ch7_harl_celforc

ch7_harl_celforc - Harvard-MIT Division of Health Sciences...

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Measuring Cell Contraction Cell Force Monitor Brendan Harley 2.785J/3.97J/BEH.411J/HST.523J Massachusetts Institute of Technology March 11, 2004 Courtesy of Brendan Harley. Used with permission. Harvard-MIT Division of Health Sciences and Technology HST.523J: Cell-Matrix Mechanics Prof. Myron Spector Prof. Ioannis Yannas
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 2 Clinical Application • Wound healing following severe injury: Repair – Wound contraction • Myofibroblasts ( Į -SMA) – Synthesis of scar tissue • Anisotropic tissue • Significantly stiffer, reduced range of motion, pain, inferior functional properties • Bioactive scaffolds developed to induce regeneration – Cell continuity is practically absent – Contractile cells are randomly oriented within the bioactive scaffold – Hypothesis: the structure of the bioactive ECM analog prevents the coordinated cell contraction that results in wound contraction and scar formation Yannas, 2001
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 3 Development of Bioactive Scaffolds Bioactive scaffolds engineered to induce an appropriate or desired cell response in vitro or in vivo Requires critical adjustment of four physical and structural properties : 1. Chemical composition (ligands) 2. Average pore size 3. Degradation rate 4. For induced regeneration: Collagen fiber structure Yannas, 2001
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 4 Bioactive Scaffold: Pore Size • Scaffold bioactivity is significantly affected by pore structure – Large enough to allow cells to migrate into the structure – Small enough to establish a sufficiently high specific surface area • Non-uniform scaffolds – Patches of scaffold are inactive • Fabrication of a uniform scaffold – Uniform activity throughout scaffold – Study cell-scaffold interactions at a microscopic scale Figure by MIT OCW. After Yannas et al., 1989. 0.1 1 0 10 10 20 30 100 1000 1cm Average Pore Diameter, µ m Wound Half-life, Days ungrafted control
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 5 Design of Cell/Tissue Specific Biomaterials • Material and structural properties significantly affect cell behavior – Different cell types respond differently to different scaffolds • Architecture mediated? • Stiffness mediated? • Composition mediated? • Degradation rate mediated? • How do cells detect and respond to their surrounding environments ( i.e. , mechanical, structural, chemical) and what are the critical cues? – Cell-mediated contraction Nehrer et al., 1997 Yannas, 2001 Salem et al., 2002 Claase et al. 2003
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 6 Single Cell Mechanics on 2-D Substrates • Study behavior of a single cell on a flat membrane ( i.e. , silicone, polyacrylamide) – Mechanical environment ( i.e. , system stiffness) – Chemical environment ( i.e. , ligands, growth factors, cytokines) • Experimental tools: – Microscopic analysis of membrane deflection
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2/16/2005 B. Harley Measuring Cell Contraction March 11, 2004 7 Single Cell Mechanics on 2-D Substrates
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ch7_harl_celforc - Harvard-MIT Division of Health Sciences...

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