title: Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells.
abstract: Scaffold-based delivery of bioactive molecules capable of directing stem cell differentiation is critical to the development of point-of-care cell therapy for orthopedic repair. Dexamethasone-conjugated hyaluronic acid (HA-DXM) was synthesized and combined with hydrolytically degradable, photo-cross-linkable PEG-bis(2-acryloyloxy propanoate) (PEG-bis-AP) to form semi-IPNs. Dexamethasone (DX) release was limited in physiological buffer and substantially increased in the presence of encapsulated human mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming that release occurred primarily by a cell-mediated enzymatic mechanism. hMSCs encapsulated in PEG-bis-AP/HA-DXM semi-IPNs increased osteoblast-specific gene expression, alkaline phosphatase activity, and matrix mineralization, attaining levels that were not significantly different from positive controls consisting of hMSCs in PEG-bis-AP/native HA cultured with DX supplementation in the culture medium. These studies demonstrate that PEG-bis-AP/HA-DXM semi-IPNs can provide cell-mediated release of bioactive free DX that induces hMSC osteogenic differentiation. This approach offers an efficient system for local delivery of osteogenic molecules empowering point of care applications.
authors.affiliation: Microenvironmental Engineering Laboratory and ‡Drug Design, Development, and Delivery Laboratory, Department of Bioengineering, Clemson University , 301 Rhodes Research Center, Clemson, South Carolina 29634, United States.
authors.forename: Sooneon
authors.initials: S
authors.lastname: Bae
authors.affiliation: Microenvironmental Engineering Laboratory and ‡Drug Design, Development, and Delivery Laboratory, Department of Bioengineering, Clemson University , 301 Rhodes Research Center, Clemson, South Carolina 29634, United States.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Microenvironmental Engineering Laboratory and ‡Drug Design, Development, and Delivery Laboratory, Department of Bioengineering, Clemson University , 301 Rhodes Research Center, Clemson, South Carolina 29634, United States.
authors.forename: Jeoung Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Microenvironmental Engineering Laboratory and ‡Drug Design, Development, and Delivery Laboratory, Department of Bioengineering, Clemson University , 301 Rhodes Research Center, Clemson, South Carolina 29634, United States.
authors.forename: Ken
authors.initials: K
authors.lastname: Webb
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: D003692:Delayed-Action Preparations; D003907:Dexamethasone