inflammation and wound healing
DESCRIPTION
biomaterialsTRANSCRIPT
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1 8 April 2015
Inflammation and wound healing Yashveer Singh, PhD
Department of Chemistry
CYL458: Biomaterials
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Biomaterial tissue interactions
Wound healing responses under
normal injury and
implantation
Anderson, Semin Immunol 2008, 20, 86
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3 BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
Biomaterial tissue interactions
The wound healing processes has following phases
Inflammatory (Acute and Chronic) Proliferative/Repair Remodeling/maturation
PMN: polymorphonuclear leukocytes or neutrophils
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Leukocytes
Granulocytes: cells with granular appearance, are subdivided into
neutrophils, eosinophils, and basophils. Function is to phagocytose
foreign invaders and aid in inflammatory responses
Monocytes: Cells with no nuclei, differentiate into macrophages. Have large phagocytosis capability and play a central role in
inflammatory response
Lymphocytes / plasma cells: T and B cells, part of acquired immune response
Megakaryocytes: Found in bone marrow. It fragments to form platelets
Granulocytes live for 4-5 days, whereas macrophages may survive for months to year
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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5 Wikipedia
Leukocytes
Granulocytes Monocytes
Lymphocytes Megakaryocytes Platelets
Leukocytes
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6 Lodish, Molecular Cell Biology, WH Freeman
Phagocytosis
Three common mechanism of
phagocytosis
shown:
phagocytosis;
endocytosis; and
autophagy
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Acute inflammation
During inflammation, neutrophils predominate during the first few days of injuries, which are short-lived and disappear after 24-48 hours
Neutrophils emigration is of short duration and chemotactic factors are activated early in the inflammatory response
The size, shape, and chemical, and physical properties of biomaterials will influence the above process. While injury initiates inflammatory
response, the chemicals are released from plasma, cells, and injured tissue
to mediate the response
Neutrophils are replaced by monocytes, which differentiates into macrophages and these cells are very long lived (months). Monocyte
migration continues for days to weeks
Mast cells degranulate and release histamine (recruitment of phagocytosis) release along with interleukins (IL 4 and 13, induces foreign
body reaction) and fibrinogen is adsorbed
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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There is exudation of fluids and plasma proteins and emigration of leukocytes (primarily neutrophils), from blood vessels to
perivascular tissues and then to the injury site
Migration is assisted by adhesion molecules present on leukocytes and endothelial surfaces, which is induced, enhanced or altered by
inflammatory agents and chemical mediators
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
Acute inflammation
Layer of neutrophils
adhering to the inner
surface of the blood vessel
bme.ucdavis.edu
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Following localization at the injury site, phagocytosis and release of enzymes occurs. Neutrophils phagocytose microorganism and foreign
materials. Phagocytosis has following steps- injurious agent undergo
recognition and neutrophil attachment, engulfment, and killing or
degradation
In general, biomaterials are not phagocytosed because of disparity in size
The process of recognition and attachment will be more if the injurious agent is coated with serum factor called opsonin (IgG and
complement-activated fragment C3b)
Since phagocytosis cannot occur, leukocytes degradation products are released (frustrated phagocytosis)
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
Acute inflammation
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Characterized by the presence of macrophages, monocytes, and lymphocytes with proliferation of blood vessels and connective
tissue
Persistent inflammatory stimuli lead to chronic inflammation, caused by the chemical and physical property of the biomaterial
and motion in the implant site by the biomaterial
Monocytes differentiates into macrophages, and belong to mononuclear phagocytic system (MPS), also termed as
reticuloendothelial system (RES)
Macrophages release neutral proteases, chemotactic factors, arachidonic acid metabolites, reactive oxygen metabolites,
complement components, coagulation factors, growth promoting
factors, and cytokines
Usually confined to the implant site
Chronic inflammation
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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11 http://courses.washington.edu/conj/inflammation/chronicinflam.htm
The figure shows macrophages distended with lipid from broken down myelin at the site of necrotic tissue due to a blocked blood
