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Photo-crosslinked water-soluble PEA-based hydrogels for cell encapsulation: A rheological study
1, 2 , * 3 , 3 , 1, 2 , * 1, 2
1  Department of Chemical Engineering, Barcelona School of Engineering East (EEBE), Polytechnic University of Catalonia – Barcelona Tech (UPC), Av. Eduard Maristany, 10-14, Barcelona 08019, Spain
2  Barcelona Research Center for Multiscale Science and Engineering, Polytechnic University of Catalonia, Barcelona Tech (UPC), Av. Eduard Maristany, 16, Barcelona 08019, Spain
3  Le Mans Institute of Molecules and Materials (IMMM - UMR CNRS 6283), Le Mans University, Avenue Olivier Messiaen, 72085 LE MANS Cedex 9, France
Academic Editor: Dirk Kuckling

Abstract:

Introduction
Scaffolds for tissue regeneration can be made from bio-based polymers, which offer inherent biological compatibility. However, batch-to-batch variability and limited tunability restrict their broader application. In contrast, biodegradable synthetic polymers allow precise control over chemical and mechanical properties but lack biological signaling [1]. Amino acid-containing polyester amides (PEAs) address this gap by combining biocompatibility with tunability. The polyester segment ensures biodegradability, while the polyamide segment enhances mechanical and thermal stability [2]. Hydrogels based on amino acid-derived PEAs offer a favorable environment for cell proliferation, with reproducible physical and chemical properties [3–5]. Photopolymerization enables simple, non-toxic in situ gelation at physiological pH and temperature [6]. However, excessive UV exposure can damage cells [7], making it essential to minimize exposure while ensuring proper gelation.

Methods
PEAs were synthesized in two steps. First, Monomer 1 was prepared by esterifying an amino acid (L-alanine, L-valine, or L-leucine) with a diol (1,6-hexanediol, 1,10-decanediol, or 1,12-dodecanediol). Second, Monomer 1 was polymerized with di-ρ-nitrophenyl fumarate (to introduce crosslinkable sites) and PEG-diamine (for water solubility) in dimethylacetamide at 70 °C for six hours. The resulting PEAs were photo crosslinked using Irgacure 2959 or LAP. Gelation time and plateau modulus were determined by a rheological analysis of storage (G′) and loss (G″) moduli.

Results
For PEA10A5K (alanine, 1,10-decanediol), gelation times with 0.4% Irgacure, 0.5% LAP, and 0.05% LAP were 1.5 h, 3 min, and 12 min, respectively (Figure 1a). A 0.05% LAP concentration was selected for all further experiments, balancing low cytotoxicity and short gelation time. G′ correlated with polymer molecular weight rather than amino acid type (Figure 1b).

Conclusions
Gelation times were determined while keeping the minimal photoinitiator concentration, which is ideal for cell survival in the final application. Next, cell viability and encapsulation studies will be performed.

Keywords: hydrogel; photocrosslinking; gelification-kinetics; polyester amides
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