ch2_unitcell

ch2_unitcell - Harvard-MIT Division of Health Sciences and...

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Unformatted text preview: Harvard-MIT Division of Health Sciences and Technology HST.523J: Cell-Matrix Mechanics Prof. Myron Spector Massachusetts Institute of Technology Harvard Medical School Brigham and Women's Hospital VA Boston Healthcare System 2.785j/3.97J/BEH.411/HST523J "UNIT CELL PROCESSES" Tools for Understanding the Molecular, Cellular, and Physiological, Bases of the Tissue Response to Implants M. Spector, Ph.D. and I.V. Yannas, Ph.D. CONCEPTS FOR UNDERSTANDING BIOMATERIALS-TISSUE INTERACTIONS Control Volume Unit Cell Processes Types of Tissues Tissue Formation and Remodeling In Vitro Articular Cartilage Extracellular Matrix Figures by MIT OCW. Cell 4 mm 10 m Chondrocytes (P2 Canine) in a Type I Collagen-GAG Scaffold Photo removed for copyright reasons. "Control Volume" Source: B. Kinner UNIT CELL PROCESSES Concept of a "Control Volume" around a Cell Soluble Regulator A Cell + Matrix (Regulator) Product + Soluble Regulator B "Control Volume" UNIT CELL PROCESSES Concept of a "Control Volume" around a Cell Soluble Mechanical Regulator Loading (Strain) A Cell + Matrix (Regulator) Product + Soluble Regulator B "Control Volume" CONCEPTS FOR UNDERSTANDING BIOMATERIALS-TISSUE INTERACTIONS Control Volume Unit Cell Processes Types of Tissues Tissue Formation and Remodeling In Vitro UNIT CELL PROCESSES Mitosis Migration Synthesis Contraction Endocytosis Exocytosis COLLAGEN-GAG MATRICES: MODEL BIOMATERIALS (ANALOGS OF EXTRACELLULAR MATRIX) Investigation of cell interactions (UCPs) in vitro Type I (bovine and porcine) Type II (porcine) Chondroitin 6-sulfate Photo removed for copyright reasons. 1mm Freeze-dried Dehydrothermally cross-linked Additional cross-linking IV Yannas, et al. PNAS, 1989 Photo removed for copyright reasons. 500m CELL MATRIX INTERACTIONS WITH COLLAGEN-GAG MATRICES IN VITRO Can provide insights into interrelationships among cell processes. How do mitosis and synthesis interrelate? How do mitosis and synthesis relate to contraction? How does migration relate to contraction? Can provide insights into cell behavior in vivo. Can serve as a model in which to investigate the effects of exogenous forces on cells and the contractile behavior of cells (i.e., generating endogenous force). Chondrocytes (Passage 2 Canine) in a Type I Collagen-GAG Matrix Photo removed for copyright reasons. J. Cheng UNIT CELL PROCESSES Mitosis Migration Synthesis Contraction Endocytosis Exocytosis Chondrocyte (P2 Canine) in a Type I Collagen-GAG Matrix: Mitosis Photo removed for copyright reasons. J. Cheng UNIT CELL PROCESSES Mitosis Migration Synthesis Contraction Endocytosis Exocytosis Chondrocytes (P2 Canine) in a Type I CollagenGAG Matrix: Migration and Contraction Photo removed for copyright reasons. B. Kinner, in JM Zaleskas Biomat. 2004;25:1299 Image removed for copyright reasons. See Figure 6 in Mitchison and Cramer. "Actin-Based Cell Motility and Cell Locomotion." Cell 84:371 (1996) Two Models for Generation of Traction Force Using Myosin II Activity In the contraction model (A), myosin pulling on filaments of opposite polarity creates a cortical tension that pulls the cell equally in all directions. This contraction can be converted into movement by combining it with preferential assembly of the cortex at the front of the cell and disassembly at the back, and/or by regulating the relative strength of adhesive contacts to the substratum at the front and back. In the transport model (B), myosin activity pulls the body of the cell over an oriented track of actin filaments attached to the substratum. UNIT CELL PROCESSES Mitosis Migration Synthesis Contraction Endocytosis Exocytosis Chondrocytes (P2 Canine) in a Type I Collagen-GAG Matrix: Contraction Photo removed for copyright reasons. Photo removed for copyright reasons. 40 min B. Kinner, in JM Zaleskas Biomat. 2004;25:1299 300 min Non-Seeded: 8 days Cell-Seeded: 8 days Photo removed for copyright reasons. Photo removed for copyright reasons. 10mm 21 days Non-Seeded and Cell-Seeded Collagen-GAG Scaffolds Photo removed for copyright reasons. S. Vickers Human Articular Chondrocytes in Monolayer Culture IH - Green: -smooth muscle actin; Orange: type II collagen Photo removed for copyright reasons. Chondrocytes express the gene for -smooth muscle actin and this enables them to contract B. Kinner, et al. JOR 2001;19:233 -Smooth Muscle Actin Immunohistochemistry of Human Articular Cartilage Photo removed for copyright reasons. Neg. control Kim and Spector, JOR 2000;18:749 MUSCULOSKELETAL CELLS THAT CAN EXPRESS -SMOOTH MUSCLE ACTIN AND CAN CONTRACT Articular chondrocyte Osteoblast Meniscus fibroblast and fibrochondrocyte Intervertebral disc fibroblast and fibrochondrocyte Ligament fibroblast Tendon fibroblast Synovial cell M. Spector, Mesenchymal stem cell Wound Repair Regen. 