the design of no vel biomaterials Alberto Saiani School of - PowerPoint PPT Presentation

Developing a technological platform for the design of no vel biomaterials Alberto Saiani School of Materials The University of Manchester www.polymersandpeptides.co.uk

The Man • 1994-97 European Ph.D., Université Louis Pasteur, Strasbourg, France Thermoreversible Gelation of Syndiotactic Poly[Methyl Methacrylate] • 1997-98 Post Doctoral Stay, Osaka University, Japan (JSPS Grant) Structure of Isotactic Polybutene-1 : Form II • 1998-00 Research Associate, Imperial College, London, UK Phase Behaviour - Morphology of High Hard Block Content Polyurethanes Phase Separation in Rubber Toughened PMMA • 2000-02 Lecturer Université Blaise Pascal, Clermont-Ferrand, France • 2002- Lecturer/Reader Molecular Material (UMIST/UoM) Moved to the biomaterial/biomedical field in 2006

EPSRC Fellowships Three types of fellowships: - Post-Doctoral - Early Career - Established Career Specific fields are available for each type - Need to check EPSRC website (Healthcare Technologies) - Can’t understand when these are changed - If you apply inform EPSRC so you can be told until when the call is open ⇒ I went for early career!

Fellowships writing Writing was a long process: Took me ~ 1 year from thinking about it to submitting Managed to get a copies of successful applications Need motivation: Science and scale of multidisciplinary project About to loose 3 PDRA on 3 separate grants Became unable to follow all the opportunities Feedback was crucial: - from expert in the field (science) - from non-expert in the field (impact section) - from UMIP (management and IPs) - EPSRC (eligibility and technical)

The Technology Exploits self-assembling properties β -sheet forming peptides pH, time, temp., C > CGC or enzyme β -sheet forming peptide Molecular architecture Structure / Morphology Physical properties 10000 G' / Pa F F F F F F F F 1000 E E K K E E R R LELELKLK FEFKFEFK VEVEVKVK 100 A A A A VEVKVEVK FEFEFKFK E E K K C / mg ml -1 10 10 100 correlations

The Technology Exploits self-assembling properties β -sheet forming peptides C > CGC β -sheet forming peptide functionalised peptide biologically active peptide sequence, drug, ect... Key feature: + RGD  Functional hydrogels  Responsive hydrogels LCST

Achievements to date Fully integrated engineering approach to the design of materials in close collaboration with end-users Hydrogels for cardiac patch (PCT Patent with PERA) LCST Responsive hydrogels for controlled drug delivery Injectable hydrogels for (PCT Patent with Solvay) MATERIAL cell/drug delivery INNOVATE (Parma & MHH) INNOVATION 100 80 Cumulative retention / % 60 FEFEFKFK [20] + Benzocaine [20] pH 2.4 FEFEFKFK [30] + Benzocaine [20] pH 2.3 40 FEFEFKFK [20] + Benzocaine [20] pH 6.8 FEFEFKFK [30] + Benzocaine [20] pH 6.7 20 0 0 10 20 30 40 50 60 Time / min Sprayable muco-adhesive hydrogels Hydrogels for stem cell culture for sustained drug delivery (PCT Patent with Dr. C. Merry) (PCT Patent with RB)

Key Challenges Design of tailored materials  fundamental understanding of self-assembly process  development of design rules Translation to the biological field  end-users requirements  environment in which material has to operate Transfer to end-user  develop viable protocols  support end-user early stage usage

Why a fellowship? Ambitious project which requires a step change in the work performed to achieve full potential of technology proposed  Significant resources which go beyond a simple grant  Critical mass of skilled researchers across fields:  chemistry / physical chemistry  formulation / material engineering  cell culture / tissue engineering  animal work / bio-toxicity  Significant travel to ensure close collaboration with end- users  My time

Why a fellowship? Ambitious project which requires a step change in the work performed to achieve full potential of technology proposed  Significant resources which go beyond a simple grant  Critical mass of skilled researchers across fields:  chemistry / physical chemistry  formulation / material engineering  cell culture / tissue engineering  animal work / bio-toxicity  Significant travel to ensure close collaboration with end- users Total FEC value of grant: £2.3M  My time 14 years of PDRA

The Fellowship WP1: Fundamental understanding molecular and formulation design paradigms

The Fellowship WP1: Fundamental understanding molecular and formulation design paradigms WP2: Material engineering Cell-culture, Toxicology, Drug delivery & Bioreactors

The Fellowship WP1: Fundamental understanding molecular and formulation design paradigms WP2: Material engineering Cell-culture, Toxicology, Drug delivery & Bioreactors WP3: Translation to the biological field Delivery of iPS cells (MHH) Culture of cancer initiating cells (Parma) Antibacterial hydrogels (Tübingen) In-vivo peptide fate

The Fellowship Cardiac patch (PERA) Stem cell culture Chondrocytic (Dr. C. Merry) Differentiation WP1: (Solvay) Fundamental understanding Biosensors molecular and formulation (Dr. A.F. Miller design paradigms Intervertebral & PERA) disk repair (Dr. J Gough) Muco- WP2: Material engineering adhesive Cell-culture, Toxicology, Hydrogels Spinal Drug delivery & Bioreactors (RB) cord drug delivery Biocatalysis WP3: Translation to the biological field (Dr. J Taylor (Dr. A. Miller & Delivery of iPS cells (MHH) & PERA) Prof N. Scrutton) Culture of cancer initiating cells (Parma) Antibacterial hydrogels (Tübingen) Nerve repair Cartilage repair (Prof. G Terenghi In-vivo peptide fate (Prof B. Derby & MD D. Reid) & MD. T Woolford)

The Fellowship Cardiac patch (PERA) Stem cell culture Chondrocytic (Dr. C. Merry) Differentiation WP1: (Solvay) Fundamental understanding Biosensors molecular and formulation (Dr. A.F. Miller design paradigms Intervertebral & PERA) disk repair (Dr. J Gough) Muco- WP2: Material engineering adhesive WP4: Cell-culture, Toxicology, Hydrogels Exploitation Spinal Drug delivery & Bioreactors (RB) strategy cord drug delivery Biocatalysis WP3: Translation to the biological field (Dr. J Taylor (Dr. A. Miller & Delivery of iPS cells (MHH) & PERA) Prof N. Scrutton) Culture of cancer initiating cells (Parma) Antibacterial hydrogels (Tübingen) Nerve repair Cartilage repair (Prof. G Terenghi In-vivo peptide fate (Prof B. Derby & MD D. Reid) & MD. T Woolford)

EPSRC Fellowships Key points: - Fellowship funds a person and a career: 3 of the 7 criteria are about the applicant: ability to deliver, research vision, leadership potential - I changed the way I write from science to impact and potential: strong focus on interactions with end-user Referee scores: - 4: contradicted itself - 5: question interactions with some collaborators - 6: last killer sentence: I am too experienced for early stage  All three referees were unanimous in praising ME

EPSRC Fellowships Materials Panel: - Ranked against all the other materials fellowship (4/15) Interview: - Ranked against all the other early career fellowships (2/11) - No bio-person on the panel - No healthcare technologist on the panel Fellowship impact: - Time to do science: no admin and limited teaching - No financial pressure for a couple of years - Ability to fulfil potential on the work: spin-out

EPSRC Fellowships Thank you / Questions