vessel in the brain
Persistence of chronic response beyond 2-3 weeks time will indicate infection
Chronic inflammation
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Within a day of implantation, healing
responses are initiated by the action of
monocytes and macrophages
Fibroblast and vascular endothelial cells proliferate at the site to form granulation
tissue
The new small blood vessels are formed by budding or sprouting of preexisting vessels
(neovascularization or angiogenesis)
Fibroblasts proliferates in granulation tissue and synthesize collagen and proteoglycans,
which causes wound contraction
Granulation tissue
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
Granulation tissue
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Formation of granulation tissue by proliferation of blood
vessels and fibroblast
Granulation tissue
edoc.hu-berlin.de
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Wound healing by primary union or first intention: Healing of clean surgical incisions, where wound edges are approximated by surgical
sutures. Healing occurs without bacterial contamination and with minimum
tissue loss
Wound healing by secondary union or second intention: Healing of large tissue defects. Regeneration of parenchymal cells is unable to
completely reconstitute lost tissue and much larger amount of granulation
tissue are formed, leading to scar formation (fibrosis)
Granulation tissue
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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Granulation tissue
Google images
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The foreign body reaction to implants involve formation of foreign
body giant cells and component of granulation tissue (macrophages,
fibroblasts, and capillaries)
Macrophages adhere to the implant surface using integrin receptors. The macrophages then undergo cytoskeleton remodeling to spread
over the implant surface. Finally, macrophages fuses to form foreign
body giant cells. IL-4 plays a key role in fusion
The macrophages and foreign body giant cells persists at the tissue-biomaterial interface for the life of implant
Foreign body reaction
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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Foreign body reaction
SEM images of an Elasthane 80A
polyurethane surface
(in vivo)
Monocytes adhere to surface (0 days, A),
monocyte differentiate
into macrophage (3
days, B), macrophages
undergoing fusion (7
days, C), foreign body
giant cells formed (14
days, D)
Anderson, Semin Immunol 2008, 20, 86
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Foreign body reaction
Topology and form of implant influence this process. Smooth and
flat surfaces (breast prostheses) have macrophages 1-2 cells thick,
and rough surfaces (PTFE vascular prostheses) have macrophages
and foreign body giant cells at the surface
High surface-to-volume implants (fabrics/porous materials) have higher ratios of macrophages and giant cells than the smooth surface
implant
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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When the foreign material is not phagocytosed or removed, the implant is encapsulated in a dense layer of connective tissue
(fibrous capsule) to isolate it from the surrounding tissues and
shield it from immune system
Repair of implant sites involve two distinct processes: regeneration of injured tissue by parenchymal cells of the same
type or replacement by connective tissue that constitute the fibrous
capsule
It depends on (i) proliferative capacity of cells in the tissue or organ receiving the implant and extent of injury as it related to
implants; and (ii) persistence of the tissue framework at the implant
site
Fibrosis/fibrous encapsulation
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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Cells are classified into three groups based on regenerative
capacity:
Labile cells, which continue to proliferate (epithelial and lymphoid
cells)
Stable (expanding) cells, which retain the capacity but do not
replicate (parenchymal cells of liver, kidney, pancreas)
Permanent (static) cells, which do not reproduce after birth (nerve,
skeletal muscle, and cardiac muscle cells)
Tissues composed of permanent cells most likely undergo fibrosis (fibrous capsule formation) and those composed of stable or labile
cells may undergo fibrosis or restitution of normal tissue
vasculature
Fibrosis/fibrous encapsulation
BT Ratner, Biomaterials Science: An Introduction to Materials in Medicine, CRC Press
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Fibrosis/fibrous encapsulation
The C-implant was removed before
histological studies. Fibrous
encapsulation of bone marrow part of
C-implant is shown. e-kjo.org
A normal and encapsulated breast implant.
www.cosmeticbreastsurgeon.co.uk
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Fibrosis/fibrous encapsulation
www.nature.com