Cross-linking and degradation of step-growth hydrogels formed by thiol-ene photoclick chemistry.
Thiol-ene photoclick hydrogels have been used for a variety of tissue engineering and controlled release applications. In this step-growth photopolymerization scheme, four-arm poly(ethylene glycol) norbornene (PEG4NB) was cross-linked with dithiol containing cross-linkers to form chemically cross-linked hydrogels. While the mechanism of thiol-ene gelation was well described in the literature, its network ideality and degradation behaviors are not well-characterized. Here, we compared the network cross-linking of thiol-ene hydrogels to Michael-type addition hydrogels and found thiol-ene hydrogels formed with faster gel points and higher degree of cross-linking. However, thiol-ene hydrogels still contained significant network nonideality, demonstrated by a high dependency of hydrogel swelling on macromer contents. In addition, the presence of ester bonds within the PEG-norbornene macromer rendered thiol-ene hydrogels hydrolytically degradable. Through validating model predictions with experimental results, we found that the hydrolytic degradation of thiol-ene hydrogels was not only governed by ester bond hydrolysis, but also affected by the degree of network cross-linking. In an attempt to manipulate network cross-linking and degradation of thiol-ene hydrogels, we incorporated peptide cross-linkers with different sequences and characterized the hydrolytic degradation of these PEG-peptide hydrogels. In addition, we incorporated a chymotrypsin-sensitive peptide as part of the cross-linkers to tune the mode of gel degradation from bulk degradation to surface erosion.
Department of Biomedical Engineering, Purdue School of Engineering and Technology, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana 46202, United States.
Han
H
Shih
Chien-Chi
CC
Lin
D000465:Algorithms; D002918:Chymotrypsin / Q000737:chemistry; D057930:Click Chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D008970:Molecular Weight; D009636:Norbornanes / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D055668:Photochemical Processes; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D059748:Proteolysis; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D003432:Cross-Linking Reagents; D020100:Hydrogels; D009636:Norbornanes; D009842:Oligopeptides; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D002918:Chymotrypsin; D004229:Dithiothreitol