Flagship 6: Innovative new strategies for musculoskeletal & soft tissue repair

Principal Investigators

Professor Jillian Cornish, University of Auckland
Associate Professor Tim Woodfield, University of Otago

Associate Investigators

Dr David Musson, University of Auckland
Dr Dorit Naot, University of Auckland
Dr Ben Schon, University of Otago, Christchurch
Dr Khoon Lim, University of Otago, Christchurch

Clinical Partners

Prof Gary Hooper, Mr Jacob Munro, Mr John Ferguson, Mr Brendan Coleman, Mr Jeremy Simcock, Dr Ryan Gao, Dr Matthew Street

Summary

Skeletal tissue engineering represents a novel leap forward in clinical practice and a new frontier in skeletal medicine. This is a multidisciplinary field in its youth but it is expanding fast. Skeletal tissue engineering requires the presence of a biocompatible scaffold that supports cell growth and enhances the native tissue repair process.

The global tissue engineering and cell therapy market is destined to reach the US$ 20 billion mark at the end of 2015 and is envisaged to grow to over US$ 30 billion by 2018 with the largest segment (60% of the market) being orthopaedic/musculoskeletal applications (Fig 1).

A graph of global tissue engineering and cell therapy market in thousand million US dollars. It is increasing, from around six thousand million dollars in year 2009 growing to around 32 thousand million dollars in 2018. Orthopaedics and musculoskeletal are the largest group.

Figure 1: The global tissue engineering and cell therapy market

This project combines research expertise in bone, tendon and cartilage biology, with experience in translational in vitro and in vivo models. This is complemented by advanced technology platforms and expertise in 3D Printing and Biofabrication of scaffolds and multiscale computational modelling. Our multidisciplinary team of researchers and clinicians based at the partner universities enable development and application of translational regenerative medicine approaches for orthopaedic tissues. This unique research and training environment includes orthopaedic registrars, bioengineers and cell biologists working amongst senior clinicians and researchers at masters, PhD and postdoc level to deliver novel research capability for clinical and commercial application with industry partners. Our work involves constant feedback and discussions with orthopaedic surgeons and has led to multiple presentations at international conferences, publications in international journals of high repute, an orthopaedic registrar completing an excellent lab-based MSc and an orthopaedic registrar nearing the end of his outstanding lab-based PhD. In addition, two competent bioengineering students completed an MSc and a PhD in computational modelling.

The initial milestones, with an indication of current progress are:

1. 3D printed scaffolds for rotator cuff repair

Recurrent rotator cuff tears cost ~NZ$100m pa and heal poorly into functionally compromised fibrotic scar tissue (Fig 2). Tissue engineering has the potential to contribute to successful tendon healing; using a biomaterial scaffold inserted at the site of injury, providing temporary mechanical support, while ultimately enhancing tissue regeneration. We utilise advanced 3D Printing techniques to develop synthetic degradable scaffolds with hierarchical structures for rotator cuff repair. Due to unique processing technique, these flexible scaffolds have shown promising mechanical properties.

An illustration showing a rotator cuff tear.

Figure 2: Rotator cuff tear

2. In vitro assessment of scaffolds for bone repair

Several naturally-derived and synthetic porous scaffolds from national and international collaborators have undergone in vitro assessment using primary human bone cells (Fig 3). It is anticipated that these will move through to in vivo evaluation in a pre-clinical model. 3D Printing of nano-composite scaffolds and 3D Biofabrication of hydrogel bio-inks encapsulating bone marrow-derived stem cells have been developed (Figs 4 and 5) for bone regeneration which are undergoing in vitro characterisation.

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Figure 3: Human Bone Cells growing on a scaffold.

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Figure 4: 3D Biofabrication of Gelatin-MA hydrogel construct containing bone marrow stem cells

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Figure 5: 3D Printing of anatomically shaped cartilage-bone constructs

3. In vivo assessment of scaffolds for rotator cuff repair

UoA have used an in vivo model to successfully test two biomaterials from commercial partners, developed within New Zealand and the UK. We have also identified a collagen scaffold developed by the Ophthalmology Department, UoA, which is currently being patented for use in tissue regeneration (Fig 6). We are assessing this in our in vivo rotator cuff model and expect to report outcomes by the end of this year.

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Figure 6: Collagen scaffold (printed with permission from: Dr Dipika Patel, Ophthalmology, University of Auckland). A) Scanning electron micrograph B) fluorescent micrograph.

The Regenerative Medicine flagship programme aims to use biofabrication techniques, in-depth biological knowledge and expertise in a range of assessment tools to translate outcomes from promising research platforms into marketable therapeutic products. Throughout these milestones we constantly interact with clinicians and commercial entities within New Zealand and internationally. This platform research has strong people development, not only are we producing a platform for orthopaedic research training but also multidisciplinary biologists and bioengineers. We are using established basic principles and methodologies to perform this research and not developing new basic science. It is indeed translational research.