Development of a braided electrospun suture to augment tendon repairs

Tendon tears are common and often require surgical repair. However, many surgical repairs fail, despite continued advances in surgical materials and techniques. Rotator cuff surgery, the clinical focus of this thesis, has particularly poor outcomes. Repair failure can be partially attributed to the inappropriate repurposing of sutures from use in other tissues, which fail to integrate with the specialised tendon tissue. The overall aim of this study was to develop a novel polydioxanone suture that has the potential to provide both biological and mechanical support to torn tendons. It is hypothesized that electrospun submicron fibres, which mimic native tendon extra-cellular matrix (ECM), can provide biological support to tendon. Meanwhile, larger and more robust melt-extruded microscale fibres can mechanically support surgical tendon repair. It is further hypothesized that a suture containing both electrospun and extruded fibres will overcome structural limitations associated with electrospun-only sutures, while still providing biological improvements over current sutures. This thesis describes a process to fabricate and evaluate translatable suture biomaterials deliberately designed for tendon, by engineering materials on the fibre, filament, and multifilament level. On the fibre level, annealing enables tailoring of the degradation rate of electrospun fibres, which could allow for biomaterial degradation kinetics to match new tissue deposition. On the filament level, melt-extruded materials had superior strength and stiffness to support surgical repair. Electrospun filaments had a higher surface area, porosity, and faster degradation rate, making them more suitable as biological support. On the multifilament level, industrial braiding enabled further control over suture size, porosity, and mechanical properties by altering braiding design and component ratios. A hybrid braided suture with an electrospun sheath and melt-extruded cores was designed to meet the demands of tendon: electrospun fibres on the outside approximate ECM and will be in contact with the biological milieu, while the melt-extruded fibres in the core provide prolonged mechanical support. The hybrid suture had a similar size and tensile strength to currently used sutures, but was less stiff and more porous. It induced differential serum protein binding and promoted more favourable tendon fibroblast attachment and proliferation, when compared to currently used sutures. This novel hybrid suture has potential to improve current treatment options for tendon repair. Future work should investigate its local surface properties, followed by a dynamic culture and in vivo study, to bring the device to the standard needed for pre-clinical and clinical trials. The design process and pipeline of characterisation methods developed in this thesis could be applicable and adaptable to biomaterials for other soft tissues in need of improved treatments

An in vitro study of the role of implant positioning on ulnohumeral articular contact in distal humeral hemiarthroplasty

Purpose: To investigate the effect of implant positioning on ulnohumeral contact using patient-specific distal humeral (DH) implants. Methods: Seven reverse-engineered DH implants were manufactured based on computed tomography scans of their osseous geometry. Native ulnae were paired with corresponding native humeri and custom DH implants in a loading apparatus. The ulna was set at 90° of flexion and the humeral component (either native bone or reverse-engineered implant) was positioned from 5° varus to 5° valgus in 2.5° increments under a 100-N compressive load. Contact with the ulna was measured with both the native distal humerus and the reverse-engineered DH implant at all varus-valgus (VV) angles, using a joint casting method. Contact patches were digitized and analyzed in 4 ulnar quadrants. Output variables were contact area and contact pattern. Results: Mean contact area of the native articulation was significantly greater than with the distal humeral hemiarthroplasty (DHH) implants across all VV positions. Within the native condition, contact area did not significantly change owing to VV angulation. Within the DHH condition, contact area also did not significantly change owing to VV angulation. Conversely, in the DHH condition, contact pattern did significantly change. Medial ulnar contact pattern was significantly affected by VV angulation. Lateral ulnar contact was variably affected, but generally decreased as well. Conclusions: Ulnar contact patterns were changed as a result of VV implant positioning using reverse-engineered DH implants, most notably on the medial aspect of the joint. Implant positioning plays a crucial role in producing contact patterns more like those observed in the native joint. Clinical relevance: Recent clinical evidence reports nonsymmetrical ulnar wear after DHH. This work suggests that implant positioning is likely a contributing factor and that more exact implant positioning may lead to better clinical outcomes

Host–biomaterial interactions in mesh complications after pelvic floor reconstructive surgery

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune cell-rich infiltrate, suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted and biomaterial properties of the mesh. This immune response might be strongly influenced by both the baseline inflammatory status of the patient, surgical technique and experience, and the unique hormonal, immune and microbial tissue niche of the vagina. Mesh porosity, surface area and stiffness also might have an effect on the immune and tissue response to transvaginal mesh placement. Thus, a regulatory pathway is needed for mesh development that recognizes the roles of host and biological factors in driving the immune response to mesh, as well as mandatory mesh registries and the longitudinal surveillance of patients

