Improving Tendon Healing with Electrospun Implants Containing Hyaluronic Acid

Abstract

Tendon is a dense viscoelastic, fibrous connective tissue that connects muscles to bones and transfers tensile loads enabling joint motion and passive joint stabilization. Due to the exposition to large mechanical loads, tendons are often affected by injuries and are responsible for about 30 % of musculoskeletal complaints. Tendons consist mainly of tightly packed, parallel-orientated collagen fibers, are hypovascular and hypocellular with a low metabolic activity and a limited natural healing capacity in consequence. In the clinics, surgery, pharmacological treatment and rehabilitation are still the gold standard so far; but re-rupture, joint stiffness and adhesion formation are common clinical problems often leading to secondary surgeries and to persistent functional disability in patient daily lives. Therefore, intensive research is being carried out to better understand the healing process and develop new treatment options. In the presented thesis, a rabbit full laceration Achilles tendon (AT) model was used to study the anti-adhesive effect of a novel implant produced by electrospinning. We aimed to improve the reported anti-adhesive effect of a biodegradable DegraPol® (DP) implant by adding an additional layer of hyaluronic acid/polyethylene oxide (HA/PEO). Hyaluronic acid (HA) is found in almost every tissue in vertebrates and is an important lubricant in the synovial fluid. Moreover, treatment of tendons with HA has shown promising results as scar formation, adhesion and gliding resistance could be reduced after surgery. As implant degradation will release HA in vivo, effect of HA on rabbit tenocytes was first investigated in vitro, before HA-containing implants were applied in the rabbit model. In vitro results have shown that such implants will not provoke a fibrotic reaction, but rather prevent adhesion formation as HA decreased matrix marker genes, downregulated the fibrosis marker  SMA and slightly increased the matrix remodeling gene MMP-2. As a HA/PEO layer was the first time combined with a pure DP layer in electrospun implants, material properties were analyzed with Scanning Electron Microscopy, Fourier-transform Infrared Spectroscopy, Differential Scanning Calorimetry, Water Contact Angle measurements, and by testing the mechanical properties. Additionally, the adherence and proliferation capacity of four clinically relevant bacterial strains on the new material have been tested because bacterial infection of implants is a severe clinical problem. Finally, the new HA/PEO-containing DP implant was used in the rabbit AT model and following histological analysis has demonstrated that adhesion extent was reduced significantly by approximately 50 % compared to a pure DP implant, reaching a level comparable to healthy tendons. Therefore, these novel bi-layered implants show great potential for a clinical application in the future.