TY - JOUR
T1 - Bi-layered micro-fibre reinforced hydrogels for articular cartilage regeneration
AU - Castilho, Miguel
AU - Mouser, Vivian
AU - Chen, Mike
AU - Malda, Jos
AU - Ito, Keita
N1 - Funding Information:
The authors gratefully thank the strategic alliance University Medical Center Utrecht – Eindhoven University of Technology and the European Research Council (ERC) consolidator grant 3D-JOINT (#6474426) for their financial support. In addition, the authors are very grateful to Inge Dokter for all the support with the cell harvesting, in vitro culture and characterization; to Sylvia van Kogelenber and to Joost H van Duijn for their technical support with the fibre scaffold design and 3D printing process; and finally, to Jurgen Bulsink for the support with the bioreactor system design.
Publisher Copyright:
© 2019 Acta Materialia Inc.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Articular cartilage has limited capacity for regeneration and when damaged cannot be repaired with currently available metallic or synthetic implants. We aim to bioengineer a microfibre-reinforced hydrogel that can capture the zonal depth-dependent mechanical properties of native cartilage, and simultaneously support neo-cartilage formation. With this goal, a sophisticated bi-layered microfibre architecture, combining a densely distributed crossed fibre mat (superficial tangential zone, STZ) and a uniform box structure (middle and deep zone, MDZ), was successfully manufactured via melt electrospinning and combined with a gelatin-methacrylamide hydrogel. The inclusion of a thin STZ layer greatly increased the composite construct's peak modulus under both incongruent (3.2-fold) and congruent (2.1-fold) loading, as compared to hydrogels reinforced with only a uniform MDZ structure. Notably, the stress relaxation response of the bi-layered composite construct was comparable to the tested native cartilage tissue. Furthermore, similar production of sulphated glycosaminoglycans and collagen II was observed for the novel composite constructs cultured under mechanical conditioning w/o TGF-ß1 supplementation and in static conditions w/TGF-ß1 supplementation, which confirmed the capability of the novel composite construct to support neo-cartilage formation upon mechanical stimulation. To conclude, these results are an important step towards the design and manufacture of biomechanically competent implants for cartilage regeneration. STATEMENT OF SIGNIFICANCE: Damage to articular cartilage results in severe pain and joint disfunction that cannot be treated with currently available implants. This study presents a sophisticated bioengineered bi-layered fibre reinforced cell-laden hydrogel that can approximate the functional mechanical properties of native cartilage. For the first time, the importance of incorporating a viable superficial tangential zone (STZ) - like structure to improve the load-bearing properties of bioengineered constructs, particularly when in-congruent surfaces are compressed, is demonstrated. The present work also provides new insights for the development of implants that are able to promote and guide new cartilaginous tissue formation upon physiologically relevant mechanical stimulation.
AB - Articular cartilage has limited capacity for regeneration and when damaged cannot be repaired with currently available metallic or synthetic implants. We aim to bioengineer a microfibre-reinforced hydrogel that can capture the zonal depth-dependent mechanical properties of native cartilage, and simultaneously support neo-cartilage formation. With this goal, a sophisticated bi-layered microfibre architecture, combining a densely distributed crossed fibre mat (superficial tangential zone, STZ) and a uniform box structure (middle and deep zone, MDZ), was successfully manufactured via melt electrospinning and combined with a gelatin-methacrylamide hydrogel. The inclusion of a thin STZ layer greatly increased the composite construct's peak modulus under both incongruent (3.2-fold) and congruent (2.1-fold) loading, as compared to hydrogels reinforced with only a uniform MDZ structure. Notably, the stress relaxation response of the bi-layered composite construct was comparable to the tested native cartilage tissue. Furthermore, similar production of sulphated glycosaminoglycans and collagen II was observed for the novel composite constructs cultured under mechanical conditioning w/o TGF-ß1 supplementation and in static conditions w/TGF-ß1 supplementation, which confirmed the capability of the novel composite construct to support neo-cartilage formation upon mechanical stimulation. To conclude, these results are an important step towards the design and manufacture of biomechanically competent implants for cartilage regeneration. STATEMENT OF SIGNIFICANCE: Damage to articular cartilage results in severe pain and joint disfunction that cannot be treated with currently available implants. This study presents a sophisticated bioengineered bi-layered fibre reinforced cell-laden hydrogel that can approximate the functional mechanical properties of native cartilage. For the first time, the importance of incorporating a viable superficial tangential zone (STZ) - like structure to improve the load-bearing properties of bioengineered constructs, particularly when in-congruent surfaces are compressed, is demonstrated. The present work also provides new insights for the development of implants that are able to promote and guide new cartilaginous tissue formation upon physiologically relevant mechanical stimulation.
KW - Cartilage regeneration
KW - Fibre-reinforced hydrogels
KW - Melt electrowriting
KW - Osteoarthritis
KW - Superficial tangential zone
UR - http://www.scopus.com/inward/record.url?scp=85068231041&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2019.06.030
DO - 10.1016/j.actbio.2019.06.030
M3 - Article
C2 - 31233890
SN - 1742-7061
VL - 95
SP - 297
EP - 306
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -