title: Mimicking Cartilage Tissue Zonal Organization by Engineering Tissue-Scale Gradient Hydrogels as 3D Cell Niche.
abstract: Zonal organization plays an important role in cartilage structure and function, whereas most tissue-engineering strategies developed to date have only allowed the regeneration of cartilage with homogeneous biochemical and mechanical cues. To better restore tissue structure and function, there is a strong need to engineer materials with biomimetic gradient niche cues that recapitulate native tissue organization. To address this critical unmet need, in this study, we report a method for rapid formation of tissue-scale gradient hydrogels as a three-dimensional (3D) cell niche with tunable biochemical and physical properties. When encapsulated in stiffness gradient hydrogels, both chondrocytes and mesenchymal stem cells demonstrated zone-specific response and extracellular deposition that mimics zonal organization of articular cartilage. Blocking cell mechanosensing using blebbistatin abolished the zonal response of chondrocytes in 3D hydrogels with a stiffness gradient. Such tissue-scale gradient hydrogels can provide a 3D artificial cell niche to enable tissue engineering of various tissue types with zonal organizations or tissue interfaces.
authors.affiliation: 1 Department of Bioengineering, Stanford University , Stanford, California.
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhu
authors.affiliation: 2 Department of Orthopaedic Surgery, Stanford University , Stanford, California.
authors.forename: Xinming
authors.initials: X
authors.lastname: Tong
authors.affiliation: 3 Department of Biology, Stanford University , Stanford, California.
authors.forename: Pavin
authors.initials: P
authors.lastname: Trinh
authors.affiliation: 1 Department of Bioengineering, Stanford University , Stanford, California.|2 Department of Orthopaedic Surgery, Stanford University , Stanford, California.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D032701:Biomimetics; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D020100:Hydrogels / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020100:Hydrogels
keywords: cartilage; gradient; hydrogels; interfacial tissue engineering; zonal organization