Wound Healing- Part I

1. Wound Healing- Part I

2. 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.

3. 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.

4. Normal Tissue • Multi-cellular • Three-dimensional structures • Extracellular Matrix • Multi-functional • Takes cues from the environment • Interface with surroundings

5. 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)

6. 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

7. 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

8. 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.

9. Sequence of Events Following Device Implantation: • Injury • acute inflammation • chronic inflammation • granulation tissue • foreign body reaction • fibrous encapsulation

10. 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