Manufacturing bespoke human organs; 3D printed nanocomposite trachea

Organ failure and tissue loss are challenging health issues due to widespread aging population, injury, the lack of organs for transplantation and limitations of conventional artificial implants. There is a fast growing need in surgery to replace and repair soft tissues such as blood vessels, stent, trachea, skin, or even entire organs, such as bladder, kidney, heart, facial organs etc. The high demand for new artificial implants for long-term repair and substantially improved clinical outcome still remains .Our well-publicised successes in using tissue-engineering to replace hollow organs in cases of compassionate need have shown the world that an engineering approach to hollow organ replacement is feasible, as well as serving to highlight those areas where more work is required to provide bespoke manufactured tissue scaffolds for routine clinical use Being able to replicate a functional part of one's body as an exact match and therefore to be able to replace it 'as good as before' is familiar in science fiction. Most implants will share limitations that are associated with either the materials used or the traditional way in which they have been made. With the advancement of additive manufacturing technology, 3D printing, biomaterials and cell production, printing an artificial organs is becoming a science and engineering fact and understandably can save lives and enhance quality of life through surgical transplantation of such printed organs produced on-demand, specifically for the individual of interest.

The project seeks to addresses the unmet need in traditional implants by exploiting our proprietary polymer nanocomposites developed at UCL and advanced digital additive manufacturing with surgical practice. we aim to develop a 3D advanced digital bio-printing system for polymer nanocomposites in order to manufacture a new-generation of synthetic soft organs 'on-demand' and bespoke to the patient's particular needs. Our extensive preclinical and on-going preclinical study on the nanocomposite-based organs will ensure the construct is able to induce angiogenesis and to perform function of an epithelium. Here we take these experiences in the compassionate case, and take trachea as an exemplar to develop a manufacturing method of producing bespoke tubular organs for transplantation with nanocomposite material.

This proposal will allow us to develop; a) a customer made 3D bioprinter with multi-printing heads and an environmental chamber which can print 'live' soft organs/scaffolds with seeded cells to meet the individual patients needs; b) a series of polymer nanocomposites suitable for 3D printingorgan constructs/host scaffolds; c) a formulations of bio-inks for printing cells, proteins and biomolecules. d) a printed artificial tracheal constructs using their radiographic images with optimised biochemical, biophysical and mechanical properties. e) Establishment of in-vivo feasibility data through observation of restoration of respiratory function and normal tissue integration of pig models which will be surgically transplanted

Clinical Impact
Live organ harvesting and transport, as well as the intensive care of critically ill patients and the loss of useful and healthy lives costs the UK and worldwide an inestimable amount in active resources. The successful outcome of this research proposal will enable manufacturing of tailor made organs for those require critical clinical attention and can potentially change the NHS surgical protocols for organ transplantation. This will shorten waiting times, allow early effective treatment, shorter hospital stay, and reduce or eliminate costs for direct hospital and palliative care costs, costs to the patient and loss of productivity e.g. employment (indirect costs). Therefore if this clinical need was to be successfully met, at a cost that was acceptable to society, not only will patient's benefit (reduced mortality/morbidity) but also national resources. Once we have established the exemplar protocol with this project it will catalyse the progress of a number of other tubular organ manufacturing to potentially have a greater impact.

3D printing/Rapid prototyping
Organ replacement is one of the supreme applications of 3D printing, which can really establish rapid prototyping as a key technology requirement not only in major surgical centres, but the spin of interest in what is possible with these techniques will rapidly establish this new technology as a norm. This will certainly have a significant impact on the manufacturers of this technology.

Capacity Building
This project will require training of RAs in multidisciplinary activities unique to this project and thus at the completion of the project will be great assets to the UK as well as internationally in terms of source of knowledge and experience. This manufacturing protocols developed in this research will interest many polymer manufacturing industry as well as instrument manufacturing industry (3D printing industry) who could use these developments to potentially establish a unique industry of tubular organ manufacturing for clinical applications, down the line and therefore should bring in a great deal of income to the country and create jobs for highly skilled individuals. Global medical implant industry such as Boston scientific has expressed their interest in being a partner in taking the end products to clinic and for commercialisation.

World leading research to meet national strategic needs
The applicants contribute to the national policies in applied regenerative science and technology through their representation in relevant select committee at the House of Lords (eg, Nov 2012) and the applicants continue to contribute to national policy making and the proposed developments should be of interest to be considered in the future development and encouraged for wider applications in regenerative medicine. Furthermore, the developments for bespoke manufacturing of implants should also bring solutions to those issues raised at the WHO, such as organ trafficking, transplantation tourism of organ and commercialism as highlighted in 'Declaration of Istanbul, 2008, WHO'