Safe and efficient gene therapy is highly desired for controlling pathogenic fibrosis of nucleus pulposus (NP) tissue, which would result in intervertebral disc (IVD) degeneration and disability if left untreated. In this work, a hyperbranched polymer (HP) with high plasmid DNA (pDNA) binding affinity and negligible cytotoxicity is synthesized, which can self-assemble into nano-sized polyplexes with a “double shell” structure that can highly efficiently transfect pDNA into NP cells. These polyplexes are then encapsulated in biodegradable nanospheres (NS) to enable two-stage delivery: 1) temporally-controlled release of pDNA-carrying polyplexes and 2) highly efficient delivery of pDNA into cells by the released polyplexes. These biodegradable NS are co-injected with nanofibrous spongy microspheres (NF-SMS) to localize the cellular transfection of the pDNA encoding orphan nuclear receptor 4A1 (NR4A1), which was recently reported as a therapeutic agent to delay pathogenic fibrosis. It is shown that HP can transfect human NP cells efficiently in vitro with low cytotoxicity. The two-stage delivery system is able to present the polyplexes over a sustained time period (more than 30 days) in the tail of rat. The NR4A1 pDNA carried by the HP polyplexes is found to therapeutically reduce the pathogenic fibrosis of NP tissue in a rat-tail degeneration model. In conclusion, the combination of the two-stage NR4A1 pDNA delivery NS and NF-SMS is able to repress fibrosis and to support IVD regeneration.
OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. This paper focuses on the adherence during ageing of a primer (made of polyester resins crosslinked with melamine) applied onto hot-dip galvanized (HDG) steel for coil coating application and its influence on corrosion protection. A chromium-free surface treatment, composed of fluorotitanic acid, phosphoric acid, manganese phosphate, and vinylphenol was applied on the HDG steel to obtain high corrosion resistance and high adherence of a polyester and melamine primer. The influence of the manganese phosphate on the corrosion and adherence was investigated. To measure the adherence between the metal and the primer, a three-point flexure test was set up. The adherence was then linked with corrosion resistance during ageing, using electrochemical impedance spectroscopy.
Tissue engineering has shown great promise in developing novel therapies for treating injured tissue and organ failure. Scaffolds play a pivotal role in tissue engineering. Biodegradable polymers are the primary choice of material for tissue engineering scaffolds, due to their numerous advantageous properties. In this article, the principles of tissue engineering are discussed in relation to polymer science and engineering. The most frequently used polymers in tissue engineering are briefly reviewed. These include synthetic and natural polymers commonly used in constructing both porous and hydrogel scaffolds. Their structure and critical properties in relation to scaffold function are discussed in depth, along with a detailed review of the important roles functionalized materials and controlled release play in tissue engineering. Important polymer processing techniques in the context of scaffold fabrication are also reviewed. These include the textile technologies, electrospinning, particulate‐leaching techniques, phase‐separation techniques, rapid prototyping, and other novel three‐dimensional (3D) fabrication techniques. In this update, the impact of pluripotent stem cells, conductive polymers, controlled drug release, 3D printing, and nanofibrous topology on tissue engineering are also discussed.
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