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Experiments on the transport of radiolabeled Insulin-like Growth Factors (IGF-I and -II) into bovine articular cartilage show differential uptake depending on the relative proportion of IGF-I and -II. In this study, we present a mathematical model describing both the transport and competition of IGF-I and -II for binding sites represented by two functional groupings of IGF binding proteins (IGFBPs). The first grouping has approximately similar binding affinity to both IGF-I and -II (i.e. IGFBPs 1–5), whereas the second group has significantly higher binding preference for IGF-II compared to IGF-I (i.e. IGFBP-6). Using nonlinear least squares, it is shown that the experimental equilibrium competitive binding results can be described using a reversible Langmuir sorption isotherm involving two dominant IGFBP functional groups.
After coupling the sorption model with a poromechanical continuum model, parametric studies are carried out to investigate the effect of model changes including IGF boundary conditions and the ratios of the two IGFBP functional groups. The results show that ignoring competitive binding leads to a significant overestimation of total IGF-I uptake, but an underestimation the rate of "free" (physiologically active) IGF-I within the cartilage. An increase of first group of IGFBPs (i.e. IGFBPs 1–5) as has been reported for osteoarthritis, is observed to hinder the bioavailability of free IGF-I in cartilage, even though the total IGF-I uptake is enhanced. Furthermore, the combination of dynamic compression and competitive binding is seen to enhance the IGF-I uptake within cartilage, but this enhancement is overestimated if competitive binding is neglected.
The article is about the tissue engineering research done in China. It discusses various aspects of tissue engineering in China including engineered bones, cartilage, skin, corneal stroma and blood vessels.
The article is about the tissue engineering laboratory in Malaysia. It touches on six areas of bioengineering, namely: skin, cartilage, bone, respiratory epithelium, stem cells and biomaterials.
AUSTRALIA – Australia's First Full Genome Project to be Conducted on Corals.
AUSTRALIA – Scientists May have Discovered New Potential Cure for Cancer.
AUSTRALIA – First Genetically-engineered Malaria Vaccine To Enter Human Trials.
CHINA – Lead Poisoning Sickens 600 Kids in China.
CHINA – Groundbreaking Treatment for Oxygen-deprived Newborns.
CHINA – China Builds First Heavy Ion Therapy Center for Cancer Patients.
CHINA – Creating Live Mice from Skin Cells.
INDIA – Human Clinical Trial in 2010 for Needle-free Measles Vaccination.
INDIA – Indian Wonder Herb can Treat Male Infertility.
JAPAN – Flood Resistant High-yield Rice Developed.
SINGAPORE – Minimally Invasive Option for Knee Cartilage Repair.
SINGAPORE – Novel Immunization Method for Malaria Offers Insights into Human Anti-Malaria Immune Response.
TAIWAN – Taiwan Researchers Identify Sites of Breast Cancer Genes.
TAIWAN – Taiwanese Researchers Develop Cell Therapy For Immunodeficiency.
TAIWAN – Remote Healthcare Services for High-risk Patients.
TAIWAN – Marine-derived Compounds Holds New Treatment Premise for Neuropathic Pain.
OTHER REGIONS — UNITED STATES – New No-needle Approach to Prevent Blood Clots.
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Major New Asean Health and Well-Being Study.
The First Chinese Laboratory Recognized By International Olive Council (IOC).
China Kicks off Precision Medicine Research.
Chinese Researchers Find Flavonoids in Cotton Petals to Treat Alzheimer's Disease.
China Recognizes Prominent Scientists and Stresses on Innovation.
China Corporation Tencent in Kenya to Help Combat Illegal Wildlife Trade.
Catalyst Helps Convert Waste CO2 into Fuel.
Articular Cartilage Stem Cells Participate in Cartilage Self-Repair during Early Osteoarthritis.
Chinese Scientists Develop Polygraph Based on AI Technology.
Scientists Uncover Beneficiary Effects of Dietary Iron Oxide Nanoparticles.
A New Water Robot “Born” to Detect Water Quality.
Archaeologists Discover World's Oldest Tea Buried with Ancient Chinese Emperor.
Scientists Find in situ KIT-expressing Cardiomyocytes.
Integrin CD11b Regulates Obesity-Related Insulin Resistance.
