Microfluidic fibre extrusion for bone replacement

In most cases, when a young person breaks a bone, it tends to heal quickly and efficiently.

As people get older, there are more problems associated with their bones:
- Older bones are more prone to fracture
- Joints become painful as a result of wear and tear
- Older people are less agile and therefore more prone to have an accident that can result in bone breakage
- Older broken bones heal more slowly than young bones
- The reduced mobility that is associated with waiting for bones to heal, reduces agility further.....................

In the UK, we have a low birth rate and people are tending to live longer. Thus, our population is ageing at a rapid rate and so all of the problems outlined above become more pressing.

There has been much progress in the field of biomaterials in attempts to produce materials for bone therapies to address some of these problems. However, ideal solutions continue to evade us.

In Nature, living systems produce mineral structures like bones, teeth and shells by bringing together organic and inorganic materials. Engineers have clever tools such as microfluidics that enable reactions to be carried out on a minute scale.

This project aims to test whether or not microfluidics can be used to produce organic fibres with mineral associated (just like in Nature). The mineral-fibre complex could then be used as a temporary scaffold that would encourage the body to produce new bone, thus forming the ultimate bone therapy material.

1. Use microfluidics to extrude polymers: collagen, polycaprolactone (PCL) and polylactic acid (PLA) in isolation and in combination (fibre composites)
2. Fibre composites will be prepared with each combination and permutation of the three polymers in terms of which are present and their location within the fibre
3. Grow mineral crystals (apatite) along with the polymer fibres and monitor crystal maturation in real time using in situ Raman
4. Use scanning electron microscopy (SEM) to quantify the number and location of mineral crystals with each fibre composite
5. Correlate data from 3 back to the precise conditions at any given point along the microfluidic channel
6. Test the material properties and biodegradability of these composites and use this knowledge to refine our selection of reaction conditions to exclude those that are less suitable in terms of physical and material properties or degradability
7. Test the response of mesenchymal stem cells (MSCs) to these composites. Cellular response will be quantified in terms of attachment, spreading and production of bone markers, stem cell markers (stro-1) and other phenotypical markers will be quantified
8. Use the knowledge in 4-7 to exploit the precise control afforded by microfluidics to refine selection of conditions used to produce potential bone therapy materials via this approach

Who will benefit?
The project will contribute to the fields of biomaterials, biomineralisation, cell engineering and materials science. Scientists in all of these fields will benefit as well as research-active clinicians. Although this is s proof-of-concept project, ultimately, medical practitioners and, of course, patients will be the true beneficiaries.

How will they benefit?
Demonstrating the feasibility of using microfluidics in this way will, in due course, provide a novel technique for tuneable biomaterial production. The high throughput system will ensure that an extensive suite of conditions is tested with precise detail of reaction conditions available and sufficient feedback loops to enable refinement of the process for predictable cellular response and material properties.

Ensuring that they do benefit
While this project aims to provide the fundamental knowledge to assess the suitability of this approach, follow-on funding to see it through to application may be required. Nonetheless, all available opportunities for commercial exploitation will be sought and the potential to 'spin out' the findings will be actively pursued through close links with Scottish Enterprise, Glasgow.
Glasgow Orthopaedic Research Initiative (GLORI) provides us with ideal access to a community of academics and clinicians that will ensure that our approach is directed towards application from the outset.
Although this is only a 12 month project, with such a range of disciplines, it is particularly important that dissemination of findings occurs at conferences and in high impact journals across all of these subjects to ensure that academic and clinical impacts are maximised and that findings are not restricted to discipline silos.

Wider dissemination
All of the applicants are keen to work with the BBSRC to publicise the approach and findings here and we intend to write an article for a popular journal such as New Scientist and Materials World