Regenerating Tendons with Biodegradable Fibrous Scaffolds

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

Tendons come in many sizes and connect muscles and bones together. Being very strong they are able to withstand high loads. Unfortunately, tendons are commonly affected by disease, injuries and wear-and-tear, e.g. inflammatory tendonitis, if not rested can cause chronic pain and breakdown of the tendon tissue. Greater participation in sports and increasing number of older people, has led to a rise in tendon-associated problems. Several treatments are available, but they are not 100% successful. Common treatments include; surgery to stitch ruptured tendon-ends back together, but this can cause scar-tissue leaving the tendon prone to re-rupture. Tendons can also be repaired using tendon tissue that is taken from another site within the patient (autograft), or it can come from a human donor (allograft). However, in both cases the repaired tendon is left in a weakened state, which can lead to later problems. Also, patients who receive an autograft have longer recovery times and increased risk of infection because they now have two wounds; and those receiving allografts similarly have an increased risk of infection and chance of tissue rejection.

Using a biomaterials approach, we are aiming to provide a new and unique solution for tendon-associated problems. Biomaterials involves the use of approved-materials for implantation. These materials are formed into pre-designed structures, referred to as scaffolds, which imitate the tissue they are to replace. We have designed and developed a scaffold which closely imitates tendon structure and offers several advantages as a new tendon treatment:
1.Single surgery is required and creates no secondary wounds.
2.Risk of rejection is significantly reduced.
3.Load-bearing capabilities reduces patient recovery time.
4.Scaffold material breaks down at the same rate as new tendon-tissue formation leaving a new and fully repaired tendon.

During the last five-years, we have generated positive and encouraging scientific data regarding this scaffold, which includes a short-term preliminary study in mice. With DPFS-funding, we will further investigate the scaffold in this animal model as this will provide definitive results as to whether the scaffold provides good enough load-bearing support and promotes new tendon-tissue formation over time. We will also investigate ?up-scaling? this scaffold in terms of scaffold size and dimensions as this will allow scaffolds to be available in a range of sizes suitable for all patients with tendon injuries. After DPFS-funding we will commence a clinical trial, which will involve patients receiving this scaffold as a tendon treatment.

Technical Summary

Tendons, such as the Achilles and flexor, are affected by degenerative diseases, trauma and spontaneous rupture. There are approximately 400,000 total tendon procedures performed each year in Europe; and 550,000 cases of severed hand tendons reported annually in the USA. Currently, there are poor surgical procedures for injured tendons, and repair generally involves the formation of scar tissue, which is biochemically and biomechanically inferior to natural tendon tissue. This leaves the healed tendon prone to further injury. We propose an innovative tendon repair process involving biodegradable materials. We have developed 3D poly(?-caprolactone) scaffolds, which mimic the natural tendon tissue and have yielded positive results in tendon repair following a pilot animal study. This scaffold provides a novel device for use in regenerative tissue engineering of tendon and can be used in both augmention and reconstruction. The team has expertise in biology, engineering and clinical practice. With MRC funding, we intend to develop the scaffold through laboratory and pre-clinical studies leading to validation for clinical studies/commercialisation. This will require robust in-vitro and in-vivo data packages and the necessary commercialisation strategies and outputs. The surgical input into the project is an essential component of the study.

Publications

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Bhaskar P (2017) Cell response to sterilized electrospun poly(?-caprolactone) scaffolds to aid tendon regeneration in vivo. in Journal of biomedical materials research. Part A

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Bosworth L Characterising the effects of different sterilisation techniques on electrospun fibres in Transactions of the 26th Annual Conference of the European Society of Biomaterials

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Bosworth LA (2015) Optimizing Attachment of Human Mesenchymal Stem Cells on Poly(e-caprolactone) Electrospun Yarns. in Journal of visualized experiments : JoVE

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Bosworth LA (2013) State of the art composites comprising electrospun fibres coupled with hydrogels: a review. in Nanomedicine : nanotechnology, biology, and medicine

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Bosworth LA (2013) Investigation of 2D and 3D electrospun scaffolds intended for tendon repair. in Journal of materials science. Materials in medicine

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Bosworth LA (2014) Dynamic loading of electrospun yarns guides mesenchymal stem cells towards a tendon lineage. in Journal of the mechanical behavior of biomedical materials

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Bosworth, Lucy (2012) Fabricating Scaffolds of Electrospun Nanofibres from Synthetic Biopolymers for Tendon Repair in Transactions of the International Symposium on Ligaments and Tendons - XII, San Francisco, CA, USA February 3rd 2012

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Bosworth, Lucy (2012) Using Electrospun Nanofibrous Threads to Repair Tendons in Transactions of the Orthopaedic Research Society, San Francisco, CA, USA February 3rd - 7th 2012

 
Description MRC DPFS Grant
Amount £1,100,000 (GBP)
Funding ID G1000788 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2010 
End 06/2014