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Regener8 case study.


Figure 1. SEM micrographs comparing (a) fibre bundle of natural tendon tissue to (b) 3D electrospun polymer-1 fibre bundle.


Figure 3. SEM micrographs of polymer-1/solvent-2 with tenocytes cultured for 24 hrs demonstrating alignment and infiltration of the cells into the scaffold.


Figure 2. Tensile properties of 3D bundles – polymer-1/solvent-1, polymer-1/solvent-2, polymer-2/solvent-2 and polymer-1+2/solvent-2 – (a) Young’s Modulus, (b) ultimate tensile strength and (c) maximum strain. One-way ANOVA with Bonferroni post-tests; n=5. * p<0.05 and # not significant.


Figure 4. Histological examination of polymer-1/solvent-2 bundle versus autologous grafting. Implantation of bundle at (a) 1 week, (b) 3 weeks and (c) 6 weeks; grafting of autologous tissue at (d) 1 week, (e) 3 weeks and (f) 6 weeks. Scale bar represents 500 microns.


Importantly, we were able to develop a working protocol for embedding the tissue without compromising the material and sectioning the tissue and scaffold cleanly. Basic H&E staining showed a marked inflammatory response after one week for the grafted scaffold, which was on-going at three weeks. Cells were observed to have infiltrated deep within the scaffold after three weeks implantation, which was a positive outcome when considering new tissue ingrowth and blood vessel development. By six weeks, extensive remodelling of the scaffold had occurred and there was a significant cell response. Comparison to the ‘gold standard’ autograft – by one week the grafted tissue could be clearly distinguished between the cut tendon ends; after three weeks, the graft appeared to have integrated with the remaining tendon tissue and there was a notable cell response; at six weeks, the graft had fully integrated with the tendon tissue and it was difficult to differentiate between the two.


Future Developments: Regener8 funding has allowed this tendon regeneration project to progress further towards its long-term aims and provided a stepping stone to securing new, large-scale funding from the MRC Developmental Pathway Funding Scheme (DPFS).


This new, £1m three year MRC DPFS funding has allowed us to significantly strengthen the research team at The University of Manchester


This new, £1M three year MRC DPFS funding has allowed us to significantly strengthen the research team at The University of Manchester with the addition of Dr Sarah Cartmell (biomechanics/bioreactors), Dr Paul Mummery (imaging/modelling) and clinical guidance and direct input from Prof Gus McGrouther and Mr Jason Wong. The University Of Manchester Intellectual Property (UMIP) Ltd will also continue to support the team. The project will focus significantly on the biomechanics of the scaffold in vitro and in vivo and developing imaging techniques to quantify cell infiltration into the scaffold and assess scaffold integration in situ with the aim of developing a scaffold ready for clinical trials.


For more information on Regener8 funded projects visit www.regenr8.ac.uk/projects


www.regener8.ac.uk


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