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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 CELL-MATRIX MECHANICS M. Spector, Ph.D. and I.V. Yannas, Ph.D. TISSUE Tissue is a biological structure made up of cells of the same type. Cells of the same phenotype (i.e., same genes expressed). An aggregation of morphologically similar cells and associated extracellular matrix acting together to perform one or more specific functions in the body. There are four basic types of tissue: muscle, nerve, epithelia, and connective. An organ is a structure made up of 2 or more tissues. Articular Cartilage Extracellular Matrix Figures by MIT OCW. Cell 4 mm 10 m CELL-MATRIX MECHANICS How cells respond to mechanical force Load-deformation of the matrix How cells generate mechanical forces One effect that an exogenous mechanical force can have on cells (a and b; chondrocytes) and the generation of mechanical force by cells (c and d; chondrocytes). Four images removed for copyright reasons. (a) A typical chondrocyte (approximately 10 micron in diameter) in articular cartilage viewed by a transmission electron microscopy. The application of a mechanical force to cartilage causes compression of a chondrocyte by 20% (b) The compression results in a compaction and anisotropic organization of organelles such as the Golgi apparatus and the rough endoplasmic reticulum responsible for the synthesis of extracellular matrix molecules. Alterations in the organelles as a result of compression can change the structure of the matrix molecules that they synthesize. (c) and (d). Light microscopy images of living chondrocytes seeded into a collagenglycosaminoglycan scaffold, followed over a 300-min period after seeding. (c) Up to 40 minutes after being seeded the chondrocytes show a rounded phenotype (the 2 cells on the horizontal strut in the middle of the image. (d) After 5 hours the cells noticeably spread on the fine member to which they were attached and buckled the strut as a result of their contraction. Bending of the members to which the shortened strut was attached is noticeable. The strut to which the cells were attached reduced in length from approximately 144 micron (c) to 89 micron after 5 hours (d) representing a reduction of almost 40%. Sources: (a) and (b) from M.A. DiMicco, et al., "Response of the chondrocyte to mechanical stimuli" in Pathogenesis of Osteoarthritis. (c) and (d) from J. Zaleskas, et al., Biomat. 2004;25:1299. UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Figure by MIT OCW. Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator "Control Volume" UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Cell Biology Subjects Regulator Figure by MIT OCW. Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator "Control Volume" UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Figure by MIT OCW. Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator Biomaterials "Control Volume" 2.79 UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Mechanical Exogenous Force (Strain); MF Physical Regulator Figure by MIT OCW. 2.785 Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator "Control Volume" UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Mechanical Force (Strain); Physical Regulator 2.785 Figure by MIT OCW. Cell + Matrix Molecules (Insoluble Reg.) UCP: Contraction Product + Soluble Mech. Force Regulator Endogenous MF "Control Volume" UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Mechanical Force (Strain); Physical Regulator UCP: Contraction Cell + Matrix Molecules Product + Soluble Mech. Force Regulator Shield cells from stress Deformed by cell Excessively load cells Biomaterials/ contraction Promote cell contraction Implants UNIT CELL PROCESSES The "Control Volume" and Regulators Mechanical Force (Strain); Physical Regulator Cell + Matrix Molecules (Insoluble Reg.) Figures by MIT OCW. The strain experienced by the cell will depend on the loaddeformation behavior (modulus of elasticity) of the Matrix CELL-MATRIX MECHANICS How cells respond to mechanical force Load-deformation of the matrix How cells generate mechanical forces UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Cell Biology Subjects Regulator Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator "Control Volume" Bone (Trabecular) Structure Normal Osteoporotic: Postmenopausal Photo removed for copyright reasons. Photo removed for copyright reasons. Bone Remodeling J NIH 7:88 (1995) Courtesy of The Journal of the National Institutes of Health. Used with permission. Bone Remodeling Courtesy of The Journal of the National Institutes