Internship surgery

’73 - ’83 ’84 ’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ‘03 ‘05 ‘07 ‘09 ‘11

Children’s Hospital of Eastern Ontario experimental spinal cord injury (SCI)

Neurobiology Res Ctr QC Res Ctr in Science & Macromol Eng biomaterials concept for neuroregeneration

Keele University polymer drug delivery

Prague Institute of Macromol Chemistry bioactive hydrogel formulation & dev.

Quebec Biomaterial Institute adjunct faculty invention of Neurogel as novel approach to SCI

Organogel Canada Ltd

Organogel Canada Ltd

CERMAV-CNRS GIN-Inserm program directorbioretina glycosylated hydrogels neural stem cell recruitment

France Canada uk Czech Rep. Canada France

EMPLOYMENT

Areas represent relative energy expenditure over timeRESUME/ROADMAP INFOGRAPHIC Stéphane Woerly MD PhD

Medical Research Council Fellowship

ACADEMICS

Pie slices represents approx. percentage time investment

graduation

MD training neurochemistry

graduation

Polymeric biomaterialsNeurodegenerationNeuroregeneration

physical-chemistrypolymerization processHydrogel chemistry

CSOexperimental surgery preclinical proof-of-concept on established SCI models

creation of Organogel Canada LtdQuebec Metro High Tech Parkfundraising/IP development

CMOclinical master file new treatment option to SCIendogenous regenerative technology

Neuro polymer professional

Neurogel development

(biomaterials ‘90)

Macroporous pHPMA Hydrogel

© Copyrights Woerly

A proprietary innovative technology platform with applications in Tissue Neuro-Engineering and RegenMed

A proprietary innovative technology platform with applications in Tissue Neuro-Engineering and RegenMed

Tissue-building properties

of pHPMA hydrogel

New AstrocyticTissue Matrix

Axonal Growth

Angiogenesis

Signaling moleculecirculation

Stem cell recruitment

EM Structure imaging of HPMA EM Structure imaging of HPMA hydrogel hydrogel macro/mesoporesEM Structure imaging of HPMA EM Structure imaging of HPMA hydrogel hydrogel macro/mesopores

Cross-linked poly[N-(2-hydroxypropyl) methacrylamide] hydrogel showsa macromolecular architecture with a colloidal-type structure

3D section plot

Volume viewer

EM Structure imaging of HPMA EM Structure imaging of HPMA hydrogel hydrogel microporesEM Structure imaging of HPMA EM Structure imaging of HPMA hydrogel hydrogel micropores

Micropores on the surface of microgels that increase the surface area of the bulk of the hydrogel network

in vivo confocal imaging of in vivo confocal imaging of hydrogelhydrogelpolymer/CNS tissue interface

Polymer-tissue interfacePolymer-tissue interface

CNS tissueCNS tissue

in vivo confocal imaging in vivo confocal imaging (I)(I)immuno-labeling of stem cell migration within the hydrogel intracerebral implantation (4 month post-grafting)

in vivo confocal imaging in vivo confocal imaging (I)(I)immuno-labeling of stem cell migration within the hydrogel intracerebral implantation (4 month post-grafting)

in vivo confocal imaging (II)in vivo confocal imaging (II)immuno-labeling of stem cell migration within the hydrogel intracerebral implantation (4 month post-grafting)

in vivo confocal imaging (III)in vivo confocal imaging (III)immuno-labeling of stem cell migration within the hydrogel implanted in the spinal cord (17 month after trauma and post-grafting)

neurofilament/MBP (red) Nestin (green)/MBP(red)

The arrow and the insert show a NF+ neuronal cell body

in vivo confocal imaging in vivo confocal imaging nerve fibres growth within the hydrogel pore network

in vivo confocal imaging in vivo confocal imaging nerve fibres growth within the hydrogel pore network

3D hydrogel volume reconstruction 3D hydrogel volume reconstruction cell distribution (red dots) within the pore structure

in vivo confocal imaging in vivo confocal imaging angiogenesisin vivo confocal imaging in vivo confocal imaging angiogenesis

Growing blood vessels within the polymer network

in vitro SEM imaging in vitro SEM imaging HPMA hydrogel including human neuroblastoma cells

in vitro SEM imaging in vitro SEM imaging HPMA hydrogel including human neuroblastoma cells

Neurite extending within the polymer

network

Neurite extending within the polymer

network

Cell aggregates Cell aggregates

in vitro nestin-hoescht imaging in vitro nestin-hoescht imaging hydrogel including primate neural precursor cells *

* source: Stem cell and Brain Research Institut of Lyon

Polymer networkPolymer network

Key features of NeurogelKey features of Neurogel

• Elastic modulus matches that of CNS

• Tensile strength across the area of transplantation

• Porosity allows cells, growth factors and axonal elongation to fill the lesion site

• Does not breakdown—allows for enough time for regeneration

• Promotes the exclusion of scar tissue and Wallerian degeneration in the transected spinal cord

• flexible platform for the optimization of scaffold functionality

• Good surgical procedure feasibility

Current developmental statusCurrent developmental status

• Laboratory prototypes• Product Requirement Specifications• Verification & validation• Preclinical Proof-of-concept (SCI)• Toxicology/biocompatibility testing• Sterility assurance• Packaging & stability issues

Neurotechnology / proof-of-principle

HPMA hydrogel graft acrossa lesion of the spinal cord

Gross anatomy of theimplantation site 15 months post-surgery

Introduction of a sialyl derivative group (immunolabeled in green) to create specific biological properties

Functionalization of HPMA hydrogel