Exploring the Mechanical and Chemical Properties of Cross-Linked Poly(allylamine)-hyaluronic Acid Multilayer Films Using a Chemometric Unmixing Approach

For several decades now, modulating and controlling the mechanical properties of hydrogels, and in particular exponentially growing polyelectrolyte multilayer films (PEMs), have been a major challenge, given their importance in a wide range of applications, including tissue engineering, implantable biomaterials, and drug delivery systems. In this work, we compared the cross-linking reaction of hydrogels based on the association of poly(allylamine) (PAH) and hyaluronic acid (HA) with either 1,4-butanediol diglycidyl ether (BDDE) or divinyl sulfone (DVS) at different concentrations. On the basis of infrared data analysis by means of a chemometric method, we demonstrated that the cross-linking reaction led to significant changes in their chemical features. We deciphered how the affinity of each cross-linker to alcohol and amino chemical functions drives the chemical features of the PEMs. These features can be described by a linear combination of pure HA-BDDE, PAH-BDDE or HA-DVS, and PAH-DVS-based hydrogels with ratios of 80 and 16% for the BDDE and 55 and 45% for the DVS reactions, respectively. Furthermore, the mechanical properties resulting from the BDDE cross-linking reaction were consistent with a high mechanical contribution of HA-BDDE, as estimated by the chemometric analysis. However, this linear combination cannot be applied for DVS. Indeed, the cross-linked PEM was softer than expected, regarding the chemical contributions of HA-DVS and PAH-DVS. Our results show that it is possible to control the mechanical and chemical features by the choice of the cross-linkers alone or in a mixture.