title: Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels.
abstract: Degenerative disease and damage to articular cartilage represents a growing concern in the aging population. New strategies for engineering cartilage have employed mesenchymal stem cells (MSCs) as a cell source. However, recent work has suggested that chondrocytes (CHs) produce extracellular matrix (ECM) with superior mechanical properties than MSCs do. Because MSC-biomaterial interactions are important for both initial cell viability and subsequent chondrogenesis, we compared the growth of MSC- and CH-based constructs in three distinct hydrogels-agarose (AG), photocrosslinkable hyaluronic acid (HA), and self-assembling peptide (Puramatrix, Pu). Bovine CHs and MSCs were isolated from the same group of donors and seeded in AG, Pu, and HA at 20 million cells/mL. Constructs were cultured for 8 weeks with biweekly analysis of construct physical properties, viability, ECM content, and mechanical properties. Correlation analysis was performed to determine quantitative relationships between formed matrix and mechanical properties for each cell type in each hydrogel. Results demonstrate that functional chondrogenesis, as evidenced by increasing mechanical properties, occurred in each MSC-seeded hydrogel. Interestingly, while CH-seeded constructs were strongly dependent on the 3D environment in which they were encapsulated, similar growth profiles were observed in each MSC-laden hydrogel. In every case, MSC-laden constructs possessed mechanical properties significantly lower than those of CH-seeded AG constructs. This finding suggests that methods for inducing MSC chondrogenesis have yet to be optimized to produce cells whose functional matrix-forming potential matches that of native CHs.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Erickson
authors.forename: Alice H
authors.initials: AH
authors.lastname: Huang
authors.forename: Cindy
authors.initials: C
authors.lastname: Chung
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Li
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology / Q000293:injuries / Q000502:physiology; D002417:Cattle; D002454:Cell Differentiation; D048430:Cell Shape; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000502:physiology; D006820:Hyaluronic Acid; D020100:Hydrogels; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D010455:Peptides; D012685:Sepharose; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D010455:Peptides; D006820:Hyaluronic Acid; D012685:Sepharose