Design Optimisation of Tissue Scaffolds Using Patient-specific and In Vivo Criteria

Background:
As a result of increasing life expectancy diseases in bone and various types of soft tissue have become a major health concern. For example, in the UK, musculoskeletal conditions are a major area of NHS expenditure, consuming £4.76 billion in 2009-2010 alone. Currently cancer affects one in three of us during our lifetime and, in 2010, the costs of cancer diagnosis and treatment across the UK was estimated at £9.4 billion. The treatment process can require significant amounts of tissue to be removed or destroyed, with the resulting damage requiring a supply of appropriate viable tissues from the patient or from donors which may be of limited availability. Tissue engineering, as a fast emerging interdisciplinary area, offers enormous potential to solve such a critical problem in public health and socio-economy. Not only does the scaffold create a structural matrix to generate the required spatial tissue anatomy, but also provides a vehicle for the nutrient intake and waste product removal from/to the surrounding environment necessary for cell proliferation and tissue growth. However, there remain critical challenges, including a 'lack of quantitative design optimisation approach for scaffold architecture' and 'how to incorporate in vivo environment and patient-specific factors in scaffold selection', which to some extent prevent tissue engineering from being translated to a clinically-adoptable technology.

Programme and Methodology
This First Grant proposes to address the challenges identified above and, more importantly, to make critical steps forward in bridging the gap between the advances in in vitro tissue engineering and its ultimate goal of 'in vivo tissue regeneration' by giving it an additional dimension of vitality, i.e. design optimisation of scaffolds subject to tissue-specificity and patient-specificity. The approach taken here is to establish a design optimisation framework that considers different tissue environment, the underlying engineering challenges of scaffolding in vivo, and the fluid and solid mechanics problems involved, using state-of-the-art computational tools including structural optimisation and inverse homogenisation. This project aims to address the following critical aspects in the design process of scaffold microstructure: i) Permeability of scaffold microstructure will be optimised towards the degree of anisotropy in the local microfluidic environment near the scaffold-host interface; ii) To improve the transport capacity of large scaffolds, a gradient transport property across the scaffold will be obtained by applying a gradient test field (macroscopically uniform but microscopically gradient); iii) An additional optimisation objective with respect to the minimisation of interfacial stress will be introduced, which not only dictates that the scaffold geometrically fits into the tissue cavity but also ensures that the interfacial stress caused by the possible relative movement between scaffold and the host tissue can be kept to a minimum; iv) A multi-objective optimisation scheme that takes into account the microenvironment of host tissue affected by both tissue-specific and patient-specific factors; v) The effective capacity of oxygen diffusion and nutrient supply in the scaffold microstructure will then be evaluated by an in silico mass diffusion model.

Project Outcome
The ultimate deliverable from this First Grant is a novel design optimisation tool for tissue scaffold. This tool will, for the first time, enable the scaffold microstructures to be designed towards individual and personalised use in vivo.

Clinical Relevance
The project also benefits from a clinical advisor who can provide not only additional sustainability to the programme and bring a new collaboration and clinical contacts from the NHS, but also the biomedical context to ensure that the implications of any simplifications can be addressed in future work.

Successful completion of this project would lead to a novel design tool that will significantly advance the development of the tissue-specific and patient-specific use of tissue scaffolds in vivo, and lead to critical scientific advances in translating tissue engineering into a clinically-adoptable technology. Apart from the academic impact that will be elucidated in the previous section, the beneficiaries of this research programme span from commercial end users and society in general to the people directly involved in the project work.

Commercial end users:
The proposed research has the potential to lead to patient-specific tissue scaffold designs, which is in line with the current development in personalised medicine in biomedical industry, and provides valuable information which can be used by tissue constructs manufacturers to direct and prioritise future R&D activities;

NHS:
By introducing key in vivo environment and patient-specific factors into the design optimisation process of tissue scaffolds, this project will pave a new avenue to advance tissue engineering from laboratory to clinics - an innovative approach to increase the efficacy of tissue constructs in clinical applications;

Quality of life:
Due to the generic nature of the proposed design framework for scaffold design, this project is also anticipated, as a long-term societal benefit, to contribute to the resolution of healthcare challenges in the UK in order to improve the quality of life.

People:
The transferrable skills including project management, development of computational tools, the attendance at key national and international conferences and new collaborations that may arise from the project will benefit both the PI and the PDRA throughout their career. This project will provide an essential platform on which the people involved will have the opportunities to develop themselves towards world-leading figures in tissue engineering and patient-specific modelling.