Development of immunomodulatory and 3D printable alginate analogues for mitigating foreign body reaction

When a material is implanted in human body (e.g. medical devices, drug delivery systems, scaffolds, sensors), immune cells are the first responders to it. How immune cells react to this material can often dictate how well the material performs its designed functions over its lifetime. One unmet significant challenge in immune system-material interactions is to control foreign body reaction (FBR) following implantation of a biomaterial. FBR is composed of macrophages and foreign body giant cells adhered to implanted biomaterials and is the end-stage response of the inflammatory and wound healing responses. FBR can result in the recruitment of fibroblasts that actively deposit matrix to isolate and wall off a foreign material, which is called fibrous encapsulation. FBR and fibrous encapsulation can significantly compromise the functionalities of implanted biomaterials or even cause the failure of them. There are currently no clinically approved biomaterials that can mitigate or evade FBR.

The project will explore how material chemical and architectural properties can be utilised to mitigate FBR to implanted biomaterials, and elucidate the underlying cellular and molecular mechanisms. Novel biomaterials that have both 3D printability and immune-instructive properties will be developed, which will significantly expand the architectural range of these materials. The interplay between chemistry and architecture in FBR will be investigated, which will generate new knowledge on biomaterial-immune cell interactions.

Immune response is a crosscutting theme in the development of new therapies and devices that include biomaterials as an integral part. The importance of material-related immune responses has been increasingly recognised, which is evident in recent publications in biomaterials, tissue engineering and regenerative medicine. The outcomes of this project can potentially be plugged into multiple applications including drug delivery, tissue engineering, regenerative medicine, and medical devices.

Pharmaceutical technologies underpin healthcare product development. Medicinal products are becoming increasingly complex, and while the next generation of research scientists in the life- and pharmaceutical sciences will require high competency in at least one scientific discipline, they will also need to be trained differently than the current generation. Future research leaders need to be equipped with the skills required to lead innovation and change, and to work in, and connect concepts across diverse scientific disciplines and environments. This CDT will train PhD scientists in cross-disciplinary areas central to the pharmaceutical, healthcare and life sciences sectors, whilst generating impactful research in these fields. The CDT outputs will benefit the pharmaceutical and healthcare sectors and will underpin EPSRC call priorities in the development of low molecular weight molecules and biologics into high value products.

Benefits of cohort research training: The CDT's most direct beneficiaries will be the graduates themselves. They will develop cross-disciplinary scientific knowledge and expertise, and receive comprehensive soft skills training. This will render them highly employable in R&D in the pharmaceutical, healthcare and wider life-sciences sectors, as is evidenced by the employment record in R&D intensive jobs of graduates from our predecessor CDTs. Our students will graduate into a supportive network of alumni, academic, and industrial scientists, aiding them to advance their professional careers.

Benefits to industry: The pharmaceutical sector is a key part of the UK economy, and for its future success and international competitiveness a skilled workforce is needed. In particular, it urgently needs scientists trained to develop medicines from emerging classes of advanced active molecules, which have formulation requirements that are very different from current drugs. The CDT will make a considerable impact by delivering a highly educated and skilled cohort of PhD graduates. Our industrial partners include big pharma, SMEs, CROs, CMOs, CMDOs and start-up incubators, ensuring that CDT training is informed by, and our students exposed to research drivers in, a wide cross-section of industry. Research projects in the CDT will be designed through a collaborative industry-academia innovation process, bringing direct benefits to the companies involved, and will help to accelerate adoption of new science and approaches in the medicines development. Benefit to industry will also be though potential generation of IP-protected inventions in e.g. formulation materials and/or excipients with specific functionalities, new classes of drug carriers/formulations or new in vitro disease models. Both universities have proven track records in IP generation and exploitation. Given the value added by the pharma industry to the UK economy ('development and manufacture of pharmaceuticals', contributes £15.7bn in GVA to the UK economy, and supports ~312,000 jobs), the economic impacts of high-level PhD training in this area are manifest.

Benefits to society: The CDT's research into the development of new medical products will, in the longer term, deliver potent new therapies for patients globally. In particular, the ability to translate new active molecules into medicines will realise their potential to transform patient treatments for a wide spectrum of diseases including those that are increasing in prevalence in our ageing population, such as cardiovascular (e.g. hypertension), oncology (e.g. blood cancers), and central nervous system (e.g. Alzheimer's) disorders. These new medicines will also have major economic benefits to the UK. The CDT will furthermore proactively undertake public engagement activities, and will also work with patient groups both to expose the public to our work and to foster excitement in those studying science at school and inspire the next generation of research scientists.