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

Abstract

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.

Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications

“…They introduced this hydrogel scaffold as a promising candidate for endodontic tissue engineering. Thomas et al developed a hydrogel possessing a dynamic interpenetrating network suitable for supporting chondrocyte growth and differentiation [ 145 ]. For this purpose, they used an amyloid-inspired peptide amphiphile self-assembled into nanofibers and embedded in a chemically cross-linked polysaccharide network of carboxymethyl cellulose dialdehyde (CMC-D) and carboxymethyl chitosan (CMCh).…”

Peptide Biomaterials for Tissue Regeneration

“…On the other hand, Tomas et al developed an amyloidinspired PA self-assembled to furnish kinetically controlled nanofibers and incorporated in a dynamic covalently crosslinked polysaccharide network of carboxymethyl cellulose dialdehyde and carboxymethyl chitosan (CMCh) using Schiff base chemistry, where the non-covalent interaction provided the mechanical properties to the hydrogel developed for its application in chondrogenesis, where an improved cell growth for the in vitro testing was demonstrated (Thomas et al, 2021).…”

Constructing ECM-like Structure on the Plasma Membrane via Peptide Assembly to Regulate the Cellular Response

“…Representative polymers are poly­(ethylene glycol) (PEG), , polylactic acid (PLA), , polyglutamic acid (PGA), , and poly­(ethylene oxide) (PEO). , One of the significant advantages of synthetic ECM mimics is the precise controllability and readily tunable mechanical properties. Double-network hydrogels possessing high mechanical strength and toughness have drawn increasing attention as biological tissue mimics. − Synthetic polymers usually lack supporting cues for cell contacts. This issue could be addressed by conjugating polymer-bioactive molecule hybrids. − Polymers that are functionalized with bioactive molecules such as cell-adhesive peptides, growth factors, and glycans can achieve the ability to communicate with cells and provide biochemical signals.…”