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Regener8 case study. Regener8 Case Study: Regenerating

tendons using electrospun fibrous scaffolds By Lucy Bosworth and Sandra Downes, Material Science Centre, The University of Manchester

The Problem: Within Europe approximately 400,000 total tendon procedures are performed each year; and in the USA, 550,000 cases of severed hand tendons are reported annually. Current interventions commonly do not facilitate acceptable tendon healing – scar tissue often results, which leaves the tendon both biochemically and biomechanically inferior and susceptible to further tissue damage and rupture. Consequently, there is scope to develop a new therapy for repair of damaged tendons.

The Solution: Our approach is to incorporate the use of biomaterials to create an acellular, biodegradable scaffold, which mimics the tendon ultrastructure, provides sufficient tensile properties and is naturally resorbed by the body at a rate that matches the speed of new tendon tissue formation.

The Technology: Tendons are highly fibrous tissues and in order for us to replicate their natural structure, we adopted the electrospinning technique – known for it’s high fibre output – to fabricate our scaffolds. 2D ribbons of aligned fibres collected from the edge of a rotating mandrel are twisted to create 3D fibrous bundles, which mimic the hierarchical bundles within tendons (Fig.1).

Research Findings: Regener8 funding allowed us to focus on a series of polymer/solvent combinations and how the action of the solvent affected material properties, particularly the mechanical profile. The results showed a marked increase in tensile properties of the 3D bundles, particularly for the polymer-1/solvent-2 combination (Fig.2). Fibre morphology demonstrated relatively uniform, smooth fibres, whereas fibres from the original polymer-1/solvent-1 mixture contained a high volume of beading (unwanted by-product) in amongst

A healthy section of the flexor digitorum longus tendon located within the hindpaw was excised and a single 3D bundle then grafted into this partial defect.

the nanofibres. Presence of this beading (i.e. defects) will have contributed greatly to the poor tensile properties obtained for this particular polymer/solvent system.

Assessment of cell response to the polymer-1/solvent-2 system remained relatively unchanged – tenocytes (main tendon cell type) aligned and proliferated parallel to the main fibre axes and appeared to infiltrate the scaffold after 24hrs in culture (Fig.3).

With a scaffold structure that closely mimics the natural tendon tissue, guides the tendon cells to align in a single direction, and with significantly improved tensile properties, the scaffolds were assessed in vivo using a mouse model developed by Prof. Gus McGrouther’s group. A healthy section of the flexor digitorum longus tendon located within the hindpaw was excised and a single 3D bundle then grafted into this partial defect. The grafted scaffold was held in place by surrounding soft tissues and left for up to six weeks. As a positive control, the excised tendon tissue was implanted into the other hindpaw of the same mouse (i.e. tissue excised and autologous tendon tissue implanted).

Observations made during this time determined the mice to be healthy and they did not appear to be irritated by the implantation of synthetic material. Histological assessment was performed at one, three and six week’s post-implantation and compared to autograft (Fig.4).


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