Massachusetts Institute of Technology Harvard Medical School Brigham and Women’s Hospital VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J BIOMATERIALS-TISSUE INTERACTIONS: INTRODUCTION 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. Cell Extracellular Matrix 4 mm 10 μm Articular Cartilage ENGINEERING ? Production of a product for human good using existing knowledge. – Science is the process of acquisition of new knowledge. – Technology is the means by which products are produced. BIOMATERIALS-TISSUE INTERACTIONS Permanent versus Absorbable Biomaterials ? Roles of permanent biomaterials for the production of permanent implants versus the roles as absorbable scaffolds for tissue engineering BIOMATERIALS-TISSUE INTERACTIONS Effects of Biomaterials on Tissue ? In Bulk Form – Tissue formation – Attachment – Remodeling ? In Particle (Molecular) Form – Tissue degradation BIOMATERIALS-TISSUE INTERACTIONS Effects of Biomaterials on Cells ? In Bulk Form – Cell attachment – Cell proliferation (mitosis) – Production of matrix molecules and enzymes (synthesis) – Migration – Contraction – Release of pre-packaged reactive molecules (exocytosis) ? In Particle (Molecular) Form – Ingestion of particles (endocytosis) BIOMATERIALS-TISSUE INTERACTIONS Permanent Biomaterials ? Positive Response – Tissue attachment ? Adverse Responses – Contraction – Reaction to particles; tissue destruction ? Passive Response Total Hip and Knee Replacement Prostheses Images removed due to copyright considerations BIOMATERIALS-TISSUE INTERACTIONS Permanent Biomaterials ? Positive Response – Tissue attachment ? Adverse Responses – Contraction – Reaction to particles; tissue destruction ? Passive Response 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 gel- filled 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” Images removed due to copyright considerations Contracted Fibrous Tissue Capsule Boston Globe, July 22, 1991 BREAST IMPLANTS Capsular Contracture Image removed due to copyright considerations Capsular contraction Photograph shows Grade IV capsular contracture in the right breast of a 29- year-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 Implant Capsule Inside of the fibrous capsule Implant Images removed due to copyright considerations 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. BIOMATERIALS-TISSUE INTERACTIONS Permanent Biomaterials ? Positive Response – Tissue attachment ? Adverse Responses – Contraction – Reaction to particles; tissue destruction ? Passive Response “Small Particle Disease” Particles Released From Implants Newsweek, April 29, 1991 Images removed due to copyright considerations Sci. 295:1994 (2002) BIOMATERIALS-TISSUE INTERACTIONS Permanent versus Absorbable Biomaterials ? Roles of permanent biomaterials for the production of permanent implants versus the roles as absorbable scaffolds for tissue engineering BIOMATERIALS-TISSUE INTERACTIONS Absorbable Biomaterials ? Materials as scaffolds for tissue engineering Image of newspaper clipping – removed due to copyright considerations. Laura Meckler, “Transplant waiting list climbs over 75,000.” Pittsburgh Post-Gazette, March 10, 2001. Articular Cartilage Defects Do Not Heal ? Avascular ? Aneural ? Low cell density ? Cells of low mitotic activity ? Cells cannot freely migrate through the extracellular matrix Articular Cartilage Defects ? Incidence is high and increasing due to increasing activity levels ? Causes pain and disability ? Profoundly impacts the quality of life The Clinical Problem Arthroscopic Debridement “Microfracture” Osteochondral Autograft Cells injected under a tissue or collagen cover Total Knee Replacement Current Clinical Practice Image removed due to copyright considerations Image removed due to copyright considerations Image removed due to copyright considerations Image removed due to copyright considerations Autologous Chondrocyte Implantation Image removed due to copyright considerations This process has been commercialized by Genzyme (for USD$11,500). M Brittberg, et al., NEJM 33:889 (1994) Debridement of the Degenerative Tissue in the Lesion Collagen Membrane Used as Covering Material to Contain the Cells Video clips removed due to copyright considerations Applying and Suturing the Collagen Membrane Injecting the Autologous Chondrocytes grown in Vitro Cells Future Clinical Practice Implementing Tissue Engineering Implantation of a cell-seeded matrix “Tissue engineered” cartilage implanted in a rabbit model did not remodel (Advanced Tissue Sciences, Inc.). Future Clinical Practice Implementing Tissue Engineering Implantation of the matrix alone “Microfracture”: Stem cells from bone marrow infiltrate the defect Image removed due to copyright considerations. Image removed due to copyright considerations. -FGF-2 TISSUE FORMATION AND REMODELING IN VITRO Images removed due to copyright considerations. See Veilleux NH, Yannas IV, Spector M. “Effect of passage number and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes in type I and II collagen-glycosaminoglycan matrices in vitro.” Tissue Eng. 2004 Jan-Feb;10(1-2):119-27. +FGF-2 Canine chondrocytes grown in a type II collagen-GAG scaffold for 2 weeks. (Safranin O stain for GAGs) BIOMATERIALS-TISSUE INTERACTIONS Particles BIOMATERIAL TISSUE 10nm 100nm 1μm 10 μm 100 μm1mm 1 sec 1 day 10 days 100 days Size Scale Time Scale Strength Modulus of Elasticity Fracture mechanics Protein Adsorption Cell Response Ion Release Wear Metal corrosion Polymer degradation BONE Tissue Remodeling Cell-cell interactions ECM proteins Cytokines Eicosanoids Enzymes