Tailored made degradable synthetic polymers for 3D (bio)printing - PowerPoint PPT Presentation

“ Tailored made degradable synthetic polymers for 3D (bio)printing ” “Maastricht, January 26 th 2016” Prof. Christian GRANDFILS www.ceib.ulg.ac.be C.Grandfils@ulg.ac.be 1

Specific expertises 1. Polymer synthesis www.ceib.ulg.ac.be biodegradable polyesters ; functionalized poly(methyl)acrylate 2. Polymer processing • Hydrogels • Film • Dispersed materials : micelles, nano- microparticles • drug immobilisation 3. Analytical • Solubility, Mw determination • Stability, releaase kinetics study • Particle characterisation 4. In vitro toxicity -Hemocompatibiliy - Animal cell tox 2

Particle Drug Delivery Drug formulation GENERAL In vitro testing ORGANISATION OF THE RESEARCH Polymer synthesis Cell therapy – Tissue engineering In vivo testing VALORISATION : Patents – Close collaboration with industries – Analytical services 3

Biodegradable polyesters  Macromolecular engineering with controlled polymerisation mechanism of cyclic monomers such as lactides, lactones. Novel architectures: block graft, random star-branched copolymers  PolymerTECH : more than 300 different polymer samples available  Material type : thermoplastics, hydrogels, amphiphilic gels  Batch size : from g to 100 g ; in the near future : Kg scale facilities with reactive extrusion polymerisation Synthetic polyelectrolytes  Living radical polymerisation of acrylic monomers  Stimuli-responsive polymers.  Functionalized polymers with reactive groups for synthesis of bioconjugates and fluorescent labelling of biomaterials.  Strongly adhering polymers  Bulk polymerisation and purification in aqueous medium 4

Amphiphilic Biodegradable and biocompatible Hydrogels Increase the softness of the material by increasing it’s hydrophilicity L - H - L L - H - L hydrophobe hydrophile 250 15 min 24 h 1 semaine 200 Prise de masse [%] 150 100 50 H 0 0 10 20 30 40 50 60 70 Proportion molaire de PEO [%] 5

CEIB PolymerTech About 300 purified polyesters in stock differing in : • Mw • composition • tacticity • sequence : di- tri- block • amphilicity 6

Examples of polymer series PEO-P(D,L)LA PEO-P(L,L)LA code Mw code Mw CK023 350-3000 CK013 350-3000 CK024 350-7500 CK014 350-7500 CK025 350-15000 CK036-6 350-12500 CK028 350-43000 CK016 350-55000 CK029 350-140000 CK194 350-140000 P(D,L)LA-PEO-P(D,L)LA P(L,L)LA-PEO-P(L,L)LA code Mw code Mw NM008 3400-9000-3400 NM002 3800-9000-3800 7

PolyLIFE – First spin-off F. Lombart SCALE-UP Applications of the extrusion : • Continuous polyesters synthesis according to a reactive extrusion process • Polymer processing • Polymer – drug blends

Scaling-up of polymer synthesis – Spin-off : PolyLife GMP – platform for polymer synthesis – material processing – drug encapsulation - Scale : minimal batch size : 15 g up to Kg - GMP equipment Solid / liquid feeding – control atmosphere - - Mw of PLA : up to 250,000 Da : residence time : from 1 to 25 min. 9

Polymer deposition by Aerosol Inject Printing technology (AJP) (in collaboration with Sirris) Actual resolution of the polymer deposition : 40 µm

Porosity of 3D scaffolds analysed by RX µ-CT Pore size distribution of 3 scaffolds 51 6 51 5 51/52 Pourcentage [%] 52 4 51/52 3 2 1 52 0 0.000 0.200 0.400 0.600 0.800 1.000 1.200 Taille des pores [mm] 51 51/52 52 11

Degradable textiles and stem cells . Multifilament Monofilament Multifilament Monofilament Osteoblast cells Stem cells Cell appearance after a 24 hours incubation with 3D textile (Confocal microscopy after fibers morphology analysis (LIVE/DEAD Kit´s labeling) Ref : Ortiz et al, J. Biomedical Mat. Research (part B), 2016.

Biocompatible biodegradable composite gel / textile for tissue engineering

New Synthetic Antidote of Heparin – PCT Patent PCT/EP2014/067081 Ch Grandfils, L. Flebus, Ch. Sevrin Extracorporeal blood circulation

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