title: Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes.
abstract: Hydrogel precursors are liquid solutions that are prone to leaking after surgical placement. This problem was overcome by incorporating either decellularized cartilage (DCC) or devitalized cartilage (DVC) microparticles into traditional photocrosslinkable hydrogel precursors in an effort to achieve a paste-like hydrogel precursor. DCC and DVC were selected specifically for their potential to induce chondrogenesis of stem cells, given that materials that are chondroinductive on their own without growth factors are a revolutionary goal in orthopedic medicine. We hypothesized that DVC, lacking the additional chemical processing steps in DCC to remove cell content, would lead to a more chondroinductive hydrogel with rat bone marrow-derived mesenchymal stem cells. Hydrogels composed of methacrylated hyaluronic acid (MeHA) and either DCC or DVC microparticles were tested with and without exposure to transforming growth factor (TGF)-β3 over a 6 week culture period, where swelling, mechanical analysis, and gene expression were observed. For collagen II, Sox-9, and aggrecan expression, MeHA precursors containing DVC consistently outperformed the DCC-containing groups, even when the DCC groups were exposed to TGF-β3. DVC consistently outperformed all TGF-β3-exposed groups in aggrecan and collagen II gene expression as well. In addition, when the same concentrations of MeHA with DCC or DVC microparticles were evaluated for yield stress, the yield stress with the DVC microparticles was 2.7 times greater. Furthermore, the only MeHA-containing group that exhibited shape retention was the group containing DVC microparticles. DVC appeared to be superior to DCC in both chondroinductivity and rheological performance of hydrogel precursors, and therefore DVC microparticles may hold translational potential for cartilage regeneration.
authors.affiliation: 1 Department of Surgery, University of Kansas Medical Center , Kansas City, Kansas.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Beck
authors.affiliation: 2 Department of Molecular Biosciences, University of Kansas , Lawrence, Kansas.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Barragan
authors.affiliation: 3 Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas.
authors.forename: Tony B
authors.initials: TB
authors.lastname: Libeer
authors.affiliation: 4 Department of Mechanical Engineering, University of Kansas , Lawrence, Kansas.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kieweg
authors.affiliation: 5 Cardiac Surgery Research Laboratory, Children's Mercy Hospital , Kansas City, Missouri.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Converse
authors.affiliation: 5 Cardiac Surgery Research Laboratory, Children's Mercy Hospital , Kansas City, Missouri.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopkins
authors.affiliation: 3 Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas.|6 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Berkland
authors.affiliation: 4 Department of Mechanical Engineering, University of Kansas , Lawrence, Kansas.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D003432:Cross-Linking Reagents / Q000494:pharmacology; D055119:Elastic Modulus / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006820:Hyaluronic Acid / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D008422:Materials Testing; D008689:Methacrylates / Q000494:pharmacology; D009824:Ointments; D017207:Rats, Sprague-Dawley; D012212:Rheology / Q000187:drug effects; D013552:Swine
chemical_list: D003432:Cross-Linking Reagents; D008689:Methacrylates; D009824:Ointments; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid