Ples (19 vs. 21 2 (initial) and 19 1 (caged)). Thus, it is hypothesized that the presence of the cage in these studies did not affect the overall trends seen or the hypothesized degradation mechanism. Although there was evidence of increased degradation of our PEGDA samples at 4 week without cages, the magnitude of this effect still did not correlate with those seen by Lynn et al., in which they were unable to retrieve 80 of their samples at 4 weeks due to complete degradation. Finally, the differences between the murine and rat inflammatory responses may have contributed to some of the noted inconsistences between the two studies. It is most likely that the combination of reduced crosslinking efficiency, lack of cage, and change in animal model contributed to the increased degradation observed by Lynn et al. When comparing the in vivo data to the accelerated hydrolytic data in our studies, 1 day in 5 mM NaOH at 37 was approximately equivalent to 3 weeks in vivo in the cage implant system. Thus, it is likely that if the study had included an additional time point at 16 weeks, a loss in mechanical integrity would have been observed at that time, and complete dissolution of implants would have occurred at approximately 280 weeks. While these comparisons are useful for this system, one should keep in mind that differences in degradation rates exist between implant locations and that device geometry can also impact degradation. [20] In particular, Reid et al. recently demonstrated that PEG hydrogels elicit an enhanced immune response when implanted in contact with adipose tissue than they do when implanted subcutaneously. This enhanced immune response would result in increased concentrations of degradative agents and is hypothesized to increase in vivo degradation rates. Thus, the correlations found in these studies cannot be directly utilized for all types of PEGDA implants. However, this is the first in vivo degradation study with PEGDA hydrogels that was carried out to a point of significant degradation to confirm that they are not useful for long-term implantable applications, and it provides a general time frame over which PEGDA gels can retain their initial properties in vivo. An additional consideration is the impact of these findings on the more recently developed hydrolytically degradable PEG hydrogels. These can be formed via Michael-type addition of multifunctional thiol or amine moieties with PEGDA or in a two step reaction. In the latter, an initial Michael-type addition between PEGDA and a dithiol or amine is used to form acrylate-terminated PEG chains which is then followed by photocrosslinking step to form the hydrogel network.Eteplirsen The resulting gels degrade on a much faster time scale than photocrosslinked PEGDA hydrogels.Amikacin sulfate [37, 38] Degradation rates can be tuned from weeks to months with the two step reaction introducing more esters and undergoing fasterJ Biomed Mater Res A.PMID:24633055 Author manuscript; available in PMC 2015 December 01.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBrowning et al.Pagedegradation. Differences in the resulting network and the hydrophobicity of the netpoints can potentially influence degradation rate; however, Schoenmakers et al. reported decreasing hydrolysis half life with decreasing number of methylene units between the ester bond and the sulfide which was also correlated with increased atomic charge on the carbon atom of the ester bond. [39, 40] Therefore, it is likely that.
