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Wound Healing- Part I

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Why Study Wound Healing?
50 million surgical procedures performed each year in
the US alone;
Recovery from these procedures conservatively requires
250 million patient days in lost productivity and billions of
dollars in lost or supplemental earnings;
Despite the technical advances, complications resulting
from surgery has not declined over the past 50 years;
The wound healing response affects implant
performance:
Blocks flow in catheters, cannulas and infusion pumps;
Forms impedance barriers around electrodes, drug delivery systems
Degrades polymeric materials; and,
Thrombus formation blocks dialysis membranes and vascular
grafts,etc.

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Wound Healing
The process of repair
A cascade of events that involves the interaction of
various cellular and molecular components that act in
synchrony to effect wound closure by forming new
tissue.
The process can be understood as progressing through
multiple stages, but realistically takes place as a
continuum.
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Normal Tissue
Multi-cellular
Three-dimensional structures
Extracellular Matrix
Multi-functional
Takes cues from the
environment
Interface with surroundings
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Tissue Injury
Results in a variety of cellular responses including:
Necrosis (death by extrinsic means)
Apoptosis (death by suicide)
Atrophy (decrease in cell size and/ or function)
Hypertrophy (increase in cell size)
Hyperplasia (increase in cell numbers)
Metaplasia (change in cell type)
Change in phenotype (change in the type and/or
amount of protein characteristic of a particular cell
type)
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Different Tissues have
Different Capacities to Heal
Regenerative capacity varies:
High capacity
epithelial, lymphoid, hematopoietic, mesenchymal
tissues (cell types include fibroblasts, smooth
muscle cells, osteoblasts, chrondrocytes, and
endonthelial cells)
Highly vascularized
Low capacity
Nerve, muscle (skeletal and cardiac), cartilage
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The Biology of Wound Healing -
Vascularized Tissue
Most of what we know has come from studies in skin of
adult mammalian species;
In general, wound healing proceeds slower and with
more scarring as a function of increasing age


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From a Bioengineering
Perspective
A series of time-dependent reactions that integrate into
an expected outcome of resolution or scar formation;
Each event follows a predictable temporal pattern;
Perturbations to any event predictably lengthen the
amount of time required for normal healing;
These may include the size of the wound, the amount of
contamination or infection, the degree of vascularization
of the tissue, presence of a foreign body, and the
general health & age of the patient;
The process can be conceptualized in terms of a set of
processes whose mathematical trajectory can be
measured and modeled over time.
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Sequence of Events Following
Device Implantation:
Injury
acute inflammation
chronic inflammation
granulation tissue
foreign body reaction
fibrous encapsulation

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Sequence of local events following
implantation
Injury
Injection, implantation
Acute inflammation
Polymorphonuclear leukocytes
Chronic inflammation
Monocytes and lymphocytes
Granulation tissue
Fibroblasts and new blood capillaries
Foreign body reaction
Macrophages and FBGCs at the material-tissue interface
Fibrosis
Fibrous capsule