title: Enhancing the mechanical properties of engineered tissue through matrix remodeling via the signaling phospholipid lysophosphatidic acid.
abstract: Knee meniscus fibrocartilage is frequently injured, resulting in approximately 1 million procedures annually in the US and Europe. Its near-avascularity contributes heavily to its inability to heal, and places it as a prime candidate for replacement through regenerative medicine. Here, we describe a novel approach to increase extracellular matrix organization, rather than content, in order to augment the mechanical properties of engineered tissue. To synthesize fibrocartilage, we employ a self-assembling process, which is free of exogenous scaffolds and relies on cell-to-cell interactions to form all-biologic constructs. When treated with the signaling phospholipid lysophosphatidic acid (LPA), tissue constructs displayed increased tensile properties and collagen organization, while total collagen content remained unchanged. LPA-treated constructs exhibited greater DNA content, indicative that the molecule exerted a signaling effect. Furthermore, LPA-treated cells displayed significant cytoskeletal reorganization. We conclude that LPA induced cytoskeletal reorganization and cell-matrix traction, which resulted in matrix reorganization and increased tensile properties. This study emphasizes the potential of non-traditional stimuli, such as signaling phospholipids, for use in tissue development studies. The extension of these results to other collagen-rich tissues represents a promising avenue for future exploration.
authors: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors: Pasha
authors: P
authors: Hadidi
authors: Kyriacos A
authors: KA
authors: Athanasiou
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000187:drug effects* / Q000502:physiology*; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D019245:Compressive Strength / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects* / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D023822:Tissue Engineering
chemical_list: D008246:Lysophospholipids; D003094:Collagen; C032881:lysophosphatidic acid