title: Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based Doubly Cross-Linked Networks.
abstract: We have created a new class of hyaluronic acid (HA)-based hydrogel materials with HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a secondary network. HA HGPs with an average diameter of ∼900 nm and narrow particle size distribution were synthesized using a refined reverse micelle polymerization technique. The average mesh size of the HGPs was estimated to be approximately 5.5 to 7.0 nm by a protein uptake experiment. Sodium periodate oxidation not only introduced aldehyde groups to the particles but also reduced the average particle size. The aldehyde groups generated were used as reactive handles for subsequent cross-linking with an HA derivative containing hydrazide groups. The resulting macroscopic gels contain two distinct hierarchical networks (doubly cross-linked networks, DXNs): one within individual particles and another among different particles. Bulk gels (BGs) formed by direct mixing of HA derivatives with mutually reactive groups were included for comparison. The hydrogel microstructures were collectively characterized by microscopy and neutron scattering techniques. Their viscoelasticity was quantified at low frequencies (0.1-10 Hz) using a controlled stress rheometer and at high frequencies (up to 200 Hz) with a home-built torsional wave apparatus. Both BGs and DXNs are stable elastic gels that become stiffer at higher frequencies. The HA-based DXN offers unique structural hierarchy and mechanical properties that are suitable for soft tissue regeneration.
authors.affiliation: Departments of Materials Science and Engineering, Biological Sciences, and Mechanical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19716, and Division of Engineering, Box D, Brown University, Providence, Rhode Island 02912.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Jha
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Hule
authors.forename: Tong
authors.initials: T
authors.lastname: Jiao
authors.forename: Sean S
authors.initials: SS
authors.lastname: Teller
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Clifton
authors.forename: Randall L
authors.initials: RL
authors.lastname: Duncan
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia