(287m) Characterization of Rheological Properties and Microstructure of Thioester Networks during Degradation

Covalent adaptable networks (CANs) are polymeric networks with cross-links that can be rearranged by external stimuli, such as pH, shear or external chemical stimuli. CANs are being designed for applications including as cell and drug delivery vehicles and as dissolvable wound sealants. To inform design of these evolving networks for use in these applications, it is necessary to characterize CAN degradation. In this work, we characterize degradation of covalent adaptable thioester networks. We form networks by photopolymerizing 8-arm poly(ethylene glycol) (PEG) thiol and PEG-thioester norbornene with 0%, 50% and 100% excess thiol. In these networks, rearrangement of the cross-links is due an exchange reaction that takes place between excess thiols and network cross-links. The exchange reaction can be tuned by varying the amount of excess thiol in the network. Using multiple particle microrheology (MPT), we characterize degradation of thioester networks initiated by incubation in L-cysteine, which has a single thiol group that cannot participate in network cross-linking when the exchange reaction occurs. MPT measures Brownian motion of florescent probe particles embedded in a network. We use time-cure superposition (TCS) to calculate the critical relaxation exponent, n, for thioester networks with varying amounts of excess thiol. The value of n is indicative of the network microstructure with n<0.5 being a tightly cross-linked network and n>0.5 a loosely cross-link network. Our results show that the value of n depends on the amount of excess thiol in the thioester network. For networks with 0% excess thiol, n=0.34±0.07, indicating an elastic network. Thioester networks with 50% unreacted thiol have the lowest value of n, n=0.23±0.04, indicating the material is more elastic than the other networks characterized. Networks with 100% excess thiol have an n value of n=0.53±0.12, indicating this scaffold is similar to an ideal, percolated network. We measure the storage modulus of these networks with bulk rheology and measure a similar trend in modulus of the material as a function of concentration of excess thiol. Networks with 0%, 50% and 100% excess thiol have storage moduli of 390±44 Pa, 504±107 Pa and 281±35 Pa, respectively. These results indicate networks with 50% excess thiol have the highest cross-link density agreeing with MPT results. We also measure stress relaxation in these networks by applying 10% strain and measuring stress in the networks over time. Our results show that there is no significant difference in the extent of stress relaxation in networks with 0% and 100% excess thiol while networks with 50% excess thiol are slower to relax and more. Previous work with thioester networks with different precursors reported decreases in cross-link density with increasing concentration of excess thiol. Thioester networks in our work do not follow this trend. We hypothesize that network non-idealities such as unreacted functional groups and loops reduce the cross-link density. Our work measures changes in network microstructure during degradation as well as macroscopic properties of thioester networks with different amounts of excess thiol. This work can be used to engineer thioester networks for applications that include cell or drug delivery or as a scaffold that promotes wound healing.