(540a) Cytocompatibility Evaluation of Novel Thermoresponsive and Chemically Crosslinkable Macromers for Injectable, In Situ Forming Hydrogels | AIChE

(540a) Cytocompatibility Evaluation of Novel Thermoresponsive and Chemically Crosslinkable Macromers for Injectable, In Situ Forming Hydrogels

Authors 

Klouda, L. - Presenter, Rice University
Hacker, M. C. - Presenter, Rice University
Kretlow, J. D. - Presenter, Rice University
Mikos, A. G. - Presenter, Rice University


Injectable hydrogels provide promising carriers for cell and drug delivery in tissue engineering due to their hydrophilic nature, minimally invasive method of delivery and the ability to fill irregular defects. In this category, thermally responsive hydrogels have the advantage of using temperature as the stimulus for their solidification. They can be liquid at ambient temperature, and gel upon injection in the human body while temperature increases to physiological. However, hydrogels made from exclusively hydrophilic polymers often suffer from limited mechanical stability restricting their use in orthopedic applications. In this study towards the development of injectable hydrogels of controllable and improved mechanical properties, we present the characterization of novel injectable macromers that contain hydrophobic domains for mechanical reinforcement and functionalities for chemical crosslinking in situ. The macromers are designed to exhibit physical gelation at physiological temperature, and the introduction of (meth)acrylate groups allows for subsequent chemical crosslinking. Macromers were synthesized from pentaerythritol diacrylate monostearate, N-isopropylacrylamide, acrylamide and 2-hydroxyethyl acrylate by free radical polymerization. At a next step, the free hydroxyl groups on the macromers were (meth)acrylated. Macromer composition was verified by NMR spectroscopy, and oscillating rheology was employed to characterize the thermally induced phase transition and the resulting gels. It was shown that the degree of modification with (meth) acrylate groups correlated with the transition temperature of the macromers. Cytocompatibility studies on the (meth)acrylated macromers over 24 h revealed that higher degrees of modification increased toxicity; however cell viability was high for up to six hours for most formulations. Moreover, acrylated macromers seemed more cytocompatible than the corresponding methacrylates. These results show potential for the fabrication of hydrogels that solidify almost instantaneously due to physical thermogelation in physiological temperature, and can subsequently slowly crosslink with the addition of thermal initiators in a time interval and manner that does not prove toxic for encapsulated cells.