3D printing multifunctional devices without internal interfaces for cartilage repair
Lead Research Organisation:
Imperial College London
Department Name: Materials
Abstract
We aim to create the first "inks" that can be used in additive manufacturing (vat based stereolithography) to produce complex architectures with stiffness and compositions gradients without any joins or internal interfaces. While this technology will have a wide range of applications, we will first use it to fulfil an unmet clinical need in orthopaedic surgery: devices that can heal damaged cartilage.
Currently, there are very few, if any, materials that exist that have a true continuous composition or stiffness gradients. There are certainly none that have good mechanical properties. Sol-gel hybrid materials are assembled of intimately mixed co-networks of organic and inorganic components, but above the nanoscale they appear as single materials, distinguishing them from composite materials. Importantly, we have shown in our pilot studies that we can layer sol-gel materials as viscous liquids, just before they gel, so forming single materials with no internal joins or interfaces. We have 3D printed them, but only as grid-like architectures. Here, we will develop new hybrid inks that can be used to make complex pore architectures in vat based stereolithography (SLA), for the first time.
Damage to articular cartilage due to sports injuries, trauma or age-related wear are increasingly likely as an active population ages. Current best practice for regeneration of small defects in knee cartialge is microfracture, which involves making small holes into the underlying bone to liberate the marrow, which fills the defect with weak fibrous cartilage. The cartilage only lasts 2-5 years before the procedure must be repeated. Eventually, total joint replacements are needed, which are major operations that involve removing a lot of tissue, and only last 15-25 years. Alternative medical devices are needed, e.g. using advanced materials with specifically designed chemistry and architecture. If successful, we can then apply the technology to help combat arthritis, something that effects everyone as they age.
Our current 3D printed hybrid material shows great potential for regenerating cartilage because it provokes stem cells to produce articular cartilage-like matrix, rather than functionally inferior fibrocartilage. Importantly its mechanical properties can match that of the cartilage and transfer mechanical cues to the cells growing within it, which is critical for generation of high-quality cartilage. However, our previous 3D printing technique could only produce log-pile structures. The architecture of the device needs to be more complex. As cartilage is thin, most defects penetrate deep into the underlying bone, so we have designed a device that we hypothesise can regenerate the bone and the cartilage in appropriate locations. The part that goes into the bone will also be important for ensuring the implant stays in place during healing. Novelty of the research includes: the architectural design of the implant; the materials used to make it (new sol-gel hybrids that can be used in SLA) and the fact that sol-gel hybrids will be 3D printed in complex architectures (using SLA) for the first time.
Following cell studies to show appropriate stimulus is provided to stem cells to send them down the required route (bone or cartilage), and ensuring potential for vascularized bone ingrowth, preclinical studies will be carried out. Our project partners will assist in technology transfer: Evonik and Makevale will produce the polymeric raw materials and Smith and Nephew will assess market potential, identify translation milestones and test our optimised device in their arthritis sheep model.
This proposal will benefit medical device companies, patients, orthopaedic surgeons, and health services (e.g. the NHS) in a 10-20 year timeframe. As a third of workers are now over 50, it is critical that health services have access to technology that can allow patients to return to work quickly and reduce numbers of revision surgery.
Currently, there are very few, if any, materials that exist that have a true continuous composition or stiffness gradients. There are certainly none that have good mechanical properties. Sol-gel hybrid materials are assembled of intimately mixed co-networks of organic and inorganic components, but above the nanoscale they appear as single materials, distinguishing them from composite materials. Importantly, we have shown in our pilot studies that we can layer sol-gel materials as viscous liquids, just before they gel, so forming single materials with no internal joins or interfaces. We have 3D printed them, but only as grid-like architectures. Here, we will develop new hybrid inks that can be used to make complex pore architectures in vat based stereolithography (SLA), for the first time.
Damage to articular cartilage due to sports injuries, trauma or age-related wear are increasingly likely as an active population ages. Current best practice for regeneration of small defects in knee cartialge is microfracture, which involves making small holes into the underlying bone to liberate the marrow, which fills the defect with weak fibrous cartilage. The cartilage only lasts 2-5 years before the procedure must be repeated. Eventually, total joint replacements are needed, which are major operations that involve removing a lot of tissue, and only last 15-25 years. Alternative medical devices are needed, e.g. using advanced materials with specifically designed chemistry and architecture. If successful, we can then apply the technology to help combat arthritis, something that effects everyone as they age.
Our current 3D printed hybrid material shows great potential for regenerating cartilage because it provokes stem cells to produce articular cartilage-like matrix, rather than functionally inferior fibrocartilage. Importantly its mechanical properties can match that of the cartilage and transfer mechanical cues to the cells growing within it, which is critical for generation of high-quality cartilage. However, our previous 3D printing technique could only produce log-pile structures. The architecture of the device needs to be more complex. As cartilage is thin, most defects penetrate deep into the underlying bone, so we have designed a device that we hypothesise can regenerate the bone and the cartilage in appropriate locations. The part that goes into the bone will also be important for ensuring the implant stays in place during healing. Novelty of the research includes: the architectural design of the implant; the materials used to make it (new sol-gel hybrids that can be used in SLA) and the fact that sol-gel hybrids will be 3D printed in complex architectures (using SLA) for the first time.
Following cell studies to show appropriate stimulus is provided to stem cells to send them down the required route (bone or cartilage), and ensuring potential for vascularized bone ingrowth, preclinical studies will be carried out. Our project partners will assist in technology transfer: Evonik and Makevale will produce the polymeric raw materials and Smith and Nephew will assess market potential, identify translation milestones and test our optimised device in their arthritis sheep model.
This proposal will benefit medical device companies, patients, orthopaedic surgeons, and health services (e.g. the NHS) in a 10-20 year timeframe. As a third of workers are now over 50, it is critical that health services have access to technology that can allow patients to return to work quickly and reduce numbers of revision surgery.
Publications
Heyraud A
(2023)
3D printed hybrid scaffolds for bone regeneration using calcium methoxyethoxide as a calcium source
in Frontiers in Bioengineering and Biotechnology
Jaggard MKJ
(2023)
The effect of liquid-liquid extraction on metabolite detection and analysis using NMR spectroscopy in human synovial fluid.
in Journal of pharmaceutical and biomedical analysis
Description | Translation of Bouncy Bioglass towards Spinout |
Amount | £68,415 (GBP) |
Funding ID | EP/X52556X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2022 |
End | 11/2023 |
Description | Medical devices for cartilage regeneration |
Organisation | Orthox Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Orthox are interested in commercialising our scaffolds for cartilage regeneration. We have provided technical input and shared our data under a non disclosure agreement |
Collaborator Contribution | Input into design of device, development of technology for surgical delivery and advise on technology transfer strategy. |
Impact | No outputs yet |
Start Year | 2023 |
Description | Magazine Article |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Article for February 2024 issue of National Geographic. Julian Jones assisted the author with the scientific content, based on Bouncy Bioglass. Francesca Tallia and Agathe Heyraud provided samples for photography and assisted with the photo shoot. |
Year(s) Of Engagement Activity | 2024 |
URL | https://www.nationalgeographic.com/magazine/issue/february-2024 |