Host Reactions to Biomaterials I

Introduction
• All implants interact with the biological
environment around them
• Effects go both ways
 Important Notes
1. Tissue immunogenicity does not necessarily
induce immunologically mediated
dysfunctions
2. Specific immunological responses can be not
only a cause of but can result from device
failure
3. The presence of mononuclear cells does not
necessarily denote a rejection pathogenesis.
Mechanical Effects of Host on Implant
• Abrasive wear
• Fatigue
• Stress-corrosion cracking
• Corrosion
• Degeneration and dissolution
 Biological Effects of Host on Implants
• Absorption of substances from tissue
• Enzymatic degradation
• Calcification
 Local Effect of Implant on Host
• Blood material interaction
• Toxicity
• Modification of normal healing
• Infection
• Tumorigenesis
 Systematic Effect of Implant on Host
• Embolization resulting from exposure of blood
to an artificial surface
• Steps of coagulation:
– Plasma protein deposition largely fibrinogen
– Adhesion of platelets to leukocytes (WBC)
– Bulk fibrin formation
 Systematic Effect of Implant on Host
• Hypersensitivity
• Elevation of implant elements in blood (e.g.
metal allergy)
• Lymphatic particle transport: macrophages
transport particulates to lymph nodes and to
lungs
 Local Events Following Implantations
• Injury
• Acute inflammation
• Chronic inflammation
• Granulation tissue
• Foreign body reaction
• Fibrosis
 Infection
• Those associated with medical devices are
resistant to antibiotics and host defense
• Early infections due to unsterile techniques
while late infections are due to blood bourne
bacteria
• The presence of a foreign body potentiates
infection because microbes are provided
access to circulation and deeper tissue
 Infection
• A foreign body increases the chances for
infection by:
– Limiting phagocyte migration into infected tissue
– Interfere with inflammatory cell phagocytic
mechanism through the release of soluble implant
components that allow bacteria to survive
 Inflammation
• The reaction of vascularized living tissue to
local injury
• Goals are:
– To reduce the agent or process causing injury
– To start off healing process by regenerating
parenchymal cells and the formation of
fibroblastic scar tissue
 Inflammation
• After injury there are changes in vascular flow,
caliber, and permeability for exudation
• Afterwards cells recognize inflammatory
response
• The effect of the injury or biomaterial
produces chemical factors that mediate
vascular and cellular reponses
• Followed by thrombosis and or clot formation
(hematocompatibility)
 Provisional Matrix
• Results from injury to vascularized tissue
• Consists of fibrin, inflammatory products,
activated platelets and endothelial cells.
• Components of the matrix initiate the
reorganization and repair process
 Provisional Matrix
• Provides structural and biochemical
components for wound healing
• The complex 3D structure of fibrin network
provides a substrate for cell-adhesion and
migration
• Biomaterial and adsorbed proteins modulate
material-cell interaction
 Inflammation
• Neutrophils are first present in the
inflammatory response
• Their presence is effected by:
– The cells themselves are short-lived ad quickly
disintegrate
– Their emigration duration is short
– Specific chemotactic factors are activated early in
the inflammation process
 Inflammation
• Monocytes replace neutrophils then differentiate
into macrophages
• The duration and the intensity of the
inflammation or the wound healing response is
dependent on the size, shape, chemical and
physical property of the implant
• It is a measure of biocompatibility
• Chemical released from plasma, cells, and injured
tissue mediate the inflammatory response
Response Sequence
 Acute Inflammation
• Short duration from minutes to days
• Chatacterized by edema and the emigration of
leukocytes especially neutrophils
• Neutrophils are polymorphonuclear leukocytes
• Emigration assisted by adhesion molecules on
both WBC and endothelial cells
• The expression of these molecules is affected by
the imflammatory response
• WBC migration controlled by chemotaxis
 Acute Inflammation
• Specific receptors on the leukocytes detect
chemotactic agents, they also control
transmigration of WBC across the vessels
endothelium the activation of leukocytes
• After localization of WBCs phagocytosis and the
release of enzymes take place
• Phagocytosis:
– Recognition &Neutrophil attachment
– Engulfment
– Killing and Degradation
 Acute Inflammation
• Phagocytosis rare for biomaterials, why?
• Recognition is speeded up by the presence of
opsonins
• Frustrated phagocytosis
• Neurtrophils adherent to nonphagocytosable
surfaces release enzymes
• Larger particles in the biomaterial induce
greater enzyme release
Acute Inflammation
 Chronic Inflammation
• Characterized by the presence of macrophages,
monocytes, and lymphocytes
• Proliferation of blood vessels and connective
tissue
• Could be either caused by the nature of the
biomaterial or by motion in the implant
• Short duration and confined to the implant site
• Lymphocytes and plasma are related to the
immune reaction and are signals for a chronic
response whereas granulation tissue formation is
the normal response
 Chronic Inflammation
• Two sources for response:
– Specialized immune cells in specific tissues
– Components released from the implant (corrosion and
degradation products, and wear debris)
• Macrophages produce most biological active
products including chemotactic factors, and
growth factors.
• Growth factors have roles in fibroblasts growth,
blood vessel growth, and epithelial cell
regeneration.
Chronic Inflammation
 Granulation Tissue
• Fibroblasts and vascular endothelial cells in the
implant site proliferate and form granulation
tissue
• Seen 3-5 days after implantation
• Angiogenesis includes proliferation, maturation,
and organization of endothelial cells
• At the beginning of the process proteoglycans
dominate then type III collagen dominates to
form the fibrous capsule
Granulation Tissue
 Granulation Tissue
• Wound- healing response is dependent on the
degree of injury or defect caused by implant
• Types of wound healing:
– Primary union/ first intention: with stitches and
minimum loss of tissue
– Secondary union/ second intention: large tissue
defect. Usually end up with scar formation or
fibrosis
Foreign Body Giant Cells
 Foreign Body Reaction
• Composed of foreign body giant cells and
components of granulation tissue.
• Reaction dependent on the form and
topography of the implant
• Smooth surfaces have a reaction of one layer
of macrophages one to two cells in thickness
• Rough surfaces have a reaction of
macrophages and foreign body giant cells
Foreign Body Reaction
Foreign Body Reaction
 Foreign Body Reaction
• If a material is biocompatible the reaction
maybe controlled by controlling:
– The surface properties of the implant
– The form of the implant
– The surface area to volume ratio
• Fibrous encapsulation surrounds the
biomaterial with its interfacial body reaction
to isolate them from the rest of the body
Event Sequence
Fibrosis and Fibrous Encapsulation
• Last response to biomaterials
• Repair of the implant site can be one of two:
– Regeneration
– Replacement with fibrous capsule
• Dependent on:
– Proliferative capacity of cells in the tissue (labile,
stable/expanding, permanent/static)
– Retention of the framework
Fibrosis and Fibrous Encapsulation
Fibrosis and Fibrous Encapsulation
Fibrosis and Fibrous Encapsulation
• Cellular adaptations:
– Atrophy
– Hypertrophy
– Hyperplasia
– Metaplasia
– Phenotypic change
– Protein overexpression
Fibrosis and Fibrous Encapsulation
• Local factors:
– Site of implantation
– Adequacy of blood supply
– Potential for infection
• Systematic factors:
– Nutrition
– Hematologic derangements
– Glucocortical steroids
– Preexisting diseases
– Infection
 Bottomline
• Response CANNOT be predicted