Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair

Abstract

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

In Vitro Assessment of Bacterial Adhesion and Biofilm Formation on Novel Bioactive, Biodegradable Electrospun Fiber Meshes Intended to Support Tendon Rupture Repair

“…Pure DP electrospun tubes implanted around conventionally sutured rabbit Achilles tendons previously showed 20% decreased adherence of the newly formed tissue to neighboring areas 7 and we recently showed that addition of the insulin-like growth factor IGF-1 (DP-IGF-1) increased proliferation and matrix synthesis and increased mechanical superiority as compared to DP-only implants. 11 In order to further improve and decrease adhesion formation between implant and tissue, we developed two novel materials, using a blend of high molecular weight HA and PEO in a ratio of 1:1 and 1:4 (HA/PEO 1:1 and HA/ PEO 1:4, respectively), two commodity and cheap materials that are FDA approved and therefore easily translatable into the clinical setting. On the other hand, a further novel material based on pure DP treated with nAg (DP-Ag) was engineered to dampen bacterial attachment.…”

“…Three materials are based on block-co-polymer DP, either pure (DP), 7 treated with silver nanoparticles (DP-Ag) or in combination with insulin-like growth factor 1 (DP-IFG-1). 11 Two materials are based on a blend of high-molecular-weight HA and PEO in a 1:1 (HA/ PEO 1:1) or 1:4 (HA/PEO 1:4) ratio, all serving the optimization of surgical tendon repair. All materials are planned to be implanted as thin, very elastic tubes around sutured tendons.…”

“…In this study, we tested bacterial adhesions and biofilm formation on five implant materials. Three materials are based on block-co-polymer DP, either pure (DP), treated with silver nanoparticles (DP-Ag) or in combination with insulin-like growth factor 1 (DP-IFG-1) . Two materials are based on a blend of high-molecular-weight HA and PEO in a 1:1 (HA/PEO 1:1) or 1:4 (HA/PEO 1:4) ratio, all serving the optimization of surgical tendon repair.…”

“…PEG (30 wt %) was dissolved in chloroform at room temperature and used for electrospinning the next day. For emulsion electrospinning, a first solution of IGF-1, namely, 400 μL of recombinant human IGF-1 (PeproTech, #100-11-100UG, USA, 10 μg/mL IGF-1, 0.25% rabbit serum albumin as a carrier for IGF-1, in PBS) were added dropwise to a second solution of 5 g of DP dissolved in chloroform/hexafluoropropanol [CHCl 3 /HFP 80:20 (v/v)] while stirring for 5 min on the magnetic stirrer at 500 rpm and further emulsified in an ultrasonic bath for 15 min, like previously reported . The solution was used directly for electrospinning.…”

“…7 To address the problem of inferior stability, the materials can be fabricated by emulsion electrospinning allowing the incorporation of growth factors (GFs), such as the platelet-derived growth factor-BB (PDGF-BB), 8−10 a mitogenic and chemotactic GF supporting collagen synthesis, 9,10 promoting tendon healing and yielding stronger tendons, that are less prone to rerupture. In order to enhance such implant materials with respect to tendon healing support, 10 we recently developed emulsion electrospun DP fiber meshes with incorporated insulin-like growth factor-1 (DP-IGF-1), 11 known to stimulate connective tissue repair 12 and accelerate tendon healing when overexpressed. Besides fibrous adhesion formation and lower mechanical properties of the repaired tendon, bacterial infections of grafts used to bridge tendon defects 13 or implants that aid tendon healing 14 are a further serious clinical problem.…”