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