(598d) Rheological Characterization of Degradation of Covalent Adaptable Thioester Networks

Covalent adaptable networks are being designed for applications such as cell delivery, drug delivery and dissolvable wound sealants. These adaptable networks have cross-links that can be rearranged when external chemical or physical stimuli, such as additional molecules or shear, are present. To design adaptable networks for delivery or wound healing applications, it is important to characterize material degradation. In this work, we characterize degradation of covalent adaptable thioester networks using multiple particle tracking microrheology (MPT) and bulk rheology. Thioester networks are covalent adaptable due to a thioester exchange reaction between unreacted thiols and network cross-links. Here, we form networks with 8-arm poly(ethylene glycol) (PEG)-thiol and PEG-thioester norbornene with 0%, 50% and 100% unreacted thiol. Network degradation is initiated by incubating the scaffold with L-cysteine and this dynamic process is characterized by MPT. MPT measures Brownian motion of fluorescently labeled probe particles embedded in these networks. Using time-cure superposition we measure the critical relaxation exponent, n, for network degradation with varying amounts of unreacted thiol. The value of n relates to the microstructure of the network during degradation. Our results show the critical relaxation exponent is dependent on the amount of unreacted thiol in the network. Thioester networks with 50% unreacted thiol have the lowest value of n which is 0.23±0.04, indicating the material is more elastic than the other networks characterized. Networks with 100% unreacted thiol have an n value of 0.53±0.12, indicating this scaffold is similar to an ideal, percolated network. For networks with no unreacted thiol the n value measured is 0.34±0.07, again indicating an elastic network. We measure the equilibrium storage moduli of these networks with bulk rheology and a similar trend is measured. Networks with 100% unreacted thiol have the lowest elastic modulus of 273±14 Pa indicating these scaffolds have the lowest cross-link density. Networks with 50% and 0% unreacted thiol, which MPT indicated are elastic networks, have higher storage moduli, 580±6 Pa and 456±8 Pa, respectively. We also measure stress relaxation of these networks by applying 10% strain and measuring the stress over time. These experiments show there is no significant difference in stress relaxation between networks with 0% and 100% unreacted thiol but networks with 50% unreacted thiol are more elastic. These results differ from previously reported work that characterized thioester networks. By increasing the amount of unreacted thiol in the thioester networks, previous work hypothesized that the cross-linking density decreases. Therefore, networks without unreacted thiols should be the most elastic. We hypothesize that these materials do not follow these trends because of non-idealities in the network structure during scaffold gelation, such as loops or unreacted functional groups, which reduces the cross-link density. This work shows the effect of the amount of unreacted thiol in the network on the macroscopic properties and network microstructure during degradation. These results can be used in the design of these networks for cell or drug encapsulation and wound healing because it will enable scaffold degradation to be tuned to deliver encapsulated cargo to a target or control network architecture for tissue engineering.