9:11-18 (2001) POSSIBLE ROLES FOR -SMOOTH MUSCLE ACTIN-ENABLED CONTRACTION Musculoskeletal Connective Tissue Cells Tissue engineering Contracture of scaffolds Healing Closure of wounds (skin wounds and bone fractures) Disease processes Contracture (Dupuytren's) Tissue formation Modeling of ECM architecture and remodeling (e.g., crimp in ligament/tendon?) CONCEPTS FOR UNDERSTANDING BIOMATERIALS-TISSUE INTERACTIONS Control Volume Unit Cell Processes Types of Tissues Tissue Formation and Remodeling In Vitro Wound Healing In Vivo TYPES OF TISSUES Which Tissues Can Regenerate Spontaneously? Yes Connective Tissues Bone Articular Cartilage, Ligament, Intervertebral Disc, Others Epithelia (e.g., epidermis) Muscle Cardiac, Skeletal Smooth Nerve No BIOMATERIALS-TISSUE INTERACTIONS Cell + Matrix Connective Tissue Epithelia Muscle Nerve UNIT CELL PROCESSES Concept of a "Control Volume" around a Cell Soluble Mechanical Regulator Loading (Strain) A Cell + Matrix (Regulator) Product + Soluble Regulator B "Control Volume" BIOMATERIALS-TISSUE INTERACTIONS Cell + Matrix Connective Tissue Epithelia Muscle Nerve Adhesion Protein Collagen Biomaterial BIOMATERIALS-TISSUE INTERACTIONS Cell + Matrix Connective Tissue Epithelia Muscle Nerve Adhesion Protein Collagen Biomaterial Integrin "UNIT CELL PROCESSES" UCP Cell + Matrix Connective Tissue Epithelia Muscle Nerve Mitosis Synthesis Migration Contraction Endocytosis Exocytosis "UNIT CELL PROCESSES" Cell + Matrix Connective Tissue Epithelia Muscle Nerve UCP Product Mitosis Synthesis Cell proliferation Matrix molecules, enzymes, cytokines Migration Translocation Contraction Strain Endocytosis Solubilized fragments Exocytosis Regulators "UNIT CELL PROCESSES" Regulator UCP Cell + Matrix Connective Tissue Epithelia Muscle Nerve Product + Regulator Mitosis Synthesis Migration Contraction Endocytosis Exocytosis Cytokines (Growth Factors) "UNIT CELL PROCESSES" Regulator Mechanical Force (Strain) UCP Cell + Matrix Connective Adhesion Tissue Protein Epithelia Collagen Muscle Biomaterial Nerve Integrin Product + Regulator Mitosis Synthesis Migration Contraction Endocytosis Exocytosis Cytokines (Growth Factors) "UNIT CELL PROCESSES" Regulator Mechanical Force (Strain) UCP Cell + Matrix Connective Adhesion Tissue Protein Epithelia Collagen Muscle Biomaterial Nerve Integrin Product + Regulator Mitosis Synthesis Migration Contraction Endocytosis Exocytosis Cytokines (Growth Factors) "UNIT CELL PROCESSES" Regulator (TGF-1) UCP Cell + Matrix Connective Adhesion Tissue Protein Epithelia Collagen Muscle Biomaterial Nerve Integrin Product + Regulator Mitosis Synthesis Migration Matrix strain Cytokines (contracture/ (Growth Factors) shrinkage) Contraction Endocytosis Exocytosis "UNIT CELL PROCESSES" TGF-1 Contraction Fibroblast + Collagen Contracture + Reg. CONCEPTS FOR UNDERSTANDING BIOMATERIALS-TISSUE INTERACTIONS Control Volume Unit Cell Processes Types of Tissues Tissue Formation and Remodeling In Vitro Wound Healing In Vivo -FGF-2 TISSUE FORMATION AND REMODELING IN VITRO Photo removed for copyright reasons. +FGF-2 Canine chondrocytes grown in a type II collagen-GAG scaffold for 2 weeks. (Safranin O stain for GAGs) Photo removed for copyright reasons. N. Veilleux UNIT CELL PROCESSES BONE REMODELING Degradation Osteoclast + ECM Synthesis: collagenase, H+ Sol. ECM + Reg. Formation Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING Reg. Osteoclast + ECM Synthesis: collagenase, H+ Sol. ECM + Reg. Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING Reg. Osteoclast + ECM Synthesis: collagenase, H+ Sol. ECM + Reg. Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING Reg. Osteoclast + ECM Synthesis: collagenase, H+ Sol. ECM + Reg. Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING IL-1, PGE2 Osteoclast + ECM PGE2 Synthesis: collagenase, H+ TGF- Synthesis: collagen Sol. ECM + Reg. Osteoblast + ECM New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING IL-6 Osteoclast + ECM Precursor Cells Migration More OCs + Reg. Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING Reg. MF No Effect Osteoclast + ECM MF Synthesis: collagenase, H+ Sol. ECM + Reg. Osteoblast + ECM Synthesis: collagen New ECM + Reg. UNIT CELL PROCESSES BONE REMODELING Osteoblast + ECM Osteoblast + ECM (-) MF (-)Synthesis: collagen (+) MF (+)Synthesis: collagen Less ECM + Reg. (?) More ECM + Reg. (?) UNIT CELL PROCESSES BONE REMODELING Degradation MF Fibroblast + ECM MF Synthesis: collagenase Sol. ECM + Reg. Formation Fibroblast + ECM Synthesis: collagen New ECM + Reg. ...
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This note was uploaded on 11/11/2011 for the course BIO 20.410j taught by Professor Rogerd.kamm during the Spring '03 term at MIT.

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