title: Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel.
abstract: Despite significant advances in stem cell differentiation and tissue engineering, directing progenitor cells into three-dimensionally (3D) organized, native-like complex structures with spatially-varying mechanical properties and extra-cellular matrix (ECM) composition has not yet been achieved. The key innovations needed to achieve this would involve methods for directing a single stem cell population into multiple, spatially distinct phenotypes or lineages within a 3D scaffold structure. We have previously shown that specific combinations of natural and synthetic biomaterials can direct marrow-derived stem cells (MSC) into varying phenotypes of chondrocytes that resemble cells from the superficial, transitional, and deep zones of articular cartilage. In this current study, we demonstrate that layer-by-layer organization of these specific biomaterial compositions creates 3D niches that allow a single MSC population to differentiate into zone-specific chondrocytes and organize into a complex tissue structure. Our results indicate that a three-layer polyethylene glycol (PEG)-based hydrogel with chondroitin sulfate (CS) and matrix metalloproteinase-sensitive peptides (MMP-pep) incorporated into the top layer (superficial zone, PEG:CS:MMP-pep), CS incorporated into the middle layer (transitional zone, PEG:CS) and hyaluronic acid incorporated in the bottom layer (deep zone, PEG:HA), creates native-like articular cartilage with spatially-varying mechanical and biochemical properties. Specifically, collagen II levels decreased gradually from the superficial to the deep zone, while collagen X and proteoglycan levels increased, leading to an increasing gradient of compressive modulus from the superficial to the deep zone. We conclude that spatially-varying biomaterial compositions within single 3D scaffolds can stimulate efficient regeneration of multi-layered complex tissues from a single stem cell population.
authors: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
authors: Lonnissa H
authors: LH
authors: Nguyen
authors: Abhijith K
authors: AK
authors: Kudva
authors: Neha S
authors: NS
authors: Saxena
authors: Krishnendu
authors: K
authors: Roy
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002358:Cartilage, Articular / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019245:Compressive Strength; D005109:Extracellular Matrix / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen