Article ID Journal Published Year Pages File Type
5201590 Polymer Degradation and Stability 2015 11 Pages PDF
Abstract

This paper examines the reversible enamine crosslinking reaction between poly-l-lysine (PLL) and poly (methacrylic acid-co-2[methacryloyloxy]ethyl acetoacetate) (70:30 mol%, A70), used to form crosslinked networks for cell encapsulation. Comparison of polymeric and small-molecule reactants showed that the equilibrium formation of enamine from amine and acetoacetate in water [0.02 M each] increased from 1 to 12 mol% upon going from small molecules to a polymer (A70) - oligomer (oligoPLL, 1-5 kDa) model. This increase is attributed to higher local reactant concentration and the formation of a hydrophobic microenvironment, both the result of polyelectrolyte complexation.While enamine formation reached equilibrium levels within hours, storage of both enamine-functional linear polymers, and enamine-crosslinked network polymers, in aqueous media at 40 °C led to loss of enamine with an apparent half-life of about two weeks. This slow loss of enamine is attributed to hydrolysis of acetoacetate ester linkages in the A70, which causes a corresponding decrease of the polymer-bound acetoacetates available to participate in the equilibrium crosslinking reaction.Accordingly, calcium alginate capsules reinforced with an enamine-crosslinked A70/PLL network lost their covalent reinforcement after storage under physiological conditions for several weeks. Breakdown occurred after two weeks for a covalent network made with low MW PLL (1-5 kDa) while one made with higher MW PLL (15-30 kDa) was still intact after one month. This loss of enamine crosslinks driven by hydrolysis of the acetoacetate component leads to a mechanism for decrosslinking covalent A70-PLL networks on a timescale that would allow encapsulated cells to generate their own extracellular matrix.

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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