http://www.cermav.cnrs.fr

Rachel Auzély-VeltyGrenoble Alpes University and Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), Grenoble, France

1

Functional polysaccharide materials: fromsynthesis to biomedical applications

Hydrogels for tissue engineering and cell therapy Drug delivery micro- et nanosystems

(cancer, diabetes, leishmania treatment)

10 µm

Patterned hydrogels for cell culture

Nanoparticle-hydrogel composites as patches

for drug delivery

Chemical modification of polysaccharides (hyaluronic acid,

chitosan, carboxymethylcellulose...)

Peptide-modified hyaluronic acid (HA) hydrogels to control cell behavior

SH

PhotoinitiatorWater, RT

≡SH

HA-p

HS-CH2-CH2-CO-NH- GRGDS

SHHS ≡O

OSH

HSm

O ORO

OR

ONa

O

NH

OR

nCH3OO

ROO

R =

H or

O

i.

ii.

17-21 days

Neurosphere

Neurite

J. Jing et al. Biomacromolecules (2014), 13, 1818-1827D. Tarus et al. ACS Appl. Mater. Interf. (2016), 8, 25051-25059

Hydrogel with tunable mechanical and biochemical properties:Independant control of density of bioactive peptides (GRGDS) crosslinking density

Hydrogel structure => propertiesRGD density effectVertical orientation of neuritesVariation of gel volume

Quantification of neurite density in 3D ➡Higher neurite density for soft gels 400PaOptimum extension for 3% RGD

Two photon microscopy:• Deep penetration of tissue-

like materials (>800 µm)• 3D imaging• Low background noise

A)

B)

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In vitro two-photon microscopy of neural progenitor cells after 17 days of culture. Green: b3-tubuline-FITC

neuronal marker. Red GFAP (astrocytes marker). Hoechst (nuclei marker) 500µm

A)

B)

400 Pa800 Pa

Behavior of neural progenitor cells seeded on HA hydrogels

Interpenetrating hydrogel networks

Time-controllable lipophilic drug release systems fromnanoparticle-hydrogel composites

Interpenetratingnetwork

L. Racine et al. Carbohydr. Polym. (2017), 170, 166–175

L. Racine et al. Macromol. Biosci. (2017), under press

Hydrogel with adjustable properties as patches for drug delivery

Crosslinkingdensity/porosy

NPs/polymerinteractions

Chitosan/poly(ethylene glycol) sponges with excellent mechanical properties and controlled porosity

Thermoresponsive nanogels

Stimuli-responsive nanogels based on polysaccharides for drug delivery and imaging

Nanogel containingmagnetic NPs

pH -responsive and glucose-responsive nanogels