Engineering smart 3D silk fibroin tissue culture scaffolds using reactive inkjet printing

Population aging, increased diseases and unexpected accidents will result in huge demands of tissue/organ transplantation over the next decade. However, the demands are unlikely to be met due to the significant lack of donation and immune mismatching. The breakthrough of tissue engineering and regenerative medicine will offer remarkable success in building three-dimensional tissues suitable for transplantation. 3D porous scaffolds play important roles in tissue engineering not only as structural templates for tissue fabrication but also providing complex signaling cues to cells and facilitating oxygen and therapeutic agent delivery. Therefore, the availability of excellent 3D scaffolds has become one of the aspects that constrains the fast developing of tissue engineering. Production of excellent 3D scaffolds highly relies on i) suitable fabrication technology and ii) excellent candidate biomaterials.

This first grant proposal seeks to harness the emerging additive manufacturing technology (reactive inkjet printing, RIJ) and the unique biomaterial (regenerated silk fibroin, RSF) for the fabrication of smart 3D tissue culture scaffolds. Silk fibroin (a FDA approved biomaterial) is well known for its good biocompatibility, biodegradability, and excellent mechanical properties, therefore, is an ideal candidate as scaffold for tissue engineering/regenerative medicine. Moreover, silk material is widely available worldwide as a cheap feedstock and is mostly used as low-tech/profit material in textile industry. There is plenty of room for exploiting silk as advanced material in high tech/profit industries. One of the applications that have attracted much attention is to develop biomaterials suitable for the fabrication of tissue scaffolds. However, the current RSF scaffolds made through traditional methods (e.g. casting, freeze-drying, electrospinning) have simple structures that are only suitable for lab research or very basic tissue engineering. A suitable manufacturing technology must be found for making advanced 3D scaffolds that provide more effective controls in micro scales. The advantages of RIJ are not only the computer assisted design (CAD) that offers the precise delivery of pico-litres (1e-12 litre) of ink at predetermined locations and that allows the fabrication of complex 3D architectures but also the alternate delivery of different inks (through different print heads) that allows the control of reactions during manufacturing and manipulation of the compositions and the properties of the scaffolds. Therefore, the combination of RSF material and the RIJ technology provide a promising opportunity for fabricating better 3D scaffolds for future regenerative medicine.

There is a global pressure of finding high quality and sustainable materials and using new methods for material processing or fabrication for high valued products. Delivery of this project will have significant input to healthcare technology and provide better tissue culture scaffolds for both user industries (making scaffolds for biomedical research or clinical uses) and end users (clinicians and patients). This project also explores the use of emerging technology (RIJ) for biomaterial fabrication and takes a step forward in transferring lab research to industrial fabrication. Therefore, this project has a number of Economic and Societal Impacts and will facilitate the UK wealth creation, economic prosperity/global competitiveness & knowledge exploitation. The project is also in line with EPSRC priority themes of Healthcare technologies and Manufacturing the future.

Who are the beneficiaries and how they will benefit from this research?

Academics: see previous session on academic beneficiaries.

Skilled People: The research project will train skilled PDRA, PhD and project students and will have direct economic impact via providing skilled people for industry or beneficiary organizations.

Business and User industries: in specific, the biomaterial, biomedical and pharma industries). The results from this project will provide the user industries with better technology for the fabrication of better 3D tissue culture scaffolds with desired properties in a cost-effective manner. It therefore, will facilitate the regenerative medicine in wider clinical applications and will help the user industries maintain their headships in the global healthcare market. The biomedical sector is a key area to support the economic recovery; hence, this project has potential economic benefit. It will also help create job opportunity in user industries.

Public communities: This project will have significant impact to different public communities.
The general public communities: such as patients and clinicians. The eventual beneficiaries of this project are those that will benefit from the growing healthcare techniques. Millions of people are suffering from different diseases that require tissue regeneration or organ transplantation. However, transplantation from other human bodies is limited due to inadequate donation and immune rejection. The outcome of this project will provide better 3D scaffolds for tissue culture which will facilitate regenerative medicine and will benefit millions of patients. Taxpayers will benefit from reduced cost of 3D tissue R&D and eventually lower NHS costs.

Public sectors: such as universities and colleges, health & wellbeing agencies. The findings of this project are excellent teaching materials for universities, colleges and can be used as examples for health & wellbeing agencies or charities.

Animal welfare: The 3D scaffolds have the potential to be used in making 3D tissues as an alternative strategy to animal testing for drug and chemical safety. This will reduce the use of animals in biomedical research which will be beneficial to animal welfare and fits well with the government policy of 3Rs: reducing, replacing and refining the usage of animal in biomedical R&D.