First-principles based approaches to nano-mechanical and biomimetic characterization of polymer-based hydrogel networks for cartilage scaffold-supported therapies

Atomistic-level molecular dynamics (MD) is used to investigate the thermodynamical and mechanical properties of candidate polymer-based hydrogel networks for tissue scaffold-support therapies that serve a predominantly biomechanical function, in particular articular cartilage. The MD uses force field parameters based on quantum mechanical calculations (including atomic charges and torsional potential energy curves). We provide first principles estimates of the entropic and enthalpic contributions to elastic response, cohesive energies, viscosities, and stress-strain characteristics for relevant single and double network hydrogel compositions of poly(acrylamide)-PAAm and poly(2- acrylamido-2-methylpropanesulfonic acid)-PAMPS, aimed at the functional bio-engineering of artificial tissue with high dynamic load requirements (>10's of MPa even at >90 wt-% water contents). Our results indicate the existence of covalent cross-linking mechanisms taking place during the synthesis of interpenetrating double network hydrogels at critical crosslink concentrations and as a function of starter monomer concentrations and degree of polymerization. Furthermore, percolation thresholds estimated from single chain statistics of acrylamide polymers are consistent with experimentally measured gel points and help explain the precipitous loss of the high fracture energy in double network hydrogels at low crosslink densities; favoring this mechanism, over others presented in the literature (e.g., entanglement, hydrogen bonding), as the origin of enhanced toughness for interpenetrating double network hydrogels. These findings are useful for steering experimental efforts towards systematic optimization of the bio-mimetic response of polymer-based scaffolds for tissue engineering.