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Development of collagen-poly(caprolactone)-based core-shell scaffolds supplemented with proteoglycans and glycosaminoglycans for ligament repair

journal contribution
posted on 17.06.2021, 14:22 by Pedro Jose Gouveia, Tom HodgkinsonTom Hodgkinson, Isabel Mauricio AmadoIsabel Mauricio Amado, Joanna SadowskaJoanna Sadowska, Alan Ryan, Sara Romanazzo, Simon Carroll, Sally-Ann CryanSally-Ann Cryan, Daniel J. Kelly, Fergal O'BrienFergal O'Brien
Core-shell scaffolds offer a promising regenerative solution to debilitating injuries to anterior cruciate ligament (ACL) thanks to a unique biphasic structure. Nevertheless, current core-shell designs are impaired by an imbalance between permeability, biochemical and mechanical cues. This study aimed to address this issue by creating a porous core-shell construct which favors cell infiltration and matrix production, while providing mechanical stability at the site of injury. The developed core-shell scaffold combines an outer shell of electrospun poly(caprolactone) fibers with a freeze-dried core of type I collagen doped with proteoglycans (biglycan, decorin) or glycosaminoglycans (chondroitin sulphate, dermatan sulphate). The aligned fibrous shell achieved an elastic modulus akin of the human ACL, while the porous collagen core is permeable to human mesenchymal stem cell (hMSC). Doping of the core with the aforementioned biomolecules led to structural and mechanical changes in the pore network. Assessment of cellular metabolic activity and scaffold contraction shows that hMSCs actively remodel the matrix at different degrees, depending on the core's doping formulation. Additionally, immunohistochemical staining and mRNA transcript levels show that the collagen-chondroitin sulphate formulation has the highest matrix production activity, while the collagen-decorin formulation featured a matrix production profile more characteristic of the undamaged tissue. Together, this demonstrates that scaffold doping with target biomolecules leads to distinct levels of cell-mediated matrix remodeling. Overall, this work resulted in the development of a versatile and robust platform with a combination of mechanical and biochemical features that have a significant potential in promoting the repair process of ACL tissue.

Funding

Science Foundation Ireland AMBER Centre (SFI/12/RC/2278 and SFI/12/ RC/2278_P2; Ireland)

European Research Council under the European Community’s Horizon 2020 research and innovation programme (Advanced Grant agreement n◦ 788753, "ReCaP"; Ireland)

Science Foundation Ireland under the US-Ireland Research and Development Partnership (grant 17/ US/3437; Ireland)

History

Comments

The original article is available at https://www.sciencedirect.com

Published Citation

Gouveia PJ, Hodgkinson T, Amado I, Sadowska JM, Ryan AJ, Romanazzo S, Carroll S, Cryan SA, Kelly DJ, O'Brien FJ. Development of collagen-poly(caprolactone)-based core-shell scaffolds supplemented with proteoglycans and glycosaminoglycans for ligament repair. Mater Sci Eng C Mater Biol Appl. 2021;120:111657.

Publication Date

20 October 2020

PubMed ID

33545824

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • RCSI Tissue Engineering Group (TERG)
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

Elsevier

Version

  • Accepted Version (Postprint)