Mechanical Integrity in a Dynamic Interpenetrating Hydrogel Network of Supramolecular Peptide-Polysaccharide Supports Enhanced Chondrogenesis.

Tissue engineering demands intelligently designed scaffolds that encompass the properties of the target tissues in terms of mechanical and bioactive properties. An ideal scaffold for engineering a cartilage tissue should provide the chondrocytes with a favorable 3D microarchitecture apart from possessing optimal mechanical characteristics such as compressibility, energy dissipation, strain stiffening, etc. Herein, we used a unique design approach to develop a hydrogel having a dynamic interpenetrating network to serve as a framework to support chondrocyte growth and differentiation. An amyloid-inspired peptide amphiphile (1) was self-assembled to furnish kinetically controlled nanofibers and incorporated in a dynamic covalently cross-linked polysaccharide network of carboxymethyl cellulose dialdehyde (CMC-D) and carboxymethyl chitosan (CMCh) using Schiff base chemistry. The dynamic noncovalent interaction played a pivotal role in providing the desired modulation in the structure and mechanical properties of the double-network hydrogels that are imperative for cartilage scaffold design. The adaptable nature supported shear-induced extrusion of the hydrogel and facilitated various cellular functions while maintaining its integrity. The potential of the as-developed hydrogels to support in vitro chondrogenesis was explored using human chondrocytes. Evidence of improved cell growth and cartilage-specific ECM production confirmed the potential of the hydrogel to support cartilage tissue engineering while reaffirming the significance of mimicking the biophysical microenvironment to induce optimal tissue regeneration.