Stimulatory nanofibre conduits for peripheral nerve regeneration
Lead Research Organisation:
University of Manchester
Department Name: School of Health Sciences
Abstract
Promoting axon regeneration following trauma is a major surgical challenge, exploiting the mechanisms that regulate axon growth/guidance is essential to achieve this goal. Biomaterials are being developed to manipulate cellular interactions with their environment [1]. The majority of engineered systems present signals (mechanics, topography, adhesion) in a spatially uniform manner. Biochemical patterns are more indicative of natural extra cellular matrix (ECM) signalling that occurs through gradients and spatial localisation of biomolecules, and their use in combination with topographical features is a powerful tool for guiding axons to their synaptic targets.
This project combines a new nanofibre spraying technique, solution blow spinning (SBS) [2], with a mask-less digital photolithography technique to photo-click/tether growth factors into concentration gradients and defined patterns on chitosan/silk-based nanofibres. Chitosan, silk, hyaluronic acid (HA), and poly(ethylene glycol) amongst others can be functionalized with groups that allow photo-clicking (norbornene/thiol groups for example), and their formulations sprayed into fibres. SBS allows multi-layer hierarchical composites to be produced that can match the mechanical properties of native tissue and be more resilient to surgical handling/suturing. Masked lithography has been used on nanofibres but is currently restricted to 2D nanofibre membranes [3]. The combination will allow a new generation of stimulatory hierarchical NGCs to be produced with tethered growth factors patterned in the interior of the 3D conduit, as a tool to optimise axonal growth.
This project combines a new nanofibre spraying technique, solution blow spinning (SBS) [2], with a mask-less digital photolithography technique to photo-click/tether growth factors into concentration gradients and defined patterns on chitosan/silk-based nanofibres. Chitosan, silk, hyaluronic acid (HA), and poly(ethylene glycol) amongst others can be functionalized with groups that allow photo-clicking (norbornene/thiol groups for example), and their formulations sprayed into fibres. SBS allows multi-layer hierarchical composites to be produced that can match the mechanical properties of native tissue and be more resilient to surgical handling/suturing. Masked lithography has been used on nanofibres but is currently restricted to 2D nanofibre membranes [3]. The combination will allow a new generation of stimulatory hierarchical NGCs to be produced with tethered growth factors patterned in the interior of the 3D conduit, as a tool to optimise axonal growth.
Planned Impact
Regenerative medicine aims to develop biomaterial and cell-based therapies that restore function to damaged tissues and organs. It is a priority of the University and the nation, and a central focus of the EPSRC challenge theme "Healthcare Technologies". It is also an MRC strategic priority, "Repair and replacement: to translate burgeoning knowledge in regenerative medicine into new treatment strategies". It is in recognition of the challenges associated with clinical translation of regenerative medicine that EPSRC, MRC, BBSRC and TSB jointly funded the £25m UK Regenerative Medicine Platform - UoM is a partner on all three funded national hubs: 'Engineering and exploiting the stem cell niche', 'Acellular technologies, 'Safety and efficacy'. Our Centre for Doctoral Training in Regenerative Medicine, and hub partnerships, will have major impact by delivering a cohort of highly training scientists and clinicians who can take regenerative medicine to the next level of therapeutic efficacy, and engage with these national hubs. This capability will enable the UK to retain its position as a world-leader in regenerative medicine.
Specific impacts include:
(i) Biomedical scientists, the UK regenerative medicine community and international colleagues
Major impact will be achieved by training our students in the scientific methods required to: understand how the microenvironment (niche) directs cells to remodel tissues; design (nano)materials that interact at a mechanical and biochemical level with cells and orient their behaviour; understand how inflammatory processes affect regeneration; translate this knowledge to patients.
Our students will have the outstanding opportunity of benefiting directly from, and contributing directly to all the national UK Regenerative Medicine Platform hubs.
Added value will be achieved through research collaborations and data/reagent sharing across the University of Manchester and the Manchester Academic Health Science Centre, nationally through the hubs, and internationally through our six world-leading doctoral centre partners.
The Centre's strong links with MIMIT (Manchester: Integrating Medicine and Innovative Technology; linked to CIMIT, Boston USA), which develops clinical solutions for tissue repair and related unmet clinical needs, and with the Manchester Collaborative Centre for inflammation Research, enable our students to develop new regenerative strategies that encompass inflammatory control.
