(475u) Design of Biodegradable Hydrogel by Nanogel Engineering

In tissue engineering, hydrogels have been intensively studied to deliver the appropriate amount of growth factors or hormones to a target site on desired time scale. We previously reported that cholesterol-bearing pullulan (CHP) formed stable monodisperse hydrogel nanoparticles (nanogel) in water by self-assembly. These nanogels spontaneously formed complexes with various drugs and proteins and served as a promising carrier for these drugs. Recently, we modified CHP nanogel with methacryloyl groups and polymerized with other hydrophilic polymer to prepare the hybrid hydrogel with nanogel domains. The immobilized nanogels retained their ability to encapsulate proteins. In addition, the trapped proteins can be released form hydrogel in an active form (chaperon like activity). Purpose of this study is to fabricate a biodegradable hydrogel with nanogel domains for tissue engineering. We cross-linked acryloyl-group modified CHP (CHPA) nanogels with thiol-group modified poly (ethylene glycol) (pentaerythritol tetra (mercaptoethyl) polyoxyethylene, PEGSH) by Michael addition to prepare hydrogel (CHP-PEG gel). MALS and DLS measurement revealed that 3-4 CHPA molecules, which have 28 acryloyl groups per 100 anhydrous groups, self-assembled to form a relatively monodisperse nanogel with a diameter of 27 nm in water. CHPA nanogel and PEGSH were mixed in phosphate buffered saline at the appropriate volume ratio. Galation occurred within 10 minutes when the final concentration of CHPA nanogels were 30 mg/ml in hydorgel. The water content of CHP-PEG gel was higher than 90v/v%. The cross-section of the hydrogel was observed with TEM. The nanogel structure was maintained after gelation and nanogels distributed homogeneously in the hydrogel. This hydrogel gradually swelled and degraded within 1 week in 10% serum. CHP-PEG gel is expected to serve as a preferable hydrogel with the efficient drug-loading capacity for tissue engineering.