A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair

Abstract

Surgical reattachments of tendon to bone in the rotator cuff are reported to fail in around 40% of cases. There are no adequate solutions to improve tendon healing currently available. Electrospun, sub-micron materials, have been extensively studied as scaffolds for tendon repair with promising results, but are too weak to be surgically implanted or to mechanically support the healing tendon. To address this, we developed a bonding technique that enables the processing of electrospun sheets into multi-layered, robust, implantable fabrics. Here, we show a first prototype scaffold created with this method, where an electrospun sheet was reinforced with a woven layer. The resulting scaffold presents a maximum suture pull out strength of 167 N, closely matched with human rotator cuff tendons, and the desired nanofibre-mediated bioactivity in vitro and in vivo. This type of scaffold has potential for broader application for augmenting other soft tissues.

Introduction

Tears of the rotator cuff are a debilitating and painful condition that affects around 50% of the population over the age of 66, and their management represents a substantial and growing social and economic burden [1], [2]. Evidently, there is still no adequate solution for achieving a successful tendon repair, and conventional surgical repairs, where the tendon is attached to the bone using non-degradable suture and anchors, have been reported to fail in 20–90% of cases [3], [4], [5], [6]. Recent strategies, such as the augmentation of repairs with extracellular-based patches, have received mixed reports [7], [8]. A number of implants have been shown to elicit a severe foreign body response and inflammation, and in some cases fistulae formation, leading to poor repairs [9], [10], [11], [12], [13]. On the other hand, several extracellular-based scaffolds, in particular those not cross-linked during processing, have shown promising results in animal models and clinical trials [11], [14], [15]. However, overall, there is a lack of evidence as to the efficacy of many of these scaffolds [16], and they remain a very costly option. An alternative approach to the augmentation of rotator cuff repairs with extracellular-based scaffolds has been the use of synthetic materials. These traditionally manufactured textiles, produced by weaving, knitting, braiding or felting [17], [18], [19], [20], [21], [22], have proven safety records, based on long-term experience and extensive use in other surgical procedures, as well as the potential to be engineered into strong fabrics and provide mechanical support to the healing tissue [23], [24], [25]. Moreover, they may be designed as completely or partially degradable, thereby reducing the risk of long-term complications. However, there are mixed reports about the quality of their integration and ability to enhance healing and neo-tissue formation [6], [26], [27]. As a result, more biomimetic synthetic materials, which have the ability to promote tissue integration, have been sought.

Electrospun, sub-micron materials, produced by electrostatic dispersion of a polymeric fluid, have been extensively studied as experimental constructs for tissue engineering research and have been suggested as scaffolds for not only the repair of tendons [28], but also bone [29], cartilage [30], ligaments [31], liver [32], blood vessels [33] and nerves [34]. Electrospun materials show excellent in vitro performance in terms of cell attachment, spreading and differentiation, which is attributed to their morphology [35]. In particular, the diameter of the fibres produced using this technique, which is in the range of 0.05–5 μm [36], closely mimics the diameter and architecture of the fibres in the extracellular matrix (ECM). Three main variables: (1) fibre diameter, (2) chemistry and (3) fibre orientation, have been the focus of a large body of research undertaken to develop electrospun scaffolds. For example, a number of studies have shown that aligned scaffolds can modulate cell orientation, the expression of matrix proteins, and possibly cell re-programming through epigenetic modulators [37], [38], [39], [40]. Other studies have demonstrated that varying the chemistry of scaffolds by adding matrix components such as collagen and elastin can affect cell behaviour [41], [42], [43], [44]. Preliminary efficacy tests of synthetic degradable patches in animal models have also shown promising results, and aligned electrospun mats implanted in a rat model for up to 8 weeks were well-tolerated, with good cell infiltration [28]. However, although electrospun materials show excellent cell and tissue response, a major drawback is their poor mechanical properties, thought to be critical to the success of the surgical repair of tendons [45], [46]. Several strategies have been proposed to improve the mechanical properties of electrospun scaffolds, from attempts to improve the inherent strength of the material, through changing porosity, to better fibre arrangement, or post-treatments such as cross-linking, bonding and annealing [47], [48], [49], [50], [51]. In the context of tendon repair, those techniques offer only a marginal improvement in strength, and cannot mimic the mechanical properties of tendon tissue.

To overcome this issue, we developed a non-destructive and biocompatible bonding technique that enables the processing of electrospun sheets into multi-layers. We designed a prototype scaffold, where an aligned electrospun sheet was reinforced with a mechanically robust woven fabric. Both layers were made of polydioxanone (PDO), which was chosen based on an excellent record as a suture and a scaffold [52], [53], and previous feasibility studies from our group that demonstrated excellent compatibility with tendon cells, and detectability by ultrasound, which could enable localised injections of cells or growth factors post-surgery [54].

The design concept was to form a strong but bioactive implant made of biodegradable and biocompatible synthetic polymers. Overall, the aim of this study was to translate this design concept by manufacturing a prototype and evaluate it using an in vitro test system and an in vivo pre-clinical animal model.