Benzylaminated dextran-modified hydrogels: a long-term bioactive TGF-beta1 carrier

Highly porous dextran-based hydrogels [in which various amounts (up to 16.6%, w/w) of a benzylaminated dextran (DMCB) exhibiting high affinity for TGFbeta1 was immobilized] were developed to achieve long-term retention of bioactive TGFbeta1 in situ. Unmodified hydrogels rapidly desorbed 80-90% compared with only 40-60% of the preloaded TGFbeta1 from the DMCB-modified hydrogels during a period of 21 days in PBS in vitro. TGFbeta1 release experiments (performed with high ionic strength solutions) indicated that formation of the complex between TGFbeta1 and functionalized hydrogels was governed by different interactions, depending on the degree of conjugation with DMCB: ionic interactions in the case of weakly conjugated matrices and nonionic interactions in highly conjugated matrices. Using cells containing a TGFbeta-sensitive luciferase reporter gene, weakly DMCB-modified hydrogels sequestered bioactive TGFbeta1 in situ, giving much higher, long-term signaling performance than highly functionalized hydrogels. Because these biocompatible functionalized hydrogels can provide long-term bioactive TGFbeta1, they could be used as scaffolds for cells to stimulate and regulate human tissue repair processes.