Design of an electrospun tubular construct combining a mechanical and biological approach to improve tendon repair

Abstract

Hand tendon injuries represent a major clinical problem and might dramatically diminish a patient's life quality. In this study, a targeted solution for flexor tendon repair was developed by combining a mechanical and biological approach. To this end, a novel acrylate-endcapped urethane-based polymer (AUP) was synthesized and its physico-chemical properties were characterized. Next, tubular repair constructs were developed using electrospinning of the AUP material with incorporated naproxen and hyaluronic acid (i.e. anti-inflammatory and anti-adhesion compounds, respectively), and with a tubular braid as mechanical reinforcement. Tensile testing of the repair constructs using ex vivo sheep tendons showed that the developed repair constructs fulfilled the required mechanical properties for tendon repair (i.e. minimal ultimate stress of 4 MPa), with an ultimate stress of 6.4 ± 0.6 MPa. Moreover, in vitro biological assays showed that the developed repair tubes and the incorporated bioactive components were non-cytotoxic. In addition, when equine tenocytes and mesenchymal stem cells were co-cultured with the repair tubes, an increased production of collagen and non-collagenous proteins was observed. In conclusion, this novel construct in which a mechanical approach (fulfilling the required mechanical properties) was combined with a biological approach (incorporation of bioactive compounds), shows potential as flexor tendon repair application. Graphical abstract.

Graphical abstract

Fig. 1

Set-up of the tensile testing set-up of the repair construct on the ex vivo sheep tendon. Tensile testing set-up: A with ex vivo sheep tendon, clamping the tendon ends in the tensile machine, B without ex vivo sheep tendon, clamping the repair constructs’ end in the tensile machine

Fig. 2

Acrylate-endcapped urethane-based polymer (AUP) synthesis overview

Fig. 3

Measured swelling ratio and gel fraction of AUP530 at two different concentrations (i.e. 30 and 100 wt%)

Fig. 4

Visualization of a reinforced, drug-loaded ES repair construct. A Inner layer with no additional drugs that serves at enclosing the tubular braid in between two electrospun layers. B Tubular braid with a Chinese finger trap mechanism that acts as a mechanical support. C Outer layer with incorporated anti-adhesion and anti-inflammatory components. D Schematic visualization of the multi-layered repair construct. PCL was used as a reference

Fig. 5

Ex vivo tensile testing of the repair constructs using cadaveric sheep tendons (A) repair construct without reinforcement; B, C reinforced repair construct

Fig. 6

Degradation study of the electrospun AUP and PCL repair constructs in aqueous medium

Fig. 7

Cell viability of indirect (top) and direct (bottom) assay using hFBs, by a Ca-AM/PI staining at day 1, 3 and 7. (*p < 0.05). Tissue culture plastic was used as a positive control

Fig. 8

Production of total collagen (A, B) and non-collagenous proteins (C, D) illustrated in mono-cultures (tenocytes or mesenchymal stem cells, MSCs) and co-culture (tenocytes & MSCs) after an incubation of 7 days, including overall effects (B, D). Cells were cultured in direct contact with the electrospun constructs (PCL and AUP530:PCL). Tissue culture plastic was used as a positive control. (*p < 0.05)