Wound Healing- Part I

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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