Search

Background Retearing after rotator cuff surgery is a major clinical problem. Numerous scaffolds are being used to try to reduce retear rates. However, few have demonstrated clinical efficacy.We hypothesize that this lack of efficacy is due to insufficient mechanical properties. Therefore, we compared the macro and nano/micro mechanical properties of 7 commercially available scaffolds to those of the human supraspinatus tendons, whose function they seek to restore. Methods The clinically approved scaffolds tested were X-Repair, LARS ligament, Poly-Tape, BioFiber, GraftJacket, Permacol, and Conexa. Fresh frozen cadaveric human supraspinatus tendon samples were used. Macro mechanical properties were determined through tensile testing and rheometry. Scanning probe microscopy and scanning electron microscopy were performed to assess properties of materials at the nano/microscale (morphology, Young modulus, loss tangent). Results None of the scaffolds tested adequately approximated both the macro and micro mechanical properties of human supraspinatus tendon. Macroscale mechanical properties were insufficient to restore load-bearing function. The best-performing scaffolds on the macroscale (X-Repair, LARS ligament) had poor nano/microscale properties. Scaffolds approximating tendon properties on the nano/microscale (BioFiber, biologic scaffolds) had poor macroscale properties. Conclusion Existing scaffolds failed to adequately approximate the mechanical properties of human supraspinatus tendons. Combining the macroscopic mechanical properties of a synthetic scaffold with the micro mechanical properties of biologic scaffold could better achieve this goal. Future work should focus on advancing techniques to create new scaffolds with more desirable mechanical properties. This may help improve outcomes for rotator cuff surgery patients.

Annealing, or heat treatment, has traditionally been used as a treatment to improve the strength and stiffness of electrospun materials. Understanding the extent to which annealing can improve the mechanical properties and alter the degradation rate of electrospun polydioxanone filaments could influence the range of its potential clinical applications. In this study, we investigated the effect of annealing electrospun polydioxanone filaments at varying times and temperatures and subsequently subjecting them to in vitro degradation in phosphate buffer saline for up to 6 weeks. Fibre alignment, tensile strength and thermal properties were assessed. It was determined that annealing at 65˚C for 3 hours only marginally improved the tensile strength (9±2%) but had a significant effect on reducing strain and rate of degradation, as well as maintaining fibre alignment within the filament. The filament retained significantly more of its force at failure after 4 weeks (82±15%, compared to 61±20% for non annealed filaments) and after 6 weeks of degradation (81±9%, compared to 55±13% for non annealed filaments). Conversely, annealing filaments at 75˚C improved the initial tensile strength of the filament (17±6%), but over 6 weeks, both samples annealed at 75˚C and 85˚C otherwise performed similarly or mechanically worse than those not annealed. These findings suggest that annealing at low temperatures is more useful as a method to tailor degradation rate than to improve mechanical properties. The ability to modulate the degradation profile with annealing may become useful to tailor the properties of electrospun materials without altering the chemistry of the polymer used. This might better match the degradation of the implant and gradual loss of mechanical properties with the new matrix deposition within the structure, enabling multiple regenerative strategies within a single biomaterial system.

High initial fixation strength, mechanical stability and biological healing of the tendon-to-bone interface are the main goals after rotator cuff repair surgery. Advances in the understanding of rotator cuff biology and biomechanics as well as improvements in surgical techniques have led to the development of new strategies that may allow a tendon-to-bone interface healing process, rather than the formation of a fibrovascular scar tissue. Although single-row repair remains the most cost-effective technique to address a rotator cuff tear, some biological intervention has been recently introduced to improve tissue healing and clinical outcome of rotator cuff repair. Animal models are critical to ensure safety and efficacy of new treatment strategies; however, although rat shoulders as well as sheep and goats are considered the most appropriate models for studying rotator cuff pathology, no one of them can fully reproduce the human condition. Emerging therapies involve growth factors, stem cells and tissue engineering. Experimental application of growth factors and platelet-rich plasma demonstrated promising results, but has not yet been transferred into standardized clinical practice. Although preclinical animal studies showed promising results on the efficacy of enhanced biological approaches, application of these techniques in human rotator cuff repairs is still very limited. Randomized controlled clinical trials and post-marketing surveillance are needed to clearly prove the clinical efficacy and define proper indications for the use of combined biological approaches. The following review article outlines the state of the art of rotator cuff repair and the use of growth factors, scaffolds and stem cells therapy, providing future directions to improve tendon healing after rotator cuff repair. Level of evidence Expert opinion, Level V.

