Effectiveness of BMP-2 and PDGF-BB Adsorption onto a Collagen/Collagen-Magnesium-Hydroxyapatite Scaffold in Weight-Bearing and Non-Weight-Bearing Osteochondral Defect Bone Repair: In Vitro, Ex Vivo and In Vivo Evaluation

Author:

Xu Jietao1ORCID,Fahmy-Garcia Shorouk12,Wesdorp Marinus A.1,Kops Nicole1,Forte Lucia3,De Luca Claudio3,Misciagna Massimiliano Maraglino3,Dolcini Laura3,Filardo Giuseppe4,Labberté Margot5,Vancíková Karin5ORCID,Kok Joeri6ORCID,van Rietbergen Bert6,Nickel Joachim7ORCID,Farrell Eric2ORCID,Brama Pieter A. J.5,van Osch Gerjo J. V. M.189ORCID

Affiliation:

1. Department of Orthopedics and Sports Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands

2. Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands

3. Fin-Ceramica Faenza S.p.A, 48018 Faenza, Italy

4. Applied and Translational Research Center, IRCCS Rizzoli Orthopaedic Institute, 40136 Bologna, Italy

5. School of Veterinary Medicine, University College Dublin, D04 V1W8 Dublin, Ireland

6. Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands

7. Department Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, 97070 Würzburg, Germany

8. Department of Otorhinolaryngology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands

9. Department of Biomechanical Engineering, Delft University of Technology, 2628 CD Delft, The Netherlands

Abstract

Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.

Funder

the European Union’s Horizon 2020 research and innovation programme

the Applied and Engineering Sciences section of the Dutch Research Council, The Netherlands (NWO-TTW), the Science Foundation of Ireland

the Ministero della Salute (IMH), Italy

Publisher

MDPI AG

Subject

Biomedical Engineering,Biomaterials

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