of Health. Used with permission. J NIH 7:88 (1995) UNIT CELL PROCESSES The "Control Volume" and Regulators Chemical (Soluble) Regulator Mechanical Force (Strain); Physical Regulator UCP: Contraction Cell + Matrix Molecules Product + Soluble Mech. Force Regulator Shield cells from stress Deformed by cell Excessively load cells Biomaterials/ contraction Promote cell contraction Implants CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Shielding cells from stress Excessively loading cells Promoting cell contraction How cells generate mechanical forces Deformation of biomaterials/implants CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Shielding cells from stress Joint replacement prostheses Knee and Hip Replacement with Prostheses Photos removed for copyright reasons. CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Excessively loading cells Tissue expanders (soft tissue) Distraction osteogenesis (bone lengthening) Ultrasound stimulation of fracture healing CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Excessively loading cells Tissue expanders (soft tissue) http://www.breastreconstruction.ca/implant.htm Tissue expansion is a process that stretches the skin in preparation for the placement of a permanent implant later. Depending on whether one is dealing with an immediate or a delayed reconstruction, the tissue expander is either placed at the time of the mastectomy or during a subsequent procedure. Tissue Expanders for Breast Reconstruction Photo removed for copyright reasons. Photo removed for copyright reasons. Schematic showing the position of the tissue expander under the pectoralis major muscle. Intraoperative view of the tissue expander placed underneath the pectoralis major muscle. Photo removed for copyright reasons. Photo removed for copyright reasons. Schematic shows the position of the tissue expander and three stages in its expansion. At the completion of expansion the permanent breast implant will be inserted in a similar location. Photo removed for copyright reasons. Intraoperative view of the tissue expanders being inflated. CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Excessively loading cells Distraction osteogenesis (bone lengthening) Limb Lengthening Distraction Osteogenesis Photos removed for copyright reasons. Gavriel Illizarov, M.D., Russian Orthopaedic Surgeon http://www.ilizarov.com/english/limb_lenghtening.asp Insertion of the intramedullary nail and osteotomy; The corticotomy is completed percutaneous with a corticotome. Application of the external fixator Photo removed for copyright reasons. Distraction (the method of taking the bony fragments away from each other) is started in the tenth day. The rate of the distraction should be 0.25 mm four times a day. Photo removed for copyright reasons. Sacrifice 5 days after a 13-day distraction period Rat Model Photos removed for copyright reasons. Kinner B, et al. J. Orthop. Res. 2003;21:20 Cranial Deformation Photos removed for copyright reasons. CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Excessively loading cells Ultrasound stimulation of fracture healing Sonic Accelerated Fracture Healing System Exogen 2000 Low-intensity ultrasound (lower than a fetal sonogram) Accelerates fracture healing by 38% Prescribed by physicians Used by patients at home or work 20 minute treatment time once per day Osteoporosis Studies New and unique mechanical stress technology Non-pharmaceutical therapy Subject of pre-clinical studies Demonstrated prevention of bone loss and increase in bone mass (animal studies) Currently being studied in post-menopausal women Clinical Use Prescribed for more than 15,000 fractures Prescribed by over 6,000 physicians Reimbursed by more than 800 insurers Source: http://ortho.smith-nephew.com/au/Category.asp?NodeId=2480 The Role of Ultrasound in Fracture Healing See Smith & Nephew slide presentation online at http://ortho.smith-nephew.com/nl/Category.asp?NodeId=1453 (last accessed 25 January 2005) CELL-MATRIX MECHANICS Clinical Examples/Medical Devices How cells respond to mechanical force Promoting cell contraction How cells generate mechanical forces Deformation of biomaterials/implants Tissue contracture Scar Contracture after a Burn Injury Photos removed for copyright reasons. What cells are responsible for this? Treatments? Food and Drug Administration Breast Implant Complications Photographs of Breast Implant Complications http://www.fda.gov/cdrh/breastimplants/breast_implants_photos.html FDA has developed this website for displaying photographs and/or illustrations of breast implant complications. This