Transcript Biomaterials_Lecture 7

BIOMATERIALS
ENT 311/4
LECTURE 7
Tissue Reaction to Biomaterials:
Foreign Body Reaction
Immune Response to Biomaterials
Infection and Tumorigenesis of
Biomaterials
Prepared by: Nur Farahiyah Binti Mohammad
Date: 14th August 2008
Email : [email protected]
Teaching Plan
Objective
Describe, discuss and
illustrate inflammation,
wound healing, foreign
body reaction, blood
material interaction and
tumorgenesisi.
DELIVERY
MODE
•Lecture
•Tutorial
•Supplement
reading
LEVEL OF
COMPLEXITY
•Knowledge
•Repetition
•Application
COURSE OUTCOME
COVERED
•Ability to explain and
illustrate tissue reaction
to biomaterials
EFFECT OF MATERIAL ON HOST
TISSUE
The main cellular host response to
injury are:
2.1
2.2
2.3
Inflammation
Wound healing response
Foreign body reaction
Sequence of host
reaction
following
implantation of
medical devices
or biomaterial
INJURY
HEMOSTASIS
INFLAMMATION
Acute
Inflammation
Chronic
Inflammation
PROLIFERATION
PROLIFERATION
(granulation tissue)
(granulation tissue)
REMODELLING
SCAR TISSUE or FIBROUS
CAPSULE DEVELOPMENT
FOREIGN BODY GIANT
CELL FORMATION
Acute
Chronic
Granulation tissue
The predominant cell type that present in the
cellular host response
2.3 FOREIGN BODY REACTION EVENT
INJURY
HEMOSTASIS
ACUTE INFLAMMATION
CHRONIC
INFLAMMATION
PROLIFERATION
(granulation tissue
formation
FOREIGN BODY
GIANTCELLS FORMATION
2.3 FOREIGN BODY REACTION
(FBR)
DEFINITION OF FBR
FBR is an inflammatory reaction evoke by
the presence of foreign material in the
tissues, characterized by the formation
of foreign body giant cells.
2.3 FOREIGN BODY REACTION
(FBR)
• The foreign body reaction begins as
wound healing, including stoppage of
bleeding, infiltration of inflammatory
cells to debride the area, and the
formation of granulation tissue.
• However, the persistent presence of a
biomedical implant, splinter,
particulates, or other foreign bodies
inhibits full healing.
2.3 FOREIGN BODY REACTION
(FBR)
• Rather than the resorption and
reconstruction that occurs in wound
healing, the foreign body reaction is
characterized by:
– The formation of foreign body giant cells,
– Encapsulation of the foreign object
– Formation of granulation tissue that
consist of macrophages, fibroblasts and
capillaries.
2.3 FOREIGN BODY REACTION
(FBR)
What is it Foreign body giant cell?
• Foreign body giant cells are the
products formed by the fusion of
monocytes and macrophage in
attempt to phagocytose the material.
2.3 FOREIGN BODY REACTION
(FBR)
What happened?
• When macrophages encounter a
foreign object too large to be
phagocytosed, such as an implant, it is
thought that the macrophages
experience “frustrated phagocytosis.”
• They fuse to form larger foreign body
giant cells composed of up to a few
dozen individual macrophages.
2.3 FOREIGN BODY REACTION
(FBR)
• Giant cells secrete degradative agents
such as superoxides and free radicals,
causing localized damage to implants
and other foreign bodies.
2.3 FOREIGN BODY REACTION
(FBR)
• Macrophages and foreign body giant
cells tend to remain at the surface of
an implant for the duration of its
residence.
• Encapsulation refers to the firm,
generally a vascular collagen shell
deposited around a foreign body,
effectively isolating it from the host
tissues.
• This response was developed as a
protective measure.
2.3 FOREIGN BODY REACTION
(FBR)
• Encapsulation is especially
problematic for devices designed to
interact with the body, such as
glucose sensors.
• The foreign body reaction can lead to
chronic pain and device rejection and
failure.
