title: Dexamethasone Release from Within Engineered Cartilage as a Chondroprotective Strategy Against Interleukin-1α.
abstract: While significant progress has been made toward engineering functional cartilage constructs with mechanical properties suitable for in vivo loading, the impact on these grafts of inflammatory cytokines, chemical factors that are elevated with trauma or osteoarthritis, is poorly understood. Previous work has shown dexamethasone to be a critical compound for cultivating cartilage with functional properties, while also providing chondroprotection from proinflammatory cytokines. This study tested the hypothesis that the incorporation of poly(lactic-co-glycolic acid) (PLGA) (75:25) microspheres that release dexamethasone from within chondrocyte-seeded agarose hydrogel constructs would promote development of constructs with functional properties and protect constructs from the deleterious effects of interleukin-1α (IL-1α). After 28 days of growth culture, experimental groups were treated with IL-1α (10 ng/mL) for 7 days. Reaching native equilibrium moduli and proteoglycan levels, dexamethasone-loaded microsphere constructs exhibited tissue properties similar to microsphere-free control constructs cultured in dexamethasone-supplemented culture media and were insensitive to IL-1α exposure. These findings are in stark contrast to constructs containing dexamethasone-free microspheres or no microspheres, cultured without dexamethasone, where IL-1α exposure led to significant tissue degradation. These results support the use of dexamethasone delivery from within engineered cartilage, through biodegradable microspheres, as a strategy to produce mechanically functional tissues that can also combat the deleterious effects of local proinflammatory cytokine exposure.
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Brendan L
authors.initials: BL
authors.lastname: Roach
authors.affiliation: 2 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Arta
authors.initials: A
authors.lastname: Kelmendi-Doko
authors.affiliation: 3 Department of Orthopedics and Sports Medicine, Mount Sinai Health System , New York, New York.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Balutis
authors.affiliation: 2 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.|4 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.|5 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.|6 Department of Mechanical Engineering, Columbia University , New York, New York.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Ateshian
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Clark T
authors.initials: CT
authors.lastname: Hung
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D065546:Drug Liberation; D053582:Interleukin-1alpha / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020011:Protective Agents / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D053582:Interleukin-1alpha; D020011:Protective Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone