Additively manufacturing a new generation of super medical devices
In the next of our blogs from speakers at this year's Additive International conference, the University of Nottingham’s Professor Ricky Wildman looks at how recent advances in additive manufacturing technology could enable the development of a new generation of bio-instructive medical devices able to directly control cell behaviour.
There is often considerable excitement with additive manufacturing in bioprinting, with plentiful exploration of new designs and shapes, but success is often a matter of luck in finding a good design and we lack a nuanced understanding of the structure-function relationships that would enable us to create good designs.
Recently, we have started to ask the question of how additive manufacturing could be used to unravel these structure-function relationships and how it could be used to create devices that we are able to control at the biological level. This has coincided with developments in commercially available high-resolution systems and the adoption of approaches that allow for spatially and temporally distributed composition.
At the same time, there has been an effort to create libraries of materials that have bioinstructive properties (i.e., properties that result in a directed or designed-in change in behaviour of cells). Such materials might, for instance, reduce or increase the attachment likelihood of microbes to a surface, or they may induce a phenotypic change in mammalian cells. These advances have recently been brought together to explore how we might control cell behaviour, defeating antimicrobial resistance and infection, and promoting wound healing.
Alongside this, significant advances in computational design - including artificial intelligence and design optimization - are giving us the opportunity to identify the best material and device designs very quickly.
Two examples of this are developments that operate at different length scales, but ultimately could be brought together to create highly optimised, personalisable, multi bioinstructive composite devices.
Ink jet based 3D printing is a drop on demand approach, that allows for multimaterial deposition over wide areas. The development of ink jet printable bioinstructive materials allows us to design and create devices that resist bacterial attachment, (i.e. do not rely on elution of antimicrobials that lead to antimicrobial resistance). It is now possible to select from a library of materials, each with a different modulus, to create a multimaterial device with designed-in spatially varying compliance, whilst also retaining the antibiofilm properties. This is possible because we can use genetic algorithms to decide where and when to place materials with different properties, allowing us to generate, for example, finger prosthetics that flex where needed, but are stiff where it interfaces with the bone.
Secondly, high resolution techniques, such as two photon polymerization or projection micro stereolithography, allow us to pattern surfaces with intricate shapes in the nano-micro size range. In a similar way to how ‘shark skin’ is emulated to reduce bacterial attachment, we can populate surfaces with complex architectures that are tailored to drive a particular cell response. We know that both microbial and mammalian cells respond to topology, chemistry and stiffness. Additive manufacturing gives us the ability to target each of those independently or ‘orthogonally’ – we can choose to change shape, or material independently – and we can even vary each of these qualities spatially over a surface or an object. This gives us considerable power over cell behaviour, particularly if we know the structure-function relationship that tells us how a cell will change with respect to each of these qualities. Once we know this, we will be able to design surfaces, and devices, that will allow us to stop infection at wound sites or speed up bone growth after fractures.
In the future -as these techniques become translated and scalable manufacturing systems capable of high throughput -we will be able to tailor devices at both the micro and the macro scales, and also ‘dial up’ properties to specify exactly how we want biology to respond, giving us the opportunity to create additively manufactured super medical devices.