Scaffolds and Biofabrication for Bone Repair

Bone non-union fractures occur in 5-10% of all fractures and 20% of high energy fractures (Fig 4). There are complications in approximately half of the surgeries performed using the current autologous bone graft procedures. The need to find improved ways for bone healing has never been greater, due to the rising incidence of bony defects as a result of increasing fragility fractures in osteoporosis as the population ages, of trauma and of elective orthopaedic or other procedures.

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Figure 4: Issues with bone healing

We currently have in vitro assessed greater than 10 scaffolds for bone repair: naturally-derived and synthetic porous scaffolds from national and international collaborators. We have also developed novel nano-composite scaffolds incorporated with magnesium or strontium based nano-particles (Fig 5) that support mechanical strength as well as osteogenic properties.

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Figure 5: 3D Biofabrication of cartilage and bone constructs: A) CAD design, B) multiple print head 3D biofabrication setup, C) strontium- (scale bar = 1µm) and D) magnesium-based nano-particle synthesis (scale bar = 100nm), E) 3D Plotted degradable polymer-nanocomposite scaffolds for bone regeneration (scale bar = 1mm)

These scaffolds are also further combined with a range of hydrogel based bio-inks for cell and growth factor delivery. We have invented a unique visible light bio-ink that does not need exposure to ultra-violet (UV) light to 'harden' into 3D-bioprinted bone shapes like most other bio-inks used currently. Our bio-inks showed significantly higher viablity in human bone marrow-derived mesenchymal stem cells given that visible-light technology is gentler and more cell-friendly than UV light. With these newly developed bio-inks, we were able to print thick cell-laden constructs needed in surgery (Fig 6), with good long-term viability which is an impressive feat with important clinical impact as approaches using UV light are not able to achieve this scale.

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Figure 6: 3D Biofabrication of hydrogel constructs: A) CAD design of dome; B) 3D plotting of a large, 10mm thick porous dome scaffold using our novel visible light bio-ink (scale bar = 2mm); C) High print fidelity 3D plotted lattice scaffold (scale bar = 1mm); D) Stem cell laden biofabricated constructs show high viability (green fluorescence) after 21 days in vitro culture (scale bar = 100µm).

Furthermore, we have also applied our bio-ink chemistry to different biofabrication approaches such as stereolithography and microfluids. We have shown that complicated and sophisticated cell-laden hydrogel structures with high resolution (25 µm voxel size) can be fabricated using commercial stereolithography and digital light processing 3D Printing machines.

We have also established a pre-clinical bone defect model in which we have tested scaffolds with and without added growth factors. We have successfully tested three biomaterials from commercial partners, developed within New Zealand and the UK. The most successful bone growth scaffold contained lactoferrin demonstrating astounding re-growth after 12 weeks in the bone defect (Fig 7).

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Figure 7: Bone growth scaffold with lactoferrin

Further development has been undertaken to control the release of growth factors within the scaffold. We have developed synthetic hydrogels which degradation can be controlled from days to months, and growth factors can be covalently integrated within these gels.


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