Effects of cross-linking molecular weights in a hyaluronic acid–poly(ethylene oxide) hydrogel network on its properties

Abstract

We examined the effects of cross-linking molecular weights on the properties of a hyaluronic acid (HA)-poly(ethylene oxide) (PEO) hydrogel. Swelling behaviors, mechanical strength and rheological behaviors of the HA-PEO hydrogel were evaluated by employing different cross-linking molecular weights (100 kDa and 1.63 mDa) of the HAs in the hydrogel networks. The low molecular weight of HA was obtained in advance by treating high molecular weight HA with a hydrogen chloride solution. Methacrylation of HA was obtained by grafting aminopropylmethacrylate to its caroboxylic acid functional groups. While reduction of the HA molecular weights was confirmed by gel permeation chromatography, the degree of methacrylate grafting to the HA was measured by (1)H-nuclear magnetic resonance. Synthesis of the HA-PEO hydrogel was successfully achieved via the Michael-type addition reaction between the methacrylate arm groups in the HA and the six thiol groups in PEO. The hydrogel formation was not dependent upon the HA molecular weights and its gelation behaviors were markedly different. Compared to the properties of the high molecular weight HA-based PEO one, the low molecular weight HA-based hydrogel induced quicker hydrogelation, as observed from the behaviors of the elastic and viscous modulus. Furthermore, the low molecular weight HA-based hydrogel demonstrated stronger mechanical properties as measured with a texture analyzer, lower water absorption as measured with a microbalance and smaller pore sizes on its surface and cross section as observed with scanning electron microscopy. The information about the effects of the cross-linking molecular weights of the gel network on the properties of the HA-based PEO hydrogel may lead to better design of hydrogels, especially in tissue engineering applications.

A Safe-by-Design Approach for the Synthesis of a Novel Cross-Linked Hyaluronic Acid with Improved Biological and Physical Properties

“…It is known that the cross-linking process leads to a reduction in the ability of the polymer to absorb water. Therefore, the behavior observed in the HA–Arg agreed with the previous literature [ 59 , 60 , 61 ].…”

Design, Synthesis, Characterization, and In Vitro Evaluation of a New Cross-Linked Hyaluronic Acid for Pharmaceutical and Cosmetic Applications

“…HA-Orn cross-linking showed a final water content value of 37.1% at 90% RH. This behavior is in accordance with the characteristics of the novel cross-linking process that leads to a reduction in the polymer's ability to absorb water [56,57].…”

Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a Supramolecular Peptide Matrix

“…One way to strengthen HA and reduce its biodegradation rate is to introduce cross-linking agents . Previous efforts included forming a physically, ionically, or covalently associated network of HA chains using various cross-linking agents, such as disulfide, divinyl sulfone, carbodiimide, polyvalent hydrazide, diamine, biotin, poly­(ethylene glycol) derivatives, and photo cross-linking by single- and two-photon tyramine oxidation. , Yet, the storage moduli of the cross-linked HA were still in the range of a few hundred Pascals. , Another technique to further strengthen cross-linked HA is in situ precipitation, in which nanoparticles are incorporated within HA . Using this technique, Kim’s group fabricated a nanocomposite HA–hydroxyapatite hydrogel as a dermal filler, exhibiting a storage modulus of 1000 Pa .…”