BIOMATERIALS-TISSUE TISSUE INTERACTIONS: INTRODUCTION

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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 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( 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 Cell 4 mm 10 µm

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 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 TISSUE INTERACTIONS Effects of Biomaterials on Tissue In Bulk Form Tissue formation Attachment Remodeling In Particle (Molecular) Form Tissue degradation

BIOMATERIALS-TISSUE TISSUE INTERACTIONS Effects of Biomaterials on Cells In Bulk Form Cell attachment Cell proliferation (mitosis( mitosis) Production of matrix molecules and enzymes (synthesis( synthesis) Migration Contraction Release of pre-packaged packaged reactive molecules (exocytosis( exocytosis) In Particle (Molecular) Form Ingestion of particles (endocytosis( endocytosis)

BIOMATERIALS-TISSUE 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 TISSUE INTERACTIONS Permanent Biomaterials Positive Response Tissue attachment Adverse Responses Contraction Reaction to particles; tissue destruction Passive Response

http://www.fda Food and Drug Administration Breast Implant Complications Photographs of Breast Implant Complications 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 fda.gov/cdrh/breastimplants/ for a description of potential breast implant complications.

http://www.fda 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 m 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. ture. This surgery ranges from removal of the implant capsule tissue to removal (and possibly replacement) of the implant itself. Capsular contracture e 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 Capsular contraction Image removed due to copyright considerations 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 implantforum.com/capsular-contracture/ 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 n forming scar tissue around the implant tightens and squeezes it. While capsular contracture is an unpredictable complication, it is also o 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 implantforum.com/capsular-contracture/ 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 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 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 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.

The Clinical Problem Articular Cartilage Defects Incidence is high and increasing due to increasing activity levels Causes pain and disability Profoundly impacts the quality of life Articular Cartilage Defects Do Not Heal Avascular Aneural Low cell density Cells of low mitotic activity Cells cannot freely migrate through the extracellular matrix

Arthroscopic Debridement Microfracture Image removed due to copyright considerations Image removed due to copyright considerations Osteochondral Autograft Current Clinical Practice Image removed due to copyright considerations Image removed due to copyright considerations Total Knee Replacement Cells injected under a tissue or collagen cover

M Brittberg, et al., NEJM 33:889 (1994) Autologous Chondrocyte Implantation Image removed due to copyright considerations This process has been commercialized by Genzyme (for USD$11,500).

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 Image removed due to copyright considerations. Image removed due to copyright considerations. Microfracture : Stem cells from bone marrow infiltrate the defect

-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)

BIOMATERIAL Strength Modulus of Elasticity Fracture mechanics BIOMATERIALS-TISSUE TISSUE INTERACTIONS TISSUE Size Scale 10nm nm 100nm nm 1µmµm 10 µm 100 µm1mm mm 1 sec 1 day 10 days 100 days Protein Adsorption Tissue Remodeling Particles Time Scale BONE Wear Metal corrosion Polymer degradation Ion Release Cell-cell Cell interactions Response ECM proteins Cytokines Eicosanoids Enzymes