The role of reactive oxygen in wound healing in humans

There is an unmet clinical need for new therapies aimed at improving tissue repair and regeneration, following injury, and to prevent and treat chronic non-healing wounds. We have previously shown that sustained elevated levels of reactive oxygen species (ROS), including hydrogen peroxide, are essential for successful appendage regeneration in tadpoles (Love et al. 2013) and for cell proliferation and tissue formation during embryogenesis (Han et al, 2018a and b; under review in Developmental Cell and Developmental Biology). These findings suggest that sustained, yet controlled, levels of ROS have pro-regenerative activities in frog tadpoles. We and others have also shown that sustained ROS play critical roles in appendage regeneration in other organisms with high regenerative capacity, such as zebrafish, geckos, hydra and planarians. These phenomena have largely been characterised in non-mammalian species, so it remains unknown the relevance of ROS to healing and regeneration in humans. In order to move these findings toward a pre-clinical and clinical phase, in collaboration with the SME, Matoke Holdings Ltd, we propose to evaluate whether Matoke's with the Reactive Oxygen technology platform has pro-healing, pro-regenerative effects in mammalian systems using a variety of novel human ex vivo models and human clinical chronic wound samples.

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.