Organic/Inorganic Hybrid 'Bioinks' for 3D Bioprinting

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

With access to better healthcare and diet we are outliving our organs which at latter stages of life fail tragically leading to death if not transplanted on time. Therefore with increasing average age of the population, the number of people on the waiting list for an organ transplant increases, yet the amount of donors and available organs remains at a low. Currently, in the UK on average >1300 people per year either die whilst on the waiting list or became too sick to receive an organ transplant. Many more people are also suffering from limited or poor implant choices for repair and regeneration of tissue damaged from disease or trauma. To overcome this shortage of organs and the limitations of available implants several tissue engineering strategies have been explored. One promising approach is 3D bioprinting, which is a layer-by-layer fabrication technique for the production of implantation-ready organs and tissue patches using living cells, biomolecules and biomaterials.

Every organ is a complex structure of either hard (bone) or soft (skin, lung, heart, etc) tissues, and to some degree its structure and composition are unique to every person. Here, bioprinting is a promising technique for the production of organs and tissue patches that are a close mimic of the patient's own, within the operating theatre at the touch of a button. However, several key challenges exist before this becomes a reality. One major challenge is the development of new functional biomaterials also called "bioinks" for 3D bioprinting. Bioinks are an important part of bioprinting, they provide structural support and a safe environment for the living cargo. Current bioinks are made of soft hydrogels which: do not maintain the printed shaped very well; have poor mechanical properties at physiological conditions; and are of natural origin hence have an inherent batch-to-batch variation.

An ideal bioink should be fully synthetic and easily printable, have tuneable mechanical properties, and once implanted should produce a favourable host tissue-material interaction. We propose that this can be achieved by developing a silica-gel-based organic/inorganic hybrid bioink via a bio-friendly bottom-up process. Low temperature solution-based technique can be used to produce materials with a range of properties, from high strength bioactive glasses that form bond to bone to soft and flexible organic/inorganic hybrids that are suitable for cartilage and skin regeneration. First, we will develop novel precursors and investigate bio-friendly processing conditions to produce the bioinks. Then using a 3D printer produce tissues constructs resembling those of human tissues.

Planned Impact

The successful outcome of this project would have a significant societal and economic impact. Societal benefits will be to patients, healthcare professionals (orthopaedic and plastic surgeons) and services (e.g. the NHS). Economic benefits will be realised by patients, pharmaceutical and medical devices companies and also to the overall UK economy.

Two potential routes to impact:

The first route will benefit animal welfare, people and pharmaceutical companies within a 5-10 year timeframe. Annually, the pharmaceutical industry spends more than £30billion on research and development of new drugs, of the 5000+ drugs at the start of the pipeline only 20 are approved by the FDA. Majority of these drugs fail at the human testing stage resulting in not only a huge economic burden but also a negative societal impact. This research will contribute to the development of 3D in vitro models of human tissue which is a closer mimic of real tissue than 2D cultures and testing on small animals that could be used to test drugs and cosmetics. This has the potential to significantly impact on the speed, predictability and consequentially the cost of successful drug discovery. Additionally, this will also impact positively on the three Rs (replace, reduce and refine) in animals in research.

The second route would lead to both economic and societal impacts benefiting patients and healthcare professionals (orthopaedic and plastic surgeons) and healthcare services such as the NHS and also benefiting the UK economy. Currently, in the UK annually more than 180 000 hip and knee replacements and 25 000 bone graft operations are performed due to cartilage wear and bone related disease and trauma, respectively. Unfortunately, hip and knee implants eventually fail requiring revision surgery which cost the NHS 2-3 times its original operation. The bioinks developed in this research could be used to 3D bioprint constructs for osteochondral defects eliminating the need for implants and harvesting of autografts. Bioinks could also be tailored for production of skin grafts for wound healing that could aid in the healing of chronic wounds in over 200 000 patients in the UK costing >£2.3bn. On-demand manufacturing of near-patient, patient-specific implants and organs will deliver economic growth in UK and huge cost savings to the NHS and also save the lives and improve the quality of life for thousands of people.

The two most important outreach targets are researchers and clinicians. Findings will not only be published in peer reviewed journals and presented at international meetings they will also be conveyed directly to the beneficiaries of the research through collaborations, industrial project partners and public engagement activities. Engagements with researchers in the Centre for Innovative Manufacturing in: Regenerative Medicine, Medical Devices and Addictive Manufacturing will be initiated to foster wider use of bioinks developed in this research for various applications. Outreach programs targeted at clinicians and medical practitioners, introduced by our industrial partners, will be undertaken to create awareness on 3D bioprinting and near patient manufacturing techniques and its potential.
Progress will also be communicated to the general public by building on current media contacts and at open days.

Publications

10 25 50
 
Description We have produced and validated new chemicals which can be used to produce 3D printed tissues and organs. The new chemicals allow the production of new synthetic hydrogels (3D environment that resembles some of the native tissue where cell reside) which have improved mechanical properties to those currently available. We employed UK's National Facilities Diamond Light Source and Central Laser Facility to investigate the precursors and the hydrogels formed. Our studies have demonstrated that these systems are promising alternatives to hydrogels produced with natural biopolymers alone. These precursors will now we employed as bioinks and 3D extrusion printed to developed in vitro soft tissue.
Exploitation Route The precursors can be employed to produce hydrogels by anyone including researchers and industries attempting 3D extrusion printing of tissues and organs.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.birmingham.ac.uk/staff/profiles/clinical-sciences/Poologasundarampillai-Gowsihan.aspx
 
Description A collaboration which was started thanks to this project has lead to a patent filing. The patent deals with a technology development for real time imaging of 3D bioprinting. We are now exploring commercialisation opportunities and are in discussion with several bioprinter manufacturers.
First Year Of Impact 2020
Sector Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description The Great Britain Sasakawa Foundation Research Grant
Amount £3,600 (GBP)
Organisation The Great Britain Sasakawa Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2018 
End 07/2020
 
Description Development of polyol-modified-silanes precursors for 3D bioprinting 
Organisation University of Salzburg
Country Austria 
Sector Academic/University 
PI Contribution Developed several polyol-modified-silanes for 3D bioprinting. Tested their gel formation and gel properties at physiological conditions. Performed the first 3D printing of these organic/inorganic hybrid hydrogels.
Collaborator Contribution Knowledge and training on synthesis of polyol-modified silanes. Polyol-modified silanes solutions for experiments.
Impact Invited conference presentation at Nagoya Institute of Technology, Japan. This collaboration involves contributors with background in chemistry, materials science and cell biology.
Start Year 2016
 
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 MRC Harwell Open Day 2016 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 3D Bioprinting was displayed in the MRC Open day at Harwell. Together with 2 PhD students and a PDRA, tissue and organ printing was explained to school children, adults and pensioners using posters and 3D models. The highlight of the display was our own 3D printer which we used to print chocolate and plastics to demonstrate 3D printing.
Year(s) Of Engagement Activity 2016
URL https://www.mrc.ac.uk/about/events/mrc-festival-of-medical-research/mrc-festival-of-medical-research...