Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons

Abstract

Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies.Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO) has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies.Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:III collagen mRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106 neg CD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons.

Histological evaluation of cellular response to a multifilament electrospun suture for tendon repair

“…As mentioned earlier, there was also a large difference in diameter between the 3-0 control suture (0.3 mm) and the ES sutures (1.3 mm). We selected 3-0 sutures because they have a comparable strength to the ES sutures: their breaking force is reported to be around 50N [29,30], which matches our ES sutures (unpublished data). The larger resulting diameter for the ES suture is a necessary compromise to achieve a highly porous structure that enables cell infiltration, while permitting effective surgical use without breakage.…”

“…To create these biophysical cues in the suture material for tendon repair, aligned submicron fibres produced by electrospinning have shown promises [27][28][29][30]. These have the particularity of physically mimicking the native extracellular matrix structure and, as a consequence, of encouraging cell attachment, proliferation and differentiation (hence the term biophysical cues).…”

Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

“…The sample number is relatively low for the intact, tendinopathy and chronic rupture group, which might account for the less distinct regulations. To increase the sample number for intact tendons another tendon location could have been used, as performed in other studies [ 24 , 59 ]. However, we decided to use the same tendon as control to avoid regulations due to a different biomechanical stimulation of the tendons and surrounding tissues.…”

Augmenting endogenous repair of soft tissues with nanofibre scaffolds

“…However, the vast majority of studies have used 'healthy' cells, yet it is recognized that tenocytes isolated from tendon tears demonstrate an altered phenotype [168]. External biomechanical cues also influence the orientation [108] and proliferation rate of diseased rotator cuff tenocytes, but their response at the mRNA level does not precisely mirror that of healthy cells [165]. Clearly, when investigating the effects of biomechanical cues on tendon healing, the targeted tissue niche must always frame our enquires.…”