2.3 FOREIGN BODY REACTION
(FBR)
• The composition of the foreign body
reaction determined by:
– Surface properties of the biomaterials
– The form of the implant
– The relationship between the surface area
of the biomaterial and the volume of the
implant.
• Example: high surface-to-volume implant such
as fabrics, porous material, particulate or
micro-spheres will have higher ratios of
macrophages and foreign body giant cells in
the implant site than smooth-surface implants.
2.3 FOREIGN BODY REACTION
(FBR)
G = Foreign Body Giant cell
M= Macrophage
F = Fibroblast
Foreign body giant
cell surround the
foreign material
Foreign material
3.0 Immune Response to
Biomaterial
• Function of immune system:
–
To defend the host against infectious
organism.
• The immune system protects
organisms from infection with
layered defenses of increasing
specificity.
• The layered defenses consists of:
1. Innate Immunity
2. Adaptive Immunity
3.0 Immune Response to Biomaterial
INNATE IMMUNITY
• Refers to generalized set of defences
that do not require recognition of
foreign substance.
• Physical barrier:
– Skin and mucosa serve as physical barriers
to microbe.
3.0 Immune Response to Biomaterial
• Complement system
– the complement cascade provide
mechanism for microbial killing.
– Complement: family of plasma proteins
that are activated by an enzymatic
cascade.
3.0 Immune Response to Biomaterial
– The end result of this cascade is the assembly of
five activated protein called the membrane attack
complex (MAC) in the plasma membrane of the
microbes.
– The proteins work together to:
• trigger the recruitment of inflammatory cells.
• "tag" pathogens for destruction by other cells by
opsonizing, or coating, the surface of the pathogen.
• disrupt the plasma membrane of an infected cell,
resulting in cytolysis of the infected cell, causing the
death of the pathogen.
• rid the body of neutralized antigen-antibody complexes.
3.0 Immune Response to Biomaterial
• Cellular barriers
– Activation of phagocytic cell such as
macrophage and neutrophils.
– Activation of lymphocyte-natural killer
cell.
– These cells serve to engulf and destroy
foreign particles and microbes by
targeting them into intracellular
lysosomes.
3.0 Immune Response to Biomaterial
ADAPTIVE IMMUNITY
• Has two way of defence:
– Cell mediated immunity
– Humoral mediated immunity
• This serve to
– enhance innate immunity
– present specialization by focusing the immune
response on specific targets with antibodies and
T-cells.
– Provide immunologic memory by producing a
more rapid and amplified response upon
repeated exposure to targets.
3.0 Immune Response to Biomaterial
• Cell-mediated immunity
– Has two major mechanism
• Helper T-lymphocytes
• Cytotoxic T-lymphocytes
– Antigen-specific T-lymphocyte recognize
foreign intracellular antigens on the
surface of an infected macrophage.
– The helper T-lymphocytes activates the
infected macrophage by secreting
cytokines to cause elimination of
intracellular microbes by reactive oxygen
and chemical species
3.0 Immune Response to Biomaterial
– Some cells are not capable of eliminating
intracellular microbes (like macrophage).
– So, these cells killed by cytotoxic Tlymphocytes in order to illuminate the
microbe.
• Humoral immunity
– Functions by recognition of foreign
substance (antigen) by antigen-specificantibodies.
– Once activated, B-lymphocytes can
differentiate into plasma cells, which
produced secreted, antigen-specific
antibodies.
– This antibodies bind to the antigen and
both activate complement and promote
phagocytosis by coating the foreign
substance.
• Conceptually, humoral immunity
should be thought as a way of
attacking extra cellular foreign
substance.
3.0 Immune Response to
Biomaterial
• Main feature of Innate and Adaptive Immunity
Innate
Adaptive
Physical/chemical
barriers
Skin, mucosal epithelium,
antimicrobial chemicals
Lymphocyte in
epithelia, secreted
antibodies
Onset
Exposure lead to immediate
response
Lag time between
exposure and response
Type of immunity
Surface barrier or mucosal
immunity , cell barrier
Cell mediated and
humoral component.
