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Biofabrication of human articular cartilage: a path towards the development of a clinical treatment

Journal Article


Abstract


  • Cartilage injuries cause pain and loss of function, and if severe may result in osteoarthritis (OA). 3D

    bioprinting is now a tangible option for the delivery of bioscaffolds capable of regenerating the

    deficient cartilage tissue. Our team has developed a handheld device, the Biopen, to allow in situ

    additive manufacturing during surgery. Given its ability to extrude in a core/shell manner, the Biopen

    can preserve cell viability during the biofabrication process, and it is currently the only biofabrication

    tool tested as a surgical instrument in a sheep model using homologous stem cells. As a necessary step

    toward the development of a clinically relevant protocol, we aimed to demonstrate that our handheld

    extrusion device can successfully be used for the biofabrication of human cartilage. Therefore, this

    study is a required step for the development of a surgical treatment in human patients. In this work we

    specifically used human adipose derived mesenchymal stem cells (hADSCs), harvested from the infrapatellar

    fat pad of donor patients affected by OA, to also prove that they can be utilized as the source of

    cells for the future clinical application. With the Biopen, we generated bioscaffolds made of hADSCs

    laden in gelatin methacrylate, hyaluronic acid methacrylate and cultured in the presence of

    chondrogenic stimuli for eight weeks in vitro. A comprehensive characterisation including gene and

    protein expression analyses, immunohistology, confocal microscopy, second harmonic generation,

    light sheet imaging, atomic force mycroscopy and mechanical unconfined compression demonstrated

    that our strategy resulted in human hyaline-like cartilage formation. Our in situ biofabrication

    approach represents an innovation with important implications for customizing cartilage repair in

    patients with cartilage injuries and OA.

Authors


  •   Onofrillo, Carmine (external author)
  •   Duchi, Serena (external author)
  •   O'Connell, Cathal (external author)
  •   Blanchard, Romane (external author)
  •   Scott, Mark (external author)
  •   O'Connor, Andrea (external author)
  •   Wallace, Gordon G.
  •   Choong, Peter (external author)
  •   Di Bella, Claudia (external author)

Publication Date


  • 2018

Citation


  • Onofrillo, C., Duchi, S., O'Connell, C. D., Blanchard, R., Scott, M., O'Connor, A. J., Wallace, G. G., Choong, P. F. M. & Di Bella, C. (2018). Biofabrication of human articular cartilage: a path towards the development of a clinical treatment. Biofabrication, 10 (4), 045006-1-045006-19.

Ro Metadata Url


  • http://ro.uow.edu.au/aiimpapers/3223

Start Page


  • 045006-1

End Page


  • 045006-19

Volume


  • 10

Issue


  • 4

Place Of Publication


  • United Kingdom

Abstract


  • Cartilage injuries cause pain and loss of function, and if severe may result in osteoarthritis (OA). 3D

    bioprinting is now a tangible option for the delivery of bioscaffolds capable of regenerating the

    deficient cartilage tissue. Our team has developed a handheld device, the Biopen, to allow in situ

    additive manufacturing during surgery. Given its ability to extrude in a core/shell manner, the Biopen

    can preserve cell viability during the biofabrication process, and it is currently the only biofabrication

    tool tested as a surgical instrument in a sheep model using homologous stem cells. As a necessary step

    toward the development of a clinically relevant protocol, we aimed to demonstrate that our handheld

    extrusion device can successfully be used for the biofabrication of human cartilage. Therefore, this

    study is a required step for the development of a surgical treatment in human patients. In this work we

    specifically used human adipose derived mesenchymal stem cells (hADSCs), harvested from the infrapatellar

    fat pad of donor patients affected by OA, to also prove that they can be utilized as the source of

    cells for the future clinical application. With the Biopen, we generated bioscaffolds made of hADSCs

    laden in gelatin methacrylate, hyaluronic acid methacrylate and cultured in the presence of

    chondrogenic stimuli for eight weeks in vitro. A comprehensive characterisation including gene and

    protein expression analyses, immunohistology, confocal microscopy, second harmonic generation,

    light sheet imaging, atomic force mycroscopy and mechanical unconfined compression demonstrated

    that our strategy resulted in human hyaline-like cartilage formation. Our in situ biofabrication

    approach represents an innovation with important implications for customizing cartilage repair in

    patients with cartilage injuries and OA.

Authors


  •   Onofrillo, Carmine (external author)
  •   Duchi, Serena (external author)
  •   O'Connell, Cathal (external author)
  •   Blanchard, Romane (external author)
  •   Scott, Mark (external author)
  •   O'Connor, Andrea (external author)
  •   Wallace, Gordon G.
  •   Choong, Peter (external author)
  •   Di Bella, Claudia (external author)

Publication Date


  • 2018

Citation


  • Onofrillo, C., Duchi, S., O'Connell, C. D., Blanchard, R., Scott, M., O'Connor, A. J., Wallace, G. G., Choong, P. F. M. & Di Bella, C. (2018). Biofabrication of human articular cartilage: a path towards the development of a clinical treatment. Biofabrication, 10 (4), 045006-1-045006-19.

Ro Metadata Url


  • http://ro.uow.edu.au/aiimpapers/3223

Start Page


  • 045006-1

End Page


  • 045006-19

Volume


  • 10

Issue


  • 4

Place Of Publication


  • United Kingdom