website is not intended to be photographic representation of all breast implant complications. FDA will continue to add photographs and/or illustrations of complications associated with saline-filled and silicone gelfilled implants as they become available. You should refer to the breast implant consumer handbook, which is available on the FDA breast implant website at http://www.fda.gov/cdrh/breastimplants/ for a description of potential breast implant complications. http://www.fda.gov/cdrh/breastimplants/breast_implants_photos.html BREAST IMPLANTS Capsular Contracture Capsular contracture occurs when the scar tissue or capsule that normally forms around the implant tightens and squeezes the implant. It may be more common following infection, hematoma (collection of blood), and seroma (collection of watery portion of blood). There are four grades of capsular contracture. The Baker grading is as follows Grade I the breast is normally soft and looks natural Grade II the breast is a little firm but looks normal Grade III the breast is firm and looks abnormal (visible distortion) Grade IV the breast is hard, painful, and looks abnormal (greater distortion) Additional surgery may be needed to correct the capsular contracture. This surgery ranges from removal of the implant capsule tissue to removal (and possibly replacement) of the implant itself. Capsular contracture may happen again after this additional surgery. Breast Implant Position and "Capsular Contraction" Diagrams removed for copyright reasons. Boston Globe, July 22, 1991 Fibroblasts with contractile capacity cause contracture of the fibrous tissue BREAST IMPLANTS Capsular Contracture Photo removed for copyright reasons. Photograph shows Grade IV capsular contracture in the right breast of a 29year-old woman seven years after subglandular (on top of the muscle and under the breast glands) placement of 560cc silicone gel-filled breast implants. BREAST IMPLANTS Capsular Contracture Removed implant: viewing the outside of the fibrous capsule Photo removed for copyright reasons. Photo removed for copyright reasons. Inside of the fibrous capsule Photo removed for copyright reasons. Implant Photo removed for copyright reasons. http://www.implantforum.com/capsular-contracture/ BREAST IMPLANTS Capsular Contracture What is Capsular Contracture? Scar tissue that forms around the implant which causes the breasts to harden (similar to what a contracted muscle feels like) as the naturally forming scar tissue around the implant tightens and squeezes it. While capsular contracture is an unpredictable complication, it is also the most common complication of breast augmentation. How can Capsular Contracture be prevented? Textured implants help deter contracture because of their rough surface which is intended to discourage a hard capsule from forming. Under the muscle (sub-pectoral or 'partial sub-muscular') placement of the implant reduces risk of capsular contracture by an average of 8 - 10%. Whereas over the muscle (in front of the muscle or 'sub-mammary') has 10 - 25% or more chance of capsule contracture. http://www.implantforum.com/capsular-contracture/ BREAST IMPLANTS Capsular Contracture How can Capsular Contracture be prevented? Massage and or compression. This is usually only done with smooth implants and may be suggested for a period between a few weeks to as long as you have your implants. Do not massage bruises! The "no-touch" technique. This method includes meticulously rewashing surgical gloves before handling any instrument and implants. Only the head surgeon touches the implant, using a unique Teflon cutting board and immediately inserting the implant underneath the muscle. All of these measures help ensure that no foreign substance attach themselves to the implant, which could inflame the surrounding tissue and cause complications such as capsular contracture. CELL-MATRIX MECHANICS How cells respond to mechanical force Load-deformation of the matrix How cells generate mechanical forces UNIT CELL PROCESSES The "Control Volume" and Regulators Exogenous MF Which cells respond to MF? What are the responses? What are the mechanisms? - Merely related to production of a reg.? Cell + Matrix Molecules (Insoluble Reg.) UCP Product + Soluble Regulator UNIT CELL PROCESSES The "Control Volume" and Regulators Which cells are capable of contraction? What are the regulators? What are the mechanisms of contraction? Cell + Matrix Molecules (Insoluble Reg.) UCP: Contraction Product + Soluble Mech. Force Regulator Endogenous MF ...
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