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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 LIGAMENTS AND TENDONS M. Spector, Ph.D. CELL-MATRIX MECHANICS Effects of mechanical forces on cells (including the response to removing forces) Load-deformation behavior of the tissue Histological make-up of the tissue to derive structure-properties relationships Endogenous force generated by cells TOPICS Microanatomy/Histology Molecular composition of the ECM Hierarchical structure Mechanical properties Response to injury and healing potential Response to mechanical loading JOINT TISSUES Structure - Function Relationships ECM Architecture - Mechanical Function INTRAARTICULAR VERSUS EXTRAARTICULAR LIGAMENTS What are the unique characteristics of the joint environment? Why don't these tissues heal? INTRAARTICULAR ENVIRONMENT Synovial fluid Dissolves the fibrin clot Absence of surrounding vascularized tissue COMARISON OF JOINT TISSUES
Tissue Cell Round/ Loading Type Type Lac. Coll. Art. Cart. Comp. Hyal. Chond. Yes II Cart. Meniscus C/T Fibro- Fibro- Yes I Cart. Chond. ACL Tens. Fibrous Fibro- No I Tissue blast * Inner third ** Mid-substance PG Vasc. Heal. +++ 0 0 0/+ 0 0* 0** 0 0 Ligament: Histology Diagram removed for copyright reasons. Ligament: Polarized Light Microscopy Diagram removed for copyright reasons. Ligament: ECM Hierarchical Architecture Diagram removed for copyright reasons. Rat tail tendon viewed under polarized light microscopy while undergoing tensile testing Graphs and photos removed for copyright reasons. A Viidik, 1980 -smooth muscle actin in fibroblasts in the healing rabbit collateral ligament 10 wks
Diagram and photo removed for copyright reasons. Faryniarz, Chaponnier, Gabbiani, Yannas, and Spector; JOR, 14:228 (1996) 10% cells SMA+ Myofibroblasts in the Healing Rabbit Medial Collateral Ligament (10 wks post-rupture)
Faryniarz, Chaponnier, Gabbiani, Yannas, and Spector; JOR, 14:228 (1996) Smooth muscle actin Photos removed for copyright reasons. Myofibroblasts draw the ruptured ends together and tension the ligament. SMA-containing cells in the intact human ACL SMA (red) Up to 50% cells SMA+
Diagram and photos removed for copyright reasons. no SMA Neg. Control; antibody MM Murray, et al., JOR, 1999;17:18-27 Histologic Changes in the Human ACL after Rupture Diagram removed for copyright reasons. A. Inflammation B. Epiligamentous Regeneration C. Proliferation D. Remodeling
M. Meaney Murray, et al., J. Bone Jt. Surg., 2000;82-A:1387 Ruptured Human Anterior Cruciate Ligaments
Photo removed for copyright reasons. Evidence supporting the hypothesis that SMA-enabled contraction is responsible for retraction of the ruptured ends. Crimped morphology of SMA-containing (red) cells consistent with contraction. Imparting crimp to matrix? Photo removed for copyright reasons. M. Meaney Murray, et al. J. Bone Jt. Surg., 2000;82-A:1387 The Migration of Human Anterior Cruciate Ligament Fibroblasts into Porous Collagen-GAG Matrices In Vitro
M. M. Murray, D. Schultz-Torres, S. D. Martin, and M. Spector Department of Orthopaedic Surgery Brigham and Women's Hospital Harvard Medical School Boston, MA Graphs and diagrams removed for copyright reasons. See results published in these two papers: 1) Meaney Murray M, Martin SD, and Spector M. The migration of cells from human anterior cruciate ligament explants into collagen-glycosaminoglycan scaffolds. J. Orthop. Res. 2000;18:557-564. 2) Murray MM and Spector M. The migration of cells from the ruptured human anterior cruciate ligament into collagenglycosaminoglycan regeneration templates in vitro. Biomat. 2001;22:2393-2402. Results: 2-D Culture
Outgrowth start time
10 + 0.5 days for explants from intact ACLs 8 + 2 days for explants from ruptured ACLs Rates of outgrowth
0.23 mm/day for explants from intact ACLs 0.25 mm/day for explants from ruptured ACLs Results: 3-D Culture
Maximum cell number density in scaffold at 2 weeks
462 + 169 cells/mm2 for explants from intact 333 + 161 cells/mm2 for explants from ruptured Maximum cell number density in scaffold at 4 weeks
652 + 330 cells/mm2 for explants from intact 903 + 360 cells/mm2 for explants from ruptured Figure by MIT OCW. After Fung. Ruptured Human Rotator Cuff Is SMA-enabled contraction responsible for retraction of the ruptured ends?
Photos removed for copyright reasons. Neg. Control J. Premdas, et al. JOR, 2001;19:221-228 TENDON AND LIGAMENT
Limitations to Healing Absence of a fibrin clot Absent or low vascularity Dissolution of clot in synovial fluid (ACL) Cell migration restricted by matrix Low cell density Low mitotic activity Mechanical loading disrupts stroma LIGAMENT
Stress Deprivation (Immobilization): Biochemical Changes Water content Total GAG Collagen mass Collagen turnover (degradation and synthesis) Collagen cross-linking ...
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- Spring '03