Background All surgical meshes entering the U.S. market have been cleared for clinical use by the 510(k) process of the Food and Drug Administration (FDA), in which devices simply require proof of “substantial equivalence” to predicate devices, without the need for clinical trials. However, recalled meshes associated with adverse effects may, indirectly, continue to serve as predicates for new devices raising concerns over the safety of the 510(k) route. Methodology Here we assess the potential magnitude of this problem by determining the ancestral network of equivalence claims linking recently cleared surgical meshes. Using the FDA website we identified all surgical meshes cleared by the 510(k) route between January 2013 and December 2015 along with all listed predicates for these devices. Using a network approach, we trace the ancestry of predicates across multiple generations of equivalence claims and identify those meshes connected to devices that have since recalled from the market along with the reason for their recall. Conclusions We find that the 77 surgical meshes cleared between 2013 and 2015 are based on 771 interconnected predicate claims of equivalence from 400 other devices. The vast majority of these devices (97%) are descended from only six surgical meshes that were present on the market prior to 1976. One of these ancestral meshes alone, provided the basis of 183 subsequent devices. Furthermore, we show that 16% of recently cleared devices are connected through equivalence claims to the 3 predicate meshes that have been recalled for design and material related flaws causing serious adverse events. Taken together, our results show that surgical meshes are connected through a tangled web of equivalency claims and many meshes recently cleared by the FDA have connections through chains of equivalency to devices which have been recalled from the market due to concerns over clinical safety. These findings raise concerns over the efficacy of the 510(k) route in ensuring patient safety.

Soft tissue injuries represent a substantial and growing social and economic burden. Medical fibres are commonly used to repair these injuries during surgery. Patient's outcomes are, however, not promising with around 40% of surgical repairs failing within the first few months after surgery due to poor tissue regeneration. The application of nanofibrous filaments and yarns as medical fibres and scaffolds has been suggested to improve soft tissue regeneration and enhance the quality of the repair. However, due to a lack of robustness and reliability of the current fabrication methods, continuous nanofibrous filaments cannot be manufactured and scaled up in industrial settings and are not currently available for clinical use. We have developed a robust and automated method that enables the manufacture of continuous electrospun filaments and which has the potential to be integrated into existing textile production lines. The technology uses a wire guide to form submicrofibres in a dense, narrow mesh which can be detached as a long and continuous thread. The thread can then be stretched and used to create multifilament yarns which can imitate the hierarchical architecture of tissues such as tendons and ligaments. Electrospun polydioxanone yarns produced by this method showed improved cellular proliferation and adhesion when compared to medical monofilament fibres in current clinical use. In vivo, the electrospun yarns showed a good safety profile with mild foreign body reaction and complete degradation within 5 months after implantation. These results suggest that this filament collection method has the potential to become a useful platform for the fabrication of future medical textiles.

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 167N, 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.

Mesenchymal stem cells (MSCs) have become an area of intense interest in the treatment of musculoskeletal conditions, such as muscle and tendon injury, as various animal and human trials have demonstrated that implantation with MSCs leads to improved healing and function. However, these trials have usually been relatively small scale and lacking in adequate controls. Additionally, the optimum source of these cells has yet to be determined, partly due to a lack of understanding as to how MSCs produce their beneficial effects when implanted. Scaffolds have been shown to improve tissue-engineering repairs but require further work to optimize their interactions with both native tissue and implanted MSCs. Robust, well-controlled trials are therefore required to determine the usefulness of MSCs in musculoskeletal tissue repair.

Introduction Nanofibrous electrospun materials have been previously proposed as scaffolds for tendon repair, for their ability to mimic tendon structures and to encourage tissue regeneration. 1,2 In particular, creating filaments out of electrospun fibres offers the possibility to build larger structures with tailored morphologies and mechanical properties. In this paper, we present the potential of a new range of electrospun filaments which could be used for the repair of soft tissue such as tendon. Method Continuous polydioxanone (PDO) electrospun filaments were produced with a single nozzle electrospinning set-up using a wire-guide collector. Filaments were stretched and assembled into 4- and 16-plied yarns by twisting them with a hand spinning device. Scanning electron microscopy was used to observe the morphology of the filaments and yarns. For in vitro work, human tendon cells were extracted from rotator cuff tendon tissue obtained during surgical repair, with appropriate ethical approval. Cells were cultured on the yarns for up to 21 days and morphology was observed by fluorescence microscopy (actin-phalloidin). For mechanical testing, 6 specimens per type of yarn were tested to failure in tension using Zwick machine at rate of 0.3 mm/min. Results Stretching filaments resulted in alignment of the electrospun nanofibres along the fibre axis (Figure 1a). The twist resulting from the assembly into 4-plied yarns is observed in Figure 1b. In vitro work shows excellent attachment of human tenocytes to the nanofibrous multifilament yarns (Figure 1c). Moreover, cells are shown to align in the direction of the nanofibre orientation. As expected, the mechanical strength of the yarn is proportional to the number of filaments added (Figure 1d). Discussions While the bundles of aligned electrospun fibres closely resemble the morphology of collagen fibrils in native tendon, the assembly of the filaments into larger structures can be used to mimic tendons fascicles. In particular, native tendon fascicles have been shown to present a helix structure. 3 With their elongated shape, cells grown on these filaments also display a similar morphology to tenocytes seen in native tendons. Finally, adjusting the number of filaments can be used to tailor the mechanical strength of the yarn. With this combination of features, nanofibrous yarns hold great promises to support tendon repair. References Hakimi O, et al . eCM Journal. 2012;24:344–357 Bosworth, et al . J Mater Sci Mater Med. 2013;24:1605–1614 Thorpe. et al . J R Soc . Interface. 2014;11:20131058