In vitro evaluation of the response of human tendon-derived stromal cells to a novel electrospun suture for tendon repair.

Andrey Nezhentsev,Mathew J Baldwin,Pierre‐Alexis Mouthuy,Andrew J Carr,Mark Isaacs,Jolet Y Mimpen,Roxanna E Abhari,Edyta Augustyniak,Sarah J B Snelling

doi:10.1002/tsm2.233

Andrey Nezhentsev, Mathew J Baldwin + Show 7 more

Open Access

https://doi.org/10.1002/tsm2.233

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Abstract

Recurrent tears after surgical tendon repair remain common. Repair failures can be partly attributed to the use of sutures not designed for the tendon cellular niche nor for the promotion of repair processes. Synthetic electrospun materials can mechanically support the tendon whilst providing topographical cues that regulate cell behaviour. Here, a novel electrospun suture made from twisted polydioxanone (PDO) polymer filaments is compared to PDS II, a clinically-used PDO suture currently utilised in tendon repair. We evaluated the ability of these sutures to support the attachment and proliferation of human tendon-derived stromal cells using PrestoBlue and Scanning Electron Microscopy. Suture surface chemistry was analysed using X-ray Photoelectron Spectroscopy. Bulk RNA-Seq interrogated the transcriptional response of primary tendon-derived stromal cells to sutures after 14 days. Electrospun suture showed increased initial cell attachment and a stronger transcriptional response compared to PDS II, with relative enrichment of pathways including mTorc1 signalling and depletion of epithelial mesenchymal transition. Neither suture induced transcriptional upregulation of inflammatory pathways compared to baseline. Twisted electrospun sutures therefore show promise in improving outcomes in surgical tendon repair by allowing increased cell attachment whilst maintaining an appropriate tissue response.

Highlights

Tendon injuries are common and cause pain and reduced quality of life for patients
While electrospun and PDS II sutures are both made of PDO, these results show that tendon-derived stromal cells cultured on these sutures have significant differences in attachment and transcriptional response
We demonstrated that electrospun sutures induced a distinct and stronger tendon-derived stromal cell transcriptomic response when compared to PDS II sutures

Summary

| INTRODUCTION

Tendon injuries are common and cause pain and reduced quality of life for patients. Rotator cuff tendon tears alone affect around 50% of those over 66 years of age,[1] and many of these patients require surgical repair.[2]. The use of sutures that enable cellular attachment and proliferation, and that do not raise a chronic inflammatory response may improve the efficacy of tendon repair.[5] Electrospun materials show particular promise and can be produced from synthetic and clinically approved materials, including polydioxanone (PDO), which is an absorbable polymer used to produce PDS II sutures currently deployed in tendon repair. The overarching aim of this in vitro study was to assess the potential of twisted electrospun PDO sutures in tendon repair This builds on our previously published work[13,19] and uses a modified electrospun suture that ensures uniformity of fiber diameter, and a high tensile strength and hierarchical structure that have potential to both mechanically and biologically support repair. We hypothesized that a twisted electrospun suture would promote tendon-derived stromal cell attachment and proliferation and induce a pro-reparative gene expression profile

| MATERIALS AND METHODS

| RESULTS

| DISCUSSION

Findings

| CONCLUSIONS