Synthetic sutures: clinical evaluation and future developments

Today's sutures are the result of a 4000-year innovation process with regard to their materials and manufacturing techniques, yet little has been done to enhance the therapeutic value of the suture itself. In this review, we explore the historical development, regulatory database and clinical literature of sutures to gain a fuller picture of suture advances to date. First, we examine historical shifts in suture manufacturing companies and review suture regulatory databases to understand the forces driving suture development. Second, we gather the existing clinical evidence of suture efficacy from reviewing the clinical literature and the Food and Drug Administration database in order to identify to what extent sutures have been clinically evaluated and the key clinical areas that would benefit from improved suture materials. Finally, we apply tissue engineering and regenerative medicine design hypotheses to suture materials to identify routes by which bioactive sutures can be designed and passed through regulatory hurdles, to improve surgical outcomes. Our review of the clinical literature revealed that many of the sutures currently in use have been available for decades, yet have never been clinically evaluated. Since suture design and development is industry driven, incremental modifications have allowed for a steady outflow of products while maintaining a safe regulatory position and limiting costs. Until recently, there has been little academic interest in suture development, however the rise of regenerative medicine strategies is shifting the suture paradigm from an inert material, which mechanically approximates tissue, to a bioactive material, which also actively promotes cell-directed repair and a positive healing response. These materials hold significant therapeutic potential, but could be associated with an increased regulatory burden, cost, and clinical evaluation compared with current devices

Using an industrial braiding machine to upscale the production and modulate the design of electrospun medical yarns

While electrospun multifilaments have shown initial promise as medical yarns, their development has been restricted to short sections of hand-braided yarns. Integrating electrospun material into existing industrial braiding production lines would enable the modulation of yarn properties and an increased production rate to meet the demand for clinical trials. In this study, we used an industrial braiding machine to manufacture multifilament polydioxanone yarns with various filament numbers and carrier arrangements. The resulting yarns were characterized by mercury porosimetry, mechanical and pull through testing and compared to clinically used braided Vicryl and monofilament polydioxanone (PDS) sutures. Electrospun yarns were significantly more porous (67%) compared with Vicryl (28%) and PDS sutures (0%), and possessed the classic toe region reminiscent of native tissue. Pull through testing revealed that the structural configuration of electrospun yarns allowed for more energy dissipation. These findings suggest that upscaling the production of braided yarns is critical for designing medical yarns with required properties for clinical applications

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

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 designed for the promotion of repair processes. Synthetic electrospun materials can mechanically support the tendon while providing topographical cues that regulate cell behavior. Here, a novel electrospun suture made from twisted polydioxanone (PDO) polymer filaments is compared to PDS II, a clinically used PDO suture currently utilized 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 analyzed 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 with PDS II, with relative enrichment of pathways including mTorc1 signaling and depletion of epithelial‐to‐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 while maintaining an appropriate tissue response

Early development of a polycaprolactone electrospun augment for anterior cruciate ligament reconstruction

Despite the clinical success of Anterior Cruciate Ligament reconstruction (ACLR) in some patients, unsatisfactory clinical outcomes secondary to graft failure are seen, indicating the need to develop new regeneration strategies. The use of degradable and bioactive textiles has the potential to improve the biological repair of soft tissue. Electrospun (ES) filaments are particularly promising as they have the ability to mimic the structure of natural tissues and influence endogenous cell behaviour. In this study, we produced continuous polycaprolactone (PCL) ES filaments using a previously described electrospinning collection method. These filaments were stretched, twisted, and assembled into woven structures. The morphological, tensile, and biological properties of the woven fabric were then assessed. Scanning electron microscopy (SEM) images highlighted the aligned and ACL-like microfibre structure found in the stretched filaments. The tensile properties indicated that the ES fabric reached suitable strengths for a use as an ACLR augmentation device. Human ACL-derived cell cultured on the fabric showed approximately a 3-fold increase in cell number over 2 weeks and this was equivalent to a collagen coated synthetic suture commonly used in ACLR. Cells generally adopted a more elongated cell morphology on the ES fabric compared to the control suture, aligning themselves in the direction of the microfibres. A NRU assay confirmed that the ES fabric was non-cytotoxic according to regulatory standards. Overall, this study supports the development of ES textiles as augmentation devices for ACLR

Anatomical considerations and biomechanics in distal humeral hemiarthroplasty: are custom-made implants essential?

Distal humerus hemiarthroplasty is a somewhat debated and relatively new therapeutic option for distal humerus fractures, their sequelae, and other humeral degenerative conditions associated with a preserved radioulnar compartment. The anatomical variability of the distal humerus is the main issue that remains to be solved, particularly in view of the limited modularity of the only implant currently available. The clinical relevance of the mismatch between the native joint and the replacement joint has yet to be clearly demonstrated in the long term, though biomechanical studies have highlighted marked ulnar cartilage wear associated with such implants. Clinical studies are needed to understand whether custom-made implants can improve the results yielded by the implant available at present