Memory
No immunological memory
Exposure leads to
immunological memory
Cells
Phagocytes (macrophages,
neutrophils), nature killer cells,
B-lymphocytes (B cell)
Helper T-lymphocytes
Cytotoxic T-lymphocyte
(T cell)
3.0 Immune Response to
Biomaterial
 Both innate and adaptive immunity depend on the
ability of the immune system to distinguish
between self and non-self molecules.
 In immunology, self molecules are those
components of an organism's body that can be
distinguished from foreign substances by the
immune system.
 Conversely, non-self molecules are those
recognized as foreign molecules. One class of nonself molecules are called antigens (short for
antibody generators) and are defined as substances
that bind to specific immune receptors and elicit an
immune response.
3.0 Immune Response to
Biomaterial
• Cell-mediated immunity is an
immune response that does not
involve antibodies or complement but
rather involves the activation of
macrophages, natural killer cells (NK),
antigen-specific cytotoxic Tlymphocytes, and the release of
various cytokines in response to an
antigen.
3.0 Immune Response to
Biomaterial
• The Humoral Immune Response (HIR) is
mediated by proteins called antibodies that
are produced by B lymphocyte (B cell).
• Secreted antibodies bind to antigens on the
surfaces of invading microbes (such as
viruses or bacteria), which flags them for
destruction.
• Humoral immunity is called as such,
because it involves substances found in the
humours, or body fluids.
4.0 INFECTION AND TUMORIGENESIS
OF BIOMATERIALS
• Serious complication that can occur
due to the presence of biomaterial in
the body are:
4.1 Hypersensitivity
4.2 Infection
4.3 Tumorigenesis
4.1 Hypersensitivity
• Also known as allergic reaction
• Is undesired immune response
mediated by the adaptive immune
response.
• Defined as unusual, excessive, or
uncontrolled immune reaction.
4.2 Infection
• Can occur on or surrounding any type of
implant.
• Characteristic of implant-associated
infection:
– Presence of biomaterial
– Bacterial colonization of tissue
– Resistance to host defence mechanisms and
antibiotic therapy
– Presence of multiple bacteria species
– Absence of integration of the biomaterial with
the host
– Presence of cell damage
4.2 Infection
• Stages that involved in development
of implant-associated infection:
1. Attachment: bacterial attachment to the
surface occurs through non-specific
interaction between the pathogen and
the surface.
2. Adhesion: the preliminary attachment
becomes permanent as specific
receptor-ligand interactions develop and
nonspesific interaction remains.
4.2 Infection
3. Aggregation: the bacteria devide after
firmly attaching to the surface, causing
the development of biofilm
(polysaccharide slime) .
 This biofilm protect the micro organisms
from phagocytosis by neutrophils or tissue
macrophages and provide a favourable
environment for bacterial growth.
4. Dispersion: The bacteria travel from the
colony to other areas of the body.
4.3 Tumorigenesis
• Tumorigenesis is the formation of
tumours.
• Tumor is composed of uncontrolled
proliferating cell.
• Type of tumor:
– Benign tumor: do not invade adjacent
tissue or spread to distant site.
– Malignant tumor: Do invade surrounding
tissues and gain entry into lymph and
blood vessels.
4.3 Tumorigenesis
2. Latency
Time period varies (15-20
years for human)
1.Initiation
Implantation of biomaterial = malignant
transformation of DNA
Due to:
Chemical carcinogenesis (chemicals leached from
implant)
OR
Foreign body carcinogenesis (mechanism
unknown, may be related to surface or bulk
properties of the implant or alterations in local
environment.
3. Promotion
Obvious tumor
growth around
implant
4.3 Tumorigenesis
• Two main routes of malignant
transformation:
1) Chemical carcinogenesis is possible
near biomaterials since tumors may be
caused by substance that have leached
from the implant.
4.3 Tumorigenesis
2) Foreign body carcinogenesis may be
related to surface or bulk properties of
the implant or alterations in local
environment.
•
Possible cause are:
– Bulk chemical properties of the implant
– Physiochemical surface properties of the
implant
– Viral contamination of the implant
– Interruption of cellular communication
due to the presence of the implant
– Local tissue damage leading to
insufficient nutrient exchange