(ii) Biopharma
The ability to direct the effective repair or regeneration of tissues is highly sought after by cell therapy/regenerative medicine/tissue engineering companies wishing to translate these discoveries to new therapeutic products, and to Biopharma to inform the design and delivery of niche-based biologics and MSC-based anti-inflammatory therapies. We have more than 30 industrial partners, attesting to the strength of our Centre plan.
Our students will be advised by the University of Manchester Intellectual Property (UMIP) in all aspects of commercialisation, e.g. selling/licensing of reagents, provision of research expertise, in-house assays/techniques, co-development of technologies or licensing of IP.
(iii) General Public
The Centre will be a powerful platform for the Centre students to inform the public about our regenerative medicine activities and therapeutic advances.
The students will write review articles for popular press and student science magazines; develop skills in communications and public engagement; participate in Manchester Science Week and internet fora; develop outreach materials to inform local, national and international audiences, and meet patient groups.
Specific impacts include:
(i) Biomedical scientists, the UK regenerative medicine community and international colleagues
Major impact will be achieved by training our students in the scientific methods required to: understand how the microenvironment (niche) directs cells to remodel tissues; design (nano)materials that interact at a mechanical and biochemical level with cells and orient their behaviour; understand how inflammatory processes affect regeneration; translate this knowledge to patients.
Our students will have the outstanding opportunity of benefiting directly from, and contributing directly to all the national UK Regenerative Medicine Platform hubs.
Added value will be achieved through research collaborations and data/reagent sharing across the University of Manchester and the Manchester Academic Health Science Centre, nationally through the hubs, and internationally through our six world-leading doctoral centre partners.
The Centre's strong links with MIMIT (Manchester: Integrating Medicine and Innovative Technology; linked to CIMIT, Boston USA), which develops clinical solutions for tissue repair and related unmet clinical needs, and with the Manchester Collaborative Centre for inflammation Research, enable our students to develop new regenerative strategies that encompass inflammatory control.
(ii) Biopharma
The ability to direct the effective repair or regeneration of tissues is highly sought after by cell therapy/regenerative medicine/tissue engineering companies wishing to translate these discoveries to new therapeutic products, and to Biopharma to inform the design and delivery of niche-based biologics and MSC-based anti-inflammatory therapies. We have more than 30 industrial partners, attesting to the strength of our Centre plan.
Our students will be advised by the University of Manchester Intellectual Property (UMIP) in all aspects of commercialisation, e.g. selling/licensing of reagents, provision of research expertise, in-house assays/techniques, co-development of technologies or licensing of IP.
(iii) General Public
The Centre will be a powerful platform for the Centre students to inform the public about our regenerative medicine activities and therapeutic advances.
The students will write review articles for popular press and student science magazines; develop skills in communications and public engagement; participate in Manchester Science Week and internet fora; develop outreach materials to inform local, national and international audiences, and meet patient groups.
Organisations
People |
ORCID iD |
| Nicola Tirelli (Primary Supervisor) |
| Description | Neuronal axon regeneration after significant peripheral nerve injury relies on existing structures and chemical cues. This project aims to develop a material with structural and chemical cues that will stimulate neurons to regenerate faster, limiting the extent of permanent damage after injury. Funding for this award has insofar resulted in the development of a system to spatially pattern a biomaterial with stimulatory cues. |
| Exploitation Route | Successful development of the chemical patterning system will provide an additional tool in the arsenal for manufacturing stimulatory nerve conduits for severe peripheral nerve injury intervention. |
| Sectors | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | British Science Week 2019 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Schoolchildren and parents/guardians are brought in contact with basic concepts of tissue engineering and regenerative medicine, by means of playing interactive and problem-solving games developed by the public engagement team of the CDT for Regenerative medicine of the University of Manchester. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Marvellous Engineering at Manchester |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | ~20 year 12 students are brought in touch with aspects of biomaterials, through a problem-solving exercise of selecting the best biomaterial for a specific application. The application of biomaterials requires the collaboration of a range of different science and engineering disciplines. This session introduces a tangent of materials engineering where the applications range from the everyday (plasters, contact lenses) to the extreme (conduits for nerve repair, tissue models for personalised drug testing). |
| Year(s) Of Engagement Activity | 2019 |
| Description | Science spectacular event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Schoolchildren and parents/guardians are brought in contact with basic concepts of tissue engineering and regenerative medicine, by means of playing interactive and problem-solving games developed by the public engagement team of the CDT for Regenerative medicine of the University of Manchester. |
| Year(s) Of Engagement Activity | 2018 |