Asia's Medical Technology Start-ups Get New Fast Track to Market via Partnership between Cambridge Consultants and Clearbridge Accelerator
Mitsubishi Electric and Sembcorp Industries to Testbed Novel Ozone Backwashing Energy-Saving Membrane Bioreactor
LEO Pharma Enters Biologics through Strategic Partnership with AstraZeneca
Bayer and X-Chem Expand Drug Discovery Collaboration to Discover Novel Medicines
New Gas Chromatography System Brings Power of Orbitrap GC-MS Technology to Routine Applications
A*STAR and MSD Establish a New Research Collaboration to Advance Peptide Therapeutics
Stem Cells Engineered to Grow Cartilage, Fight Inflammation
Cartilage defects remain one of the most challenging musculoskeletal tissues to treat owing to its poor healing capacity. The lack of sufficient clinical treatments has led to a drive in tissue engineering advancements that combine chondrogenic cells with scaffolds to aid in cartilage regeneration. Nanoscale materials are commonly used in scaffold synthesis because of their ability to mimic the size of extracellular matrix (ECM). This review focuses on the use of nanostructured scaffolds in combination with cells for cartilage tissue engineering. We detail the fabrication methods and materials used to produce nanostructured scaffolds, with a focus on nanofibers and their role in modulating cell biology. Lastly, we discuss various techniques that further functionalize the nanostructured scaffolds to enhance cellular responses.
Polyhedral oligomeric silsesquioxane (POSS) based nanocompounds have recently emerged as viable compounds to make totally synthetic biocompatible tissue substitutes for use in the clinical arena. Here, we report on the use of three POSS based compounds to develop bionanohybrid scaffolds composed primarily of purified Type II collagen. The bionanohybrid scaffolds were prepared by blending purified Type II collagen with octa maleamic acid POSS, octa ammonium POSS, or polyethylene glycol POSS. We were able to differentially detect the presence of the different POSS compounds in the bionanohybrid scaffolds using attenuated total reflectance Fourier transformed infrared (ATR-FTIR) spectroscopy. The differential scanning calorimetry (DSC) characterized the effect of the hydrophilic POSS additives on the thermal behavior of the bionanohybrid scaffolds. Next, scanning electron microscopy revealed that different POSS compounds enhanced, refined, or altered the three-dimensional scaffold microstructure. Finally, by using these scaffolds to create three-dimensional tissue constructs, we measured the ability of human foreskin fibroblasts to migrate out and proliferate into the biomaterials. Our data suggest that POSS can be incorporated with native polymeric structural proteins to influence biomaterial architecture where cells can migrate and proliferate.
Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.
Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.
Maintenance of differentiated functional phenotype within in vitro chondrocyte culture requires seeding at high densities with large numbers of cells. However, optimal cell seeding numbers and densities remain elusive due to multiple varying parameters and different methodologies utilized in previous studies. In the current study, we tried to investigate the relationship between cell seeding number and differentiated functional phenotype of in vitro cultured chondrocytes. Varying numbers of primary porcine chondrocytes (0.25, 2.5, 25 and 250 K) were seeded in 96 well-plates and cultured for 4 weeks. Cell proliferation, glycosaminoglycan (GAG) production and gene expression levels of Sox9, aggrecan, COL II and COL I were evaluated. The results showed that GAG content was high in the 0.25 and 25 K groups, gene expression of Sox9 was high in the 2.5, 25 and 250 K groups and expression of COL II was high in the 25 K group, whereas expression of COL I was low in the 0.25, 25 and 250 K groups. It is concluded that the seeding number and density of the 25 K (78 K cells/cm2) group achieved the optimal balance between functional phenotype of individual cells and the total ECM production for in vitro cultured chondrocytes.
Tissue engineering can be broadly defined as the combination of biology and engineering to repair or replace lost tissue function. From an industry perspective, the field encompasses implanted biomaterials, cell and tissue transplants and therapies, and even extracorporeal cellular devices. To achieve its goals, tissue engineering must effectively utilize not only multiple aspects of engineering but also several aspects of biology that govern mechanisms of organ development, repair and regeneration. The field has always had a strong focus on application yet the challenge of integrating biological science, engineering and medicine has kept many past efforts from reaching their therapeutic and commercial potential. This chapter covers the evolution of tissue engineering, looking at the change in emphasis from bioengineering to stem cell biology and the potential impact of this shift in focus from an industrial perspective. In addition, we have analyzed four major commercial thrusts from past to present: vascular tissue engineering, cartilage repair, liver-assist devices and skin constructs, paying particular attention to how the biomedical disciplines must be integrated to achieve commercial feasibility and therapeutic success. Each example yields one or more important and practical lessons learnt that could be instructive for most future medical and commercial efforts in tissue engineering.
