An agile bio-manufacturing platform for production of blood vasculature

Lead Research Organisation: University of Birmingham
Department Name: Dentistry

Abstract

Nature is the prime example of complex and sophisticated manufacturing. The human body is constructed by cells and support matrices where a variety of biomolecules perform complex functions in development, normal function and regeneration. This delicate balance is disturbed in disease or trauma and confounded by the body's declining regenerative capacity with increasing age. Organ transplantation has saved many lives and millions of pounds to the NHS, however every day 4 people in the UK die while on the waiting list. Those fortunate to receive organ transplants require immunosuppressant drugs, making them prone to infection and increased risk of cancer. There is a dire need for artificially engineered organs and tissue grafts, that engraft successfully on implantation without the need for immunosuppression. Furthermore, cardiovascular disease is the top cause of death globally. This is caused by problems with the heart or the circulatory system. Transformative solutions are required to meet the rising unmet clinical need for organ transplantation and cardiovascular diseases.

The aim of this project is to develop an adventurous manufacturing workflow to recreate the structural and cellular complexity of blood vessels by employing novel manufacturing strategies. The project combines advanced materials, 3D printing and advanced imaging to provide transformative solutions to key healthcare challenges facing our aging society. This project will address the growing demand for functional tissue grafts and organs for transplantation and drug discovery. To date, a major hurdle in engineering artificial tissue has been the inability to reproduce the blood vessel micro- and macro-architecture.

Our novel manufacturing research idea is to develop a complex and sophisticated fluid delivery system, with a 3D printer to recreate blood vessels in the laboratory. Our research will enable the rapid production of blood vessels from small (width of hair) to large (centimetres) sizes, and harness advanced biomaterials, designed to change from solution to gel by mixing in the fluid delivery system, to achieve this goal.

Publications

10 25 50
 
Description Our team on the adventurous manufacturing project "An agile bio-manufacturing platform for production of blood vasculature" (EP/V051342/1) has been extremely productive, de-risking and generating several firsts in a short 1.5-year period. Our transformative achievements include:
- an innovative manufacturing pipeline (A1), novel fluidic chips (A2)5-6 and advanced hybrid materials (A3) to produce blood vessel mimics (A4) (Fig. 1). Our proposed follow-on will build on these extremely promising results to transform drug-discovery process by developing body-on-a-chip devices. These closely mimic human systemic physiology and thus enable early identification of inefficacious and toxic candidate compounds, thus saving costs, resources and time for a better sustainable and productive future.
- assembling and growing a team with established skillset in working together, productively. Looking ahead, we have retained the talent pool and expanded it with new members and partners with complementary skillsets in biology, manufacturing and innovation to collectively deliver the proposed project.
Exploitation Route We have submitted a follow-on proposal to EPSRC to continue this work.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Epithelial barrier model: in silico modelling and high throughput assessment
Amount £200,000 (GBP)
Funding ID NC/X002322/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Public
Country United Kingdom
Start 02/2023 
End 01/2025
 
Description LiSaN-BioFab: A Combined Manufacturing And Imaging Facility For The Development Of Engineered Organs
Amount £10,000 (GBP)
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2021 
End 12/2022
 
Description Manipulating cellular functions using ceramic materials 
Organisation Nagoya Institute of Technology
Department Institute of Ceramics Research and Education
Country Japan 
Sector Academic/University 
PI Contribution Novel sol-gel process for the production of bioactive glass fibres.
Collaborator Contribution Electrospinning technique and synthesis of bioactive glass fibres for use in bioinks.
Impact Successful beamtime application via Diamond Light Source for X-ray tomographic imaging. Published manuscript titled "X-ray tomographic imaging of tensile deformation modes of electrospun biodegradable polyester fibres".
Start Year 2015
 
Description Real-time imaging of bioprinting 
Organisation Polytechnic University of Milan
Country Italy 
Sector Academic/University 
PI Contribution We were provided access to light-sheet imaging facilities via the LaserLab EU scheme.
Collaborator Contribution Alessia Candeo our collaborator performed all the imaging and supported data analysis.
Impact - Successfully obtained beamtimes via LaserLab EU and Central Laser Facility. This accounts for over £50,000 in in-kind contributions. - Published a paper in Bioprinting Journal. - Submitted a EU Horizon and a Wellcome Trust technology development application and am waiting for decisions on a proposal submitted to EPSRC.
Start Year 2018