of urbanization is further disaggregated into direct and indirect impacts from the perspective of spatial econometrics. Results show that, if the urbanization level increases by 1.0%, energy consumption levels will correspondingly decrease by 0.089%. The spatial spillover effect on adjacent areas is positive: a 1.0% increase in one specific area's urbanization level leads to a 0.136% increase in an adjacent area's energy consumption. It is suggested that, it is essential to devote major efforts to energy conservation, in the process of improving the new-type urbanization. In particular, disaggregating China's targets for controlling energy consumption into smaller targets for different regions will contribute to controlling the growth of energy consumption.
Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis ...in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.
MicroRNAs (miRNAs) play important roles in tumorigenesis and tumor progression. In this study, we investigated the role of miR-320a-3p in non-small cell lung cancer (NSCLC). Expressions of ...miR-320a-3p were firstly determined in 80 NSCLC patients' cancer tissues and adjacent normal lung tissues by qRT-PCR. Then MTT assay, cell migration and invasion assays were performed in vitro. Potential binding sites on target gene of miR-320a-3p were predicted and luciferase reporter assay was used to identify the potential binding sites. Tumorigenesis assay were performed in nude mice by injecting A549 cells which stably express miR-320a-3p. Results indicated that high expression of miR-320a-3p suppresses cell proliferation, migration and invasion through the inactivation of PI3K/Akt signaling pathway in NSCLC cells. Smaller tumor size and lighter weight were also found in nude mice which had miR-320a-3p higher expressed. Furthermore, data from luciferase reporter assay proved the direct binding of miR-320a-3p on the 3′UTR region of ELF3 mRNA, this could further decrease ELF3 expression transcriptionally. We provided evidence that miR-320a-3p might work as a tumor suppressor in NSCLC both in vivo and in vitro.
Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis ...in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-alpha) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-alpha and remarkably reduced levels of MUC1 in RSV-infected and TNF-alpha treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBalpha and MUC1 in TNF-alpha-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.
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