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Microstructures bioactives par électroimpression voie solvant pour la régénération tissulaire

Abstract : Direct-writing electrospinning is a recent technique able to deposit fibers with a stable polymer jet on a moving collector similarly to additive manufacturing. The aim of this work was to develop the solvent-based direct-writing electrospinning technique and produce bioactive structures for tissue engineering applications. A first fundamental study have been carried out on the stability mechanism of the polymer jet under electric field. This study showed that stable jet without whipping behavior could be obtained by increasing polymer concentration or molecular weight and thus viscoelasticity. Those results give rise to a new strategy to optimize solution formulation and enlarge the number of materials used for direct-writing electrospinning. Mechanism of filaments stacking have also been studied in order to find solutions to produce higher organized structure without stacking defects. Preliminary tests showed that injection of humidified air, ionized air or the use of two polarities could reduce the number of stacking defects. Protection and release of protein from electrospun filaments is still a current challenge for tissue engineering. Then, different polymer formulation with a model protein, bovine serum albumin (BSA), was tested to find a way to preserve the protein. Secondary structure of bovine serum albumin (BSA) was investigated by circular dichroism to check protein activity. Released BSA in water from poly (lactic-co-glycolic acid) (PLGA) filament had a similar structure to its native one which means that electrospinning had a relatively low effect on BSA structure or that BSA show good structure reversibility. The kinetic release of BSA from PLGA filaments also showed that the presence of poly (ethylene glycol) (PEG) allow a higher amount of BSA to be released. The bioactive potential of filaments containing growth factors was tested for a hepatic and periodontal regeneration. The hepatic regenerative potential of PLGA filaments containing hepatocyte growth factors (HGF) could not been tested but a reproducible effect was noticed on hepatocyte cells HepG2 according to the amount of HGF in the filaments. Concerning the periodontal regeneration, periodontal ligament cells (PDLC) was cultured on different organized structures: a composite one made of poly (caprolactone) (PCL) and hydroxyapatite nanoparticles and the other one is made of core-shell PEG-PCL filaments containing cementum protein 1 (CEMP1). The two structures allowed the PDLC to produce a mineralized matrix which was not the case for the two other structures without nanoparticles and CEMP1. Thus, those bioactive structures showed promising regenerative potential for hard tissues like bone or cement.
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Submitted on : Thursday, February 13, 2020 - 2:52:10 PM
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Laura Bourdon. Microstructures bioactives par électroimpression voie solvant pour la régénération tissulaire. Matériaux. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1244⟩. ⟨tel-02477598⟩

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