Neutral, water-soluble poly(ester amide) hydrogels for cell encapsulation

Abstract

Hydrogels are of significant interest for cell encapsulation and delivery in regenerative medicine. Poly(ester amide)s (PEAs) are a class of biodegradable polymers that exhibit promise for biomedical applications due to the degradability of the ester and amide linkages in their backbones, their preparation from biomolecules such as amino acids, and the ability to readily tune their properties through a modular synthesis approach. Water-soluble PEAs containing cationic arginine moieties have previously been developed, but to the best of our knowledge, neutral water-soluble PEAs based on non-charged amino acids have not been reported. Using a poly(ethylene glycol) (PEG)-based macromonomer, we describe here the syntheses of water-soluble amino acid-containing PEAs containing crosslinkable alkenes in their backbones. These PEAs were converted into hydrogels through photoinitiated crosslinking and their properties were compared, including gel content, water content, swelling, and Young’s moduli. Subsequent cell culture studies on a subset of hydrogels confirmed that human adipose-derived stromal cells (ASCs) showed > 75% viability at 24 h post-encapsulation. To explore the potential of the hydrogels as cell delivery systems for applications in soft tissue regeneration, adipogenic differentiation of the encapsulated ASCs was probed in vitro at 7 days. Analysis of glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity and intracellular lipid accumulation indicated that the hydrogels provided a supportive environment for ASC adipogenesis. Overall, these PEAs provide a new platform that warrants further development for regenerative medicine applications.