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

Developing a technological platform for

the design of novel 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)

Exploits self-assembling properties β-sheet forming peptides

The Technology

β-sheet forming peptide pH, time, temp.,

• r enzyme

C > CGC

F F F F E E K K A A A A E E K K F F F F E E R R

10 100

C / mg ml-1

10 100 1000 10000

G' / Pa

FEFEFKFK FEFKFEFK VEVEVKVK VEVKVEVK LELELKLK

Molecular architecture Structure / Morphology Physical properties

correlations

 Functional hydrogels  Responsive hydrogels

LCST

+ RGD

Exploits self-assembling properties β-sheet forming peptides

C > CGC β-sheet forming peptide functionalised peptide biologically active peptide sequence, drug, ect...

Key feature:

The Technology

Achievements to date

Sprayable muco-adhesive hydrogels for sustained drug delivery (PCT Patent with RB)

20 40 60 80 100 10 20 30 40 50 60 FEFEFKFK [20] + Benzocaine [20] pH 2.4 FEFEFKFK [30] + Benzocaine [20] pH 2.3 FEFEFKFK [20] + Benzocaine [20] pH 6.8 FEFEFKFK [30] + Benzocaine [20] pH 6.7 Cumulative retention / % Time / min

LCST Responsive hydrogels for controlled drug delivery (PCT Patent with Solvay) Hydrogels for cardiac patch (PCT Patent with PERA)

INNOVATE

Injectable hydrogels for cell/drug delivery (Parma & MHH) Hydrogels for stem cell culture (PCT Patent with Dr. C. Merry)

MATERIAL INNOVATION

Fully integrated engineering approach to the design of materials in close collaboration with end-users

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  My time Total FEC value of grant: £2.3M 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

Biocatalysis

(Dr. A. Miller & Prof N. Scrutton)

Cartilage repair

(Prof B. Derby & MD. T Woolford)

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 Stem cell culture

(Dr. C. Merry)

Chondrocytic Differentiation

(Solvay)

Muco- adhesive Hydrogels

(RB)

Intervertebral disk repair

(Dr. J Gough)

Nerve repair

(Prof. G Terenghi & MD D. Reid)

Cardiac patch (PERA) Biosensors

(Dr. A.F. Miller & PERA)

Spinal cord drug delivery

(Dr. J Taylor & PERA)

Biocatalysis

(Dr. A. Miller & Prof N. Scrutton)

Cartilage repair

(Prof B. Derby & MD. T Woolford)

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 Stem cell culture

(Dr. C. Merry)

Chondrocytic Differentiation

(Solvay)

Muco- adhesive Hydrogels

(RB)

Intervertebral disk repair

(Dr. J Gough)

Nerve repair

(Prof. G Terenghi & MD D. Reid)

Cardiac patch (PERA) Biosensors

(Dr. A.F. Miller & PERA)

Spinal cord drug delivery

(Dr. J Taylor & PERA)

WP4: Exploitation strategy

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