title: Time-dependent functional maturation of scaffold-free cartilage tissue analogs.
abstract: One of the most critical parameters in cartilage tissue engineering which influences the clinical success of a repair therapy is the ability to match the load-bearing capacity of the tissue as it functions in vivo. While mechanical forces are known to positively influence the development of cartilage matrix architecture, these same forces can induce long-term implant failure due to poor integration or structural deficiencies. As such, in the design of optimal repair strategies, it is critical to understand the timeline of construct maturation and how the elaboration of matrix correlates with the development of mechanical properties. We have previously characterized a scaffold-free method to engineer cartilage utilizing primary chondrocytes cultured at high density in hydrogel-coated culture vessels to promote the formation of a self-aggregating cell suspension that condenses to form a cartilage-like biomass, or cartilage tissue analog (CTA). Chondrocytes in these CTAs maintain their cellular phenotype and deposit extracellular matrix to form a construct that has characteristics similar to native cartilage; however, the mechanical integrity of CTAs had not yet been evaluated. In this study, we found that chondrocytes within CTAs produced a robust matrix of proteoglycans and collagen that correlated with increasing mechanical properties and decreasing cell-matrix ratios, leading to properties that approached that of native cartilage. These results demonstrate a unique approach to generating a cartilage-like tissue without the complicating factor of scaffold, while showing increased compressive properties and matrix characteristics consistent with other approaches, including scaffold-based constructs. To further improve the mechanics of CTAs, studies are currently underway to explore the effect of hydrodynamic loading and whether these changes would be reflective of in vivo maturation in animal models. The functional maturation of cartilage tissue analogs as described here support this engineered cartilage model for use in clinical and experimental applications for repair and regeneration in joint-related pathologies.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Mohanraj
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Farran
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA; Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation, Davos, Switzerland; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA; Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation, Davos, Switzerland. Electronic address: gdodge@upenn.edu.
authors.forename: George R
authors.initials: GR
authors.lastname: Dodge
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002356:Cartilage / Q000502:physiology; D002417:Cattle; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D011509:Proteoglycans; D003094:Collagen
keywords: Cartilage biomechanics; Cartilage tissue engineering; Cell self-aggregation; Scaffold-free