Regenerative biomaterial patches for failing hearts

Regenerative medicine has been established as a powerful approach to repair and restore tissue function and has facilitated the development of a new era of medical procedures and healthcare technologies including the delivery of stem cells. However, many of these technologies have failed to reach the clinic due to poor methods of cell delivery which lead to rapid cell death or poor engraftment with the target tissues intended for repair.

To improve clinical outcomes, biomaterials have been developed with the aim to control cell delivery in sustained and localised manner. However, biomaterials currently under investigation are not able to adhere to target tissues and rely on sutures to hold them in place which induces further tissue damage and inflammation. Furthermore, a mechanical demanding environment such as beating heart requires the biomaterial to be robust and able to conform to the dynamic nature of the tissue. For example, myocardial infarction can lead to the death of 1 billion cardiomyoctes and cell-delivery to infarcted hearts is an emerging therapy to heal the diseased cardiac tissue. However, the efficacy of these treatments has been limited due to the lack of advanced cell-delivery methods.

The overall goal of this research is to improve clinical outcomes associated with regenerative cell-based therapies by using advanced biomaterials as cell-delivery vehicles. This project aims to provide advanced biomaterials for regenerative medicine by delivering cardiac cells to diseased tissue via adhesive hydrogel patches. Such an approach would provide opportunities and have significant impact in fields such as biomaterials, regenerative medicine, drug delivery, medical devices and tissue engineering.

The specific biomaterials that will be developed to deliver cells are hydrogels which are high-water content swollen gels. Hydrogels are a highly desirable class of materials to encapsulate cells as they can be synthesised to mimic natural tissues which increases the biocompatibility of these systems. Furthermore, the hydrogels can provide information to the encapsulated cells to encourage tissue-specific cell differentiation prior to delivery to the target diseased tissue.

The hydrogels developed in this research are highly stretchable, so they can be deployed in physical demanding environments, and tissue adhesive which allows the encapsulated cells to closely interface with the tissue surface and be delivered more efficiently.

The outcomes of this research would open up new opportunities for regenerative medicine as these hydrogels could significantly increase the efficiency of cell-based therapies, improve our treatment methods and understanding of diseased tissues and introduce innovative cell-laden biomaterials to the clinic as regenerative medical devices.

Societal Impact: Cardiovascular diseases are the leading causes of death worldwide and myocardial infarction (MI) is one of leading contributors to this. In the United States, one person suffers MI every 34 seconds. According to the British Heart Foundation someone in the UK dies from coronary heart disease every 8 minutes and every 3 minutes a person visits the hospital after MI. This comes at a huge cost to our healthcare services where we spend £9 billion annually on heart and circulatory diseases.
Around 1 billion cardiomyocytes die following MI and to functionally repair the heart tissue, these contractile cells need to be replaced. The technology outlined in this project could significantly impact the way we treat MI by incorporating regenerative medicine into cardiac surgery to regenerate heart tissues following MI.

Innovation and wealth-creation for the UK: The core project themes of Advanced Materials and Regenerative Medicine match National Priority areas for UK research and innovation. The foundational academic research of this project will have a significant and wide impact on the growing number of start-ups, SMEs and corporations in the UK and abroad that use biomaterials as part of their research and revenue stream.
Development of adhesive hydrogels for cell therapy will have wide-ranging impact beyond the fellowship objectives (i) facilitate development of hydrogel coatings for medical implants; (ii) inform new medical devices development, including stents, meshes and support structures that may be derived from hydrogels (iii) enable new product development for pharmaceutical applications, e.g. as biocompatible delivery systems for active components. My development of adhesive hydrogels for cell therapy demonstrates my capacity to establish and maintain world-leading research activity and fellowship training will enable me to drive innovation in the area and develop business opportunities for UK industry in biomaterials.