We have created hyaluronic acid (HA)-based doubly crosslinked networks (DXNs) using HA-derived hydrogel particles (HGPs) as the microscopic building blocks. Composed of densely crosslinked HGPs integrated in a loosely connected secondary matrix that is also HA-based, these hydrogels are soft and elastic, exhibiting unique frequency-dependent viscoelasticity. When covalently conjugated with perlecan domain I, HA HGPs allowed for a sustained release of bone morphogenetic protein 2 (BMP-2), effectively inducing the chondrogenic differentiation of mesenchymal stem cells (MSCs). Alternatively, MSCs could adhere to the composite matrix through focal adhesion sites clustered on HGP surfaces that had been previously decorated with cell-binding motifs. These cell-instructive matrices supported MSC proliferation and induced their osteogenic differentiation in the absence of osteogenic factors. TheHA-based hydrogel systems are promising candidates as scaffolding materials for soft tissue regeneration.

Engineered matrices for stem cell differentiation and soft tissue regeneration

244th National Meeting (2012)

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