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

Janin Reifenrath,Mathias Wellmann,Merle Kempfert,Nina Angrisani,Sarah Gniesmer,Elmar Willbold,Andreas Kampmann,Bastian Welke,Henning Menzel

doi:10.3390/ijms21031046

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.

Highlights

In recent decades, remarkable progress in different fields of medicine was achieved with respect to e.g., diagnostic tools, pharmacological and therapeutic approaches, or surgical techniques
In the CS–g–PCL group one animal was slightly lame until day nine and in the TGF–β3–CS–g–PCL group three animals showed a slight lameness until day nine and two animals until day ten
The effect of TGF–β3 loaded CS–g–PCL fibre scaffolds compared to unloaded CS–g–PCL fibre scaffolds was examined in a chronic rotator cuff tear rat model

Summary

Introduction

Remarkable progress in different fields of medicine was achieved with respect to e.g., diagnostic tools, pharmacological and therapeutic approaches, or surgical techniques. Chronic rotator cuff tears are among the most observed clinical problems of the upper extremity [2,3] These tears arise slowly and it often takes a longer time span before affected patients seek medical attention. During this time span, unfavourable pathological changes such as the retraction of the tendon, muscle atrophy, and fatty infiltration can occur [4] and these chronic degenerations lead to poor healing results in humans and in animals [5]. To approach these problems, during recent years attention has moved away from rather technical–surgical aspects, e.g., increasing the tensile strength of sutures, towards a better understanding of the biological fundamentals and the mechanical, molecular and cellular mechanisms of tendon healing and especially the biological characteristics of the enthesis and the tendon-to-bone environment [11,12,13,14]

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Conclusion