Fully amino acid-based hydrogel as potential scaffold for cell culturing and drug delivery

Beilstein J Nanotechnol. 2019 Dec 27:10:2579-2593. doi: 10.3762/bjnano.10.249. eCollection 2019.

Abstract

Polymer hydrogels are ideal scaffolds for both tissue engineering and drug delivery. A great advantage of poly(amino acid)-based hydrogels is their high similarity to natural proteins. However, their expensive and complicated synthesis often limits their application. The use of poly(aspartic acid) (PASP) seems an appropriate solution for this problem due to the relatively cheap and simple synthesis of PASP. Using amino acids not only as building blocks in the polymer backbone but also as cross-linkers can improve the biocompatibility and the biodegradability of the hydrogel. In this paper, PASP cross-linked with cystamine (CYS) and lysine-methylester (LYS) was introduced as fully amino acid-based polymer hydrogel. Gels were synthesized employing six different ratios of CYS and LYS. The pH dependent swelling degree and the concentration of the elastically active chain were determined. After reduction of the disulfide bonds of CYS, the presence of thiol side groups was also detected. To determine the concentration of the reactive cross-linkers in the hydrogels, a new method based on the examination of the swelling behavior was established. Using metoprolol as a model drug, cell proliferation and drug release kinetics were studied at different LYS contents and in the presence of thiol groups. The optimal ratio of cross-linkers for the proliferation of periodontal ligament cells was found to be 60-80% LYS and 20-40% CYS. The reductive conditions resulted in an increased drug release due to the cleavage of disulfide bridges in the hydrogels. Consequently, these hydrogels provide new possibilities in the fields of both tissue engineering and controlled drug delivery.

Keywords: biocompatibility; cystamine; hydrogel; lysine; poly(amino acid); poly(aspartic acid); polymer.

Grants and funding

This study was supported by the Hungarian Human Resources Development Operational Program (EFOP-3.6.2-16-2017-00006). Additional support was received from the Excellence Program of the Ministry for Innovation and Technology in Hungary within the framework of the therapy thematic program of the Semmelweis University. This work was funded by the National Research, Development and Innovation Office – NKFIH FK 124147, the OTKA 115259, the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and by the ÚNKP-19-4-SE-04 new national excellence program of the Ministry for Innovation and Technology.