Promoting endogenous articular cartilage regeneration using extracellular matrix scaffolds

David C Browe; Ross Burdis; Pedro J Díaz-Payno; Fiona E Freeman; Jessica M Nulty; Conor T Buckley; Pieter A J Brama; Daniel J Kelly

doi:10.1016/j.mtbio.2022.100343

Promoting endogenous articular cartilage regeneration using extracellular matrix scaffolds

Mater Today Bio. 2022 Jul 5:16:100343. doi: 10.1016/j.mtbio.2022.100343. eCollection 2022 Dec.

Authors

David C Browe^{1

2

3}, Ross Burdis^{1

2}, Pedro J Díaz-Payno^{1

2}, Fiona E Freeman^{1

2

4

5}, Jessica M Nulty^{1

2}, Conor T Buckley^{1

2

3

6}, Pieter A J Brama⁷, Daniel J Kelly^{1

2

3

6}

Affiliations

¹ Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
² Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland.
³ Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Ireland.
⁴ Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge, MA, 02142, USA.
⁵ Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115, USA.
⁶ Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
⁷ Section of Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Ireland.

Abstract

Articular cartilage defects fail to heal spontaneously, typically progressing to osteoarthritis. Bone marrow stimulation techniques such as microfracture (MFX) are the current surgical standard of care; however MFX typically produces an inferior fibro-cartilaginous tissue which provides only temporary symptomatic relief. Here we implanted solubilised articular cartilage extracellular matrix (ECM) derived scaffolds into critically sized chondral defects in goats, securely anchoring these implants to the joint surface using a 3D-printed fixation device that overcame the need for sutures or glues. In vitro these ECM scaffolds were found to be inherently chondro-inductive, while in vivo they promoted superior articular cartilage regeneration compared to microfracture. In an attempt to further improve the quality of repair, we loaded these scaffolds with a known chemotactic factor, transforming growth factor (TGF)-β3. In vivo such TGF-β3 loaded scaffolds promoted superior articular cartilage regeneration. This study demonstrates that ECM derived biomaterials, either alone and particularly when combined with exogenous growth factors, can successfully treat articular cartilage defects in a clinically relevant large animal model.

Keywords: Cartilage repair; ECM scaffold; Fixation device; Large animal model; Microfracture.