1. Academic Validation
  2. RGDSP functionalized carboxylated agarose as extrudable carriers for chondrocyte delivery

RGDSP functionalized carboxylated agarose as extrudable carriers for chondrocyte delivery

  • Mater Sci Eng C Mater Biol Appl. 2019 Jun:99:103-111. doi: 10.1016/j.msec.2019.01.080.
Neha Arya 1 Aurelien Forget 2 Melika Sarem 3 V Prasad Shastri 4
Affiliations

Affiliations

  • 1 Institute for Macromolecular Chemistry, University of Freiburg, 79104 Freiburg, Germany; Helmholtz Virtual Institute on Multifunctional Biomaterials for Medicine, Kantstr. 55, 14513 Teltow, Germany.
  • 2 Institute for Macromolecular Chemistry, University of Freiburg, 79104 Freiburg, Germany.
  • 3 Institute for Macromolecular Chemistry, University of Freiburg, 79104 Freiburg, Germany; Helmholtz Virtual Institute on Multifunctional Biomaterials for Medicine, Kantstr. 55, 14513 Teltow, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
  • 4 Institute for Macromolecular Chemistry, University of Freiburg, 79104 Freiburg, Germany; Helmholtz Virtual Institute on Multifunctional Biomaterials for Medicine, Kantstr. 55, 14513 Teltow, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: [email protected].
Abstract

The limited potential of cartilage to regenerate itself has led to development of new strategies and biomaterials for cartilage tissue engineering and regenerative medicine. Although de novo strategies for cartilage repair have been realized, extrudable hydrogels that can be administered in minimally invasive manner while simultaneously supporting chondrogenic differentiation could lead to development of new systems to deliver cells to cartilage lesions. In this work, we explored the suitability of thermo-reversible, extrudable gels derived from carboxylated Agarose for maintaining human articular chondrocyte (HAC) phenotype. Towards this objective, we have investigated the impact of hydrogel stiffness and presence of integrin-binding peptide sequence GGGGRGDSP on HAC differentiation potential. We discovered that stiffer hydrogels (5.8 kPa) are more efficient than softer counterparts (0.6 kPa) in promoting chondrogenesis. Interestingly, in GGGGRGDSP modified gels, a synergy between stiffness and RGD signaling led to enhanced expression of chondrogenic related genes (aggrecan, collagen type II and sox9). These findings were also supported by quantitative analysis of sulfated glycosaminoglycans. Since carboxylated Agarose are highly suitable as bioink for 3D bioprinting, we propose that extrudable GGGGRGDSP-linked stiff carboxylated Agarose as a medium for direct printing of chondrocyte into cartilage lesion.

Keywords

3D printing; Cartilage tissue engineering; Hydrogel stiffness; Mechanical properties; Polymer extrusion.

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