In vivo animal models are currently the gold standard for testing the capacity of stem/progenitor cells, smart biomaterials and novel growth factors for successful tissue engineering. In vitro models ultimately fail to provide the appropriate physiologically relevant microenvironment and hence animal models are an essential pre-requisite in the translation of any new therapy to the clinic. The aim of this chapter is to consider the available animal models commonly in use for tissue engineering, with a particular focus upon bone and cartilage research. Factors driving the choice of a given animal model are reviewed, according to the requirements of experimental design, hypothesis and the specific parameters to be tested. A number of animal models, together with their respective advantages and limitations are described, ranging from relatively simple experimental designs such as the subcutaneous implant and muscle pouch models, through to the diffusion chamber model and chorioallantoic membrane assay, to the more complex in vivo bioreactors and (arguably the most clinically relevant) bone and cartilage defect models. The need to consider the ethical issues of using animal models and the principles of reduction, replacement and refinement are emphasised in selecting the final experimental model of choice.
The most exciting discoveries in the last two decades have been the mapping, sequencing, and understanding of genes in our body. In this chapter, we will discuss how to specifically map expression profiles of gene products — mRNA, protein, and reporter gene (X-gal) — using in situ hybridization, immunohistochemistry, and X-gal staining, respectively.
Cartilage damage is irreversible due to its properties of avascularity and lack of undifferentiated cells. Studying the biology of chondrocytes and cartilage is therefore critical to understand the underlying mechanism and to explore the potential repair approaches. It has been reported that three-dimensional (3D) chondrocyte culture behaves very differently from two-dimensional (2D) monolayer culture. Therefore, a native 3D culture of chondrocytes is valuable for such a research purpose, and may also be an option for repairing cartilage defects. This chapter describes a detailed protocol for high-yield chondrocyte isolation and the modified pellet culture technique (using a 3D chondrocyte culture), which can synthesize a bioengineered tissue up to 8 mm in diameter. The authors aim at providing a platform for researchers to study chondrocyte behavior in a 3D environment and to explore the application of scaffold-free tissue for transplantation into a large cartilage defect model.
Perhaps the most difficult task in bone histology work is the preparation of a good specimen. It is impossible to obtain a good image of bone or cartilage without careful preparation and processing of specimens. This chapter will describe very basic skills in the preparation of specimens. These techniques include the paraffin method, plastic method, and frozen method.
Bone or cartilage cells are essentially colorless, and it is difficult to distinguish their morphologies under a light microscope. To better visualize these structures, various staining techniques have been developed; due to page constraints, we will only describe the most common methods for readers. These staining assays include hematoxylin and eosin (H&E) stain, used for general histology of the cell; Safranin O stain, used for the cartilage; and von Kossa and van Gieson stains as well as modified Goldner's trichrome stain, used for nondecalcified tissues.
Attrition and eventual loss of articular cartilage are crucial elements in the pathophysiology of osteoarthritis. Preventing the breakdown of cartilage is believed to be critical in order to preserve the functional integrity of a joint. Magnetic resonance imaging (MRI) and advanced digital postprocessing techniques have opened novel possibilities for in vivo quantitative analysis of cartilage morphology, structure, and function in health and disease. Techniques of semiquantitative scoring of human knee cartilage pathology and quantitative assessment of human cartilage have recently been developed. Though cartilage represents a thin layer of material relative to the size of voxels typically used for MRI, cartilage thickness and volume have been quantified in human and in small animals. MRI-detected cartilage loss has been shown to be more sensitive than radiography-detected joint space narrowing. Progress made in MRI technology in the last few years allows longitudinal studies of knee cartilage with an accuracy good enough to follow disease-caused changes and to evaluate the therapeutic effects of chondroprotective drugs.
Articular cartilage is hyaline cartilage which has very limited self-repairingcapacity after its degeneration or injury. Recently, three-dimensional (3D) bioprinting provides a promising method for repair and regeneration of articular cartilage. Significant progress has been made in 3D bioprinting for cartilage regeneration, particularly in printing hydrogels in combination of cells and growth factors. In this chapter, we reviewed recent progress in cartilage 3D bioprinting, including the use of various cell sources and growth factors for cartilage formation. We also discussed the challenges and the future research directions of cartilage regeneration.
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