Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Benedict Lotz - , Heidelberg University  (Author)
  • Friederike Bothe - , Heidelberg University  (Author)
  • Anne Kathrin Deubel - , Heidelberg University  (Author)
  • Eliane Hesse - , Heidelberg University  (Author)
  • Yvonne Renz - , Heidelberg University  (Author)
  • Carsten Werner - , Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (Author)
  • Simone Schäfer - , University of Würzburg (Author)
  • Thomas Böck - , University of Würzburg (Author)
  • Jürgen Groll - , University of Würzburg (Author)
  • Brigitte Von Rechenberg - , University of Zurich (Author)
  • Wiltrud Richter - , Heidelberg University  (Author)
  • Sebastien Hagmann - , Heidelberg University  (Author)

Abstract

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

Details

Original languageEnglish
Article number5583815
JournalInternational Journal of Biomaterials
Volume2021
Publication statusPublished - 2021
Peer-reviewedYes

External IDs

ORCID /0000-0003-0189-3448/work/161890276

Keywords

ASJC Scopus subject areas