title: Direct noninvasive measurement and numerical modeling of depth-dependent strains in layered agarose constructs.
abstract: Biomechanical factors play an important role in the growth, regulation, and maintenance of engineered biomaterials and tissues. While physical factors (e.g. applied mechanical strain) can accelerate regeneration, and knowledge of tissue properties often guide the design of custom materials with tailored functionality, the distribution of mechanical quantities (e.g. strain) throughout native and repair tissues is largely unknown. Here, we directly quantify distributions of strain using noninvasive magnetic resonance imaging (MRI) throughout layered agarose constructs, a model system for articular cartilage regeneration. Bulk mechanical testing, giving both instantaneous and equilibrium moduli, was incapable of differentiating between the layered constructs with defined amounts of 2% and 4% agarose. In contrast, MRI revealed complex distributions of strain, with strain transfer to softer (2%) agarose regions, resulting in amplified magnitudes. Comparative studies using finite element simulations and mixture (biphasic) theory confirmed strain distributions in the layered agarose. The results indicate that strain transfer to soft regions is possible in vivo as the biomaterial and tissue changes during regeneration and maturity. It is also possible to modulate locally the strain field that is applied to construct-embedded cells (e.g. chondrocytes) using stratified agarose constructs.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, US.
authors.forename: A J
authors.initials: AJ
authors.lastname: Griebel
authors.affiliation: Orthopaedic Research Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Khoshgoftar
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, US.
authors.forename: T
authors.initials: T
authors.lastname: Novak
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: van Donkelaar
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, US. Electronic address: cpneu@purdue.edu.
authors.forename: C P
authors.initials: CP
authors.lastname: Neu
mesh_terms: D001672:Biocompatible Materials; D002358:Cartilage, Articular / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D012038:Regeneration; D012685:Sepharose; D013314:Stress, Mechanical; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D012685:Sepharose
keywords: Agarose scaffold; Finite element method; Functional tissue engineering; Heterogeneous strains; Imaging elastography