TGF–β3 Loaded Electrospun Polycaprolacton Fibre Scaffolds for Rotator Cuff Tear Repair: An in Vivo Study in Rats

Abstract

Biological factors such as TGF–β3 are possible supporters of the healing process in chronic rotator cuff tears. In the present study, electrospun chitosan coated polycaprolacton (CS–g–PCL) fibre scaffolds were loaded with TGF–β3 and their effect on tendon healing was compared biomechanically and histologically to unloaded fibre scaffolds in a chronic tendon defect rat model. The biomechanical analysis revealed that tendon–bone constructs with unloaded scaffolds had significantly lower values for maximum force compared to native tendons. Tendon-bone constructs with TGF–β3-loaded fibre scaffolds showed only slightly lower values. In histological evaluation minor differences could be observed. Both groups showed advanced fibre scaffold degradation driven partly by foreign body giant cell accumulation and high cellular numbers in the reconstructed area. Normal levels of neutrophils indicate that present mast cells mediated rather phagocytosis than inflammation. Fibrosis as sign of foreign body encapsulation and scar formation was only minorly present. In conclusion, TGF–β3-loading of electrospun PCL fibre scaffolds resulted in more robust constructs without causing significant advantages on a cellular level. A deeper investigation with special focus on macrophages and foreign body giant cells interactions is one of the major foci in further investigations.

Nanofiber Scaffolds by Electrospinning for Rotator Cuff Tissue Engineering

“…In histological evaluation, minor differences could be observed. 79 In conclusion, TGF–β3-loading of electrospun PCL fiber scaffolds resulted in more robust constructs without causing significant advantages on a cellular level. 79 …”

“… 96 97 However, the biomechanical analysis revealed that tendon–bone constructs with unloaded scaffolds had significantly lower values for maximum force compared to native tendons. 79 Tendon-bone constructs with TGF–β3-loaded fiber scaffolds showed only slightly lower values, but still were inferior to native tendons. In histological evaluation, minor differences could be observed.…”

“…Strategies have been explored for enhancing the mechanical and tendon matrix properties of electrospun scaffolds as well as restoring the enthesis of the rotator cuff by a combination of natural polymers, 24 growth factors, 79 80 or woven fiber. 81 Gelatin is a derivative of collagen obtained via controlled hydrolysis and is the major component of skin, bones, and connective tissues.…”

“…The same group further investigated the usefulness of CS-g-PCL nanofiber mats in combination of transforming growth factor beta 3 (TGF–β3) for rotator cuff healing. 79 With respect to the tendon-to-bone environment and especially to the enthesis, members of the transforming growth factor β (TGF–β) superfamily are of particular interest because these proteins are known to stimulate chondrogenic differentiation of mesenchymal stromal cells. 96 97 However, the biomechanical analysis revealed that tendon–bone constructs with unloaded scaffolds had significantly lower values for maximum force compared to native tendons.…”

“… 52 78 Even chitosan-graft-PCL coated electrospun PCL scaffolds, recently reported in rat models, 92 100 failed to achieve the Young's Modulus of intact control infraspinatus tendon (9.3±4.4 MPa in suture-fixed tendons, 13.8±5.4 MPa in the CS-g-PCL-patched group, and 20.6±10.3 MPa in intact control group). 79 Viscoelastic measurements are also not commonly used for mechanical analysis of rotator cuff scaffolds, probably due to the lack of attention to viscoelastic behavior or the thin sheet geometry (typically about tens or hundreds of µm thickness) that is insufficient for dynamic mechanical analysis testing (with the thickness of several mm). 52 With viscoelastic properties, tendons at low strain rates tend to absorb more mechanical energy but are less effective in carrying mechanical loads.…”