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

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...

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Main Authors: Benedict Lotz, Friederike Bothe, Anne-Kathrin Deubel, Eliane Hesse, Yvonne Renz, Carsten Werner, Simone Schäfer, Thomas Böck, Jürgen Groll, Brigitte von Rechenberg, Wiltrud Richter, Sebastien Hagmann
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Biomaterials
Online Access:http://dx.doi.org/10.1155/2021/5583815
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author Benedict Lotz
Friederike Bothe
Anne-Kathrin Deubel
Eliane Hesse
Yvonne Renz
Carsten Werner
Simone Schäfer
Thomas Böck
Jürgen Groll
Brigitte von Rechenberg
Wiltrud Richter
Sebastien Hagmann
author_facet Benedict Lotz
Friederike Bothe
Anne-Kathrin Deubel
Eliane Hesse
Yvonne Renz
Carsten Werner
Simone Schäfer
Thomas Böck
Jürgen Groll
Brigitte von Rechenberg
Wiltrud Richter
Sebastien Hagmann
author_sort Benedict Lotz
collection DOAJ
description 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.
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spelling doaj-art-b71c36e6eaca4cc1b1ea1b3c17c79e412025-08-20T02:23:09ZengWileyInternational Journal of Biomaterials1687-87871687-87952021-01-01202110.1155/2021/55838155583815Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal ModelBenedict Lotz0Friederike Bothe1Anne-Kathrin Deubel2Eliane Hesse3Yvonne Renz4Carsten Werner5Simone Schäfer6Thomas Böck7Jürgen Groll8Brigitte von Rechenberg9Wiltrud Richter10Sebastien Hagmann11Center of Orthopaedic and Trauma Surgery/Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyResearch Center for Experimental Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyResearch Center for Experimental Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyResearch Center for Experimental Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyResearch Center for Experimental Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyLeibniz Institute of Polymer Research Dresden, Hohe Straße 6, Dresden 01069, GermanyChair of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, Pleicherwall 2, Würzburg 97070, GermanyChair of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, Pleicherwall 2, Würzburg 97070, GermanyChair of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, Pleicherwall 2, Würzburg 97070, GermanyMusculoskeletal Research Unit (MSRU) Center for Applied Biotechnology and Molecular Medicine (CABMM), University Zürich, Winterthurerstraße 190, CH-8057 Zürich, SwitzerlandResearch Center for Experimental Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyCenter of Orthopaedic and Trauma Surgery/Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, GermanyReinforced 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.http://dx.doi.org/10.1155/2021/5583815
spellingShingle Benedict Lotz
Friederike Bothe
Anne-Kathrin Deubel
Eliane Hesse
Yvonne Renz
Carsten Werner
Simone Schäfer
Thomas Böck
Jürgen Groll
Brigitte von Rechenberg
Wiltrud Richter
Sebastien Hagmann
Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
International Journal of Biomaterials
title Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
title_full Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
title_fullStr Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
title_full_unstemmed Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
title_short Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
title_sort preclinical testing of new hydrogel materials for cartilage repair overcoming fixation issues in a large animal model
url http://dx.doi.org/10.1155/2021/5583815
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