Solutions were agitated at room temperature on a roller for at least 24 h to allow for complete dissolution of the polymers. Polymer solutions were prepared by dissolving polydioxanone (PDO, 1.5–2.2 dl/g, Evonik, Essen, Germany) or polycaprolactone (PCL, Vornia, Dublin, Ireland) into 1, 1, 1, 3, 3, 3-hexafluoroisopropanol (HFIP, Apollo Scientific Limited, Cheshire, UK) at concentrations of 11% and 20% respectively (weight to volume ratios).
#Pdo meaning Patch#
The aims of this study were to investigate if a woven and electrospun PDO/PCL patch could safely induce a positive endogenous tendon fibroblast response and enable tendon repair in a non-healing large animal model.
A recently reported validated ovine model of tendon injury which does not heal spontaneously is now available, allowing improved experimental design 18. This spontaneous repair complicates evaluation of the efficacy of an augmentation strategy as the main objective is to induce a reparative cellular response. In vitro studies demonstrate that electrospun scaffolds promote mesenchymal stem cell differentiation, tendon-derived cell attachment and cellular proliferation 17. The biomimetic properties of electrospun micro- and nanoscale fibers have been shown to provide biophysical cues to a range of musculoskeletal cell types 14, 15, 16. In an attempt to address these issue we developed a synthetic biodegradable patch made of aligned electrospun fibers reinforced by a woven monofilament mesh 13. Concerns also exist about serious complications arising from nonabsorbable synthetic meshes which can erode surrounding tissues causing chronic pain, particularly when used in the pelvis. DNA has been identified in some patches, raising further serious safety concerns over the use of ECM based materials 10, 11, 12. Porcine small intestinal submucosa (SIS) patches have been shown to illicit an adverse foreign body immunological response. Concerns exist about the use of ECM based scaffolds, including the risk of disease transmission, graft rejection, and sterile inflammation. Controlled clinical studies have shown limited success in terms of healing rate and improved pain and function 8, 9. A disadvantage of many of the currently available materials is that they do not accurately mimic the ultrastructure of tendon. These patches may be made from synthetic polymers or based on modified human or animal extracellular matrix (ECM). Artificial scaffolds have also been employed in other clinical areas such as hernia repair and ligament reconstruction. Augmentation patch strategies have been proposed and are intended to provide mechanical support during repair healing and may also provide a scaffold for host tissue integration 6, 7. Unfortunately repair failure rates are high, around 40%, and can adversely affect patient outcomes 5. Rotator cuff tendon tears are the most common cause of shoulder pain in adults and patients with persistent symptoms, which often require surgical repair 3, 4. Soft tissue disorders, such as tendon disease and tears, account for a significant component of this burden 1, 2.
Musculoskeletal disorders account for around 30% of all years lived with disability globally, and this is forecast to rise by 70% by 2030. In conclusion, we demonstrate that an endogenous healing response can be safely induced in tendon by means of biophysical cues using a woven and electrospun patch. There were no local or systemic signs of excessive inflammation with normal hematology and serology for inflammatory markers three months after scaffold implantation. CD45 +, CD4 + and CD14 + cells were also present, with few foreign body giant cells. Tendon fibroblasts were the most abundant scaffold-populating cell type. The cellular infiltrate into the electrospun fibres was accompanied by an extensive network of new blood vessel formation. Significant infiltration of tendon fibroblasts was observed within the electrospun component of the patch but not within the woven component. Patches were implanted into 8 female adult English Mule sheep. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. We investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair.
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