Cell-Mediated Dexamethasone Release from Semi-IPNs\nStimulates Osteogenic Differentiation of Encapsulated Mesenchymal\nStem Cells

Abstract

Scaffold-based\ndelivery of bioactive molecules capable of directing\nstem cell differentiation is critical to the development of point-of-care\ncell therapy for orthopedic repair. Dexamethasone-conjugated hyaluronic\nacid (HA-DXM) was synthesized and combined with hydrolytically degradable,\nphoto-cross-linkable PEG-bis­(2-acryloyloxy propanoate) (PEG-bis-AP)\nto form semi-IPNs. Dexamethasone (DX) release was limited in physiological\nbuffer and substantially increased in the presence of encapsulated\nhuman mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming\nthat release occurred primarily by a cell-mediated enzymatic mechanism.\nhMSCs encapsulated in PEG-bis-AP/HA-DXM semi-IPNs increased osteoblast-specific\ngene expression, alkaline phosphatase activity, and matrix mineralization,\nattaining levels that were not significantly different from positive\ncontrols consisting of hMSCs in PEG-bis-AP/native HA cultured with\nDX supplementation in the culture medium. These studies demonstrate\nthat PEG-bis-AP/HA-DXM semi-IPNs can provide cell-mediated release\nof bioactive free DX that induces hMSC osteogenic differentiation.\nThis approach offers an efficient system for local delivery of osteogenic\nmolecules empowering point of care applications.