Developing a technological platform based on the fundamental understanding of peptide self-assembly for the design of novel biomaterials

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

The use of non-covalent self-assembly to construct materials has become a prominent strategy in material science offering practical routes for the construction of increasingly functional biomaterials. A variety of molecular building blocks can be used for this purpose; one such block is de-novo designed peptides. Peptides offer a number of advantages to materials scientists. Peptide synthesis has become a routine procedure making them easily accessible. The library of 20 natural amino acids offers the ability to play with the intrinsic properties of the peptide such as structure, hydrophobicity, charge and functionality allowing the design of materials with a wide range of properties.

The main challenge facing scientists in this field is being able to rationally design these peptides to gain control over the physical properties of the resulting self-assembled materials. This requires not only an in depth knowledge of the self-assembling processes at all length scales, but also a detailed understanding of the specific requirements of each application targeted. A key point that makes the development of an actual technological platform crucial is the variability of the requirements placed on the materials depending on the application targeted. For example, injectable materials need to be developed for cell delivery, while for drug delivery oral cavity sprayable systems could be required. For cell culture and tissue engineering the issue of adaptability of material properties is even more critical as depending on cell type, origin and intended behaviour, cells have very different requirements in term of their environment, (i.e.: material properties and functionality) in which they are placed. Finally, one other key element is the cost of these materials. When used as structural materials such as in hydrogels the quantity of peptide required is significant. In this context the development of a technological platform based on the same family of "simple" and "cheap" to produce peptides that can be used across a number of applications is a significant advantage (see impact summary).

Through this fellowship my group will develop such a technological platform by:
- Developing a fundamental understanding of the self assembly and gelation properties of our materials at all length scales. In particular we will broaden the range of materials and materials properties (e.g.: mechanical, triggering mechanism, injectability) available to be in a position to design and develop new functional and responsive materials
- Develop strong collaborations with academic and industrial end-users. This will allow us to engage end-users with the development process ensuring that the materials we design are relevant and used, and also that we maximise exploration of new potential fields of application
- Develop a comprehensive strategy for the exploitation of the IP generated to maximise the impact of the work at all levels. This will be done in close collaboration with University of Manchester Intellectual Properties (UMIP) and will include the coherent and efficient management of existing and future agreements with industrial and academic partners as well as the development of an efficient process for the identification of novel IPs and their protection and exploitation.

This project will contribute to a number of priorities and Grand Challenges at the centre of EPSRC's remit. It is fully placed within the EPSRC Healthcare Technologies Challenge theme and will directly contribute to the Biomaterials and Tissue Engineering strategic research theme. In addition the work will also contribute towards the EPSRC Regenerative Medicine Grand Challenge and the Chemical sciences and engineering Grand Challenge: Directed Assembly of Extended Structures with Targeted Properties, of which I am a member.

Planned Impact

The fellowship has been designed to maximize the impact of the work to be performed at all levels. For this purpose, as stated in the case for support, the development of a strategy for the management and exploitation of the IPs generated is a core part of the project (Work Package 4). This will be achieved firstly by closely collaborating with academic and industrial end-users and secondly by developing strategic partnerships with companies from producers to distributors and end-users to ensure exploitation of the results. This will be done in close collaboration with UMIP.

Economical impact: Due to the Western economies financial situation the control of health care costs has become a significant issue. The development of a flexible technological platform based on "cheap" to produce peptide will result in significant economical benefit. The multiplicity of end-users will ensure a scale effect resulting in the reduction of costs through development of large scale production methodologies. In addition the validation and certification costs will also be significantly decreased as this will have to be performed only once. This will create new opportunities for end-users generating additional economical activity. The Biomaterial field is also projected to be worth over $90bn by 2020 with a projected annual growth of 6-10% making it a key economical sector for the UK. This fellowship will therefore contribute also to the UK economical activity in the field supporting the country's effort to become a leader in the development of novel Biomaterials.

Industrial impact: We have already started to put in place strategic alliances in the field of peptide production as well as dissemination of our technology to industry. This, in addition to our close collaboration with UMIP and our membership of a number of centres (KCMC, OMIC, MIMIT, Regener8) focussing on knowledge transfer activities, will allow us to access and develop new collaborations with potential end-users that will only be achievable through the length of the fellowship. This will ensure that we generate the maximum transfer of knowledge and impact at an industrial level.

Ethical and societal impact: One of the focuses of our work is to develop fully synthetic scaffolds for cell culture and tissue engineering eliminating the need for animal derived matrix products. We also intend to develop a platform for toxicology testing. Both these activities will actively contribute to the reduction in animal experiments that need to be performed in drug and medical device development. This is a key aim of the national programmes such as the NC3Rs but has been hindered by the lack of suitable 3D culture technologies which provide a tissue-realistic setting for screening.

Publications

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Castillo Diaz LA (2014) Human osteoblasts within soft peptide hydrogels promote mineralisation in vitro. in Journal of tissue engineering

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Elsawy MA (2016) Modification of ß-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation. in Langmuir : the ACS journal of surfaces and colloids

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Markey A (2017) Peptide hydrogel in vitro non-inflammatory potential. in Journal of peptide science : an official publication of the European Peptide Society

 
Description Collaboration with Dr. C. DeMaria University of Pisa 
Organisation University of Pisa
Department Research Centre E. Piaggio
Country Italy 
Sector Academic/University 
PI Contribution Provided hydrogels for printing tests
Collaborator Contribution Printed hydrogels and performed research on fundamental of printing our materials
Impact Publications
Start Year 2013
 
Title Know-how on Method of Making Hydrogels via low pH route 
Description Know-how on Method of Making Hydrogels via low pH route filed with University of Manchester Intellectual Properties company. 
IP Reference  
Protection Protection not required
Year Protection Granted 2013
Licensed Yes
Impact Allowed the set-up of a Start-up company: PeptiGelDesign.Ltd
 
Title Method of Makin and Hydrogel 
Description Method for making a peptide hydrogel using high pH route. 
IP Reference WO/2013/124620 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact Investment from University of Manchester Intellectual Property company.
 
Company Name PeptiGelDesign 
Description Selling of 3D scaffolds for live science sector 
Year Established 2014 
Impact Start trading in 2015
Website http://www.peptigeldesign.com/