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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