Host Response to Material Implantation

1. Host Response to Material Implantation • Implantation of a biomaterial is an invasive procedure that initiates a series of events whose outcome ultimately determine the biocompatibility of the material. • OBJECTIVES • to outline the normal wound healing response • to outline the change in this response in the presence of a biomaterial CHEE 340

2. Normal Wound Healing • wound healing is a dynamic cascade of events initiated by injury • it may be divided into phases characterized by both cellular population and cellular function • blood clotting • inflammation • cellular invasion and remodeling CHEE 340

3. Host Defence • The body is under constant attack by microorganisms in the environment. • pathogen : an infectious agent that causes disease • Infectious disease occurs when a microorganism succeeds in evading or overwhelming host defenses to establish a local site of infection and replication. In order for a pathogen to enter the body it must first overcome the epithelium and then the innate immune response. CHEE 340

4. First Line of Defence • Epithelial Tissue • covers the whole surface of the body • made up of closely packed cells • can be divided into simple or stratified • interior epithelium covered with a mucus layer CHEE 872

5. Clotting or Thrombosis • blood coagulation or clotting is the blood response to damaged blood vessels • objective is to form a patch that isolates the leak and stops blood loss CHEE 340

6. Coagulation Pathways CHEE 340

7. Intravascular Cells • white blood cells Granulocytes neutrophil eosinophil basophil lymphocyte monocyte CHEE 340

8. Innate Immune response • If a pathogen breaches the epithelium, • then the innate immune response begins. • The cells of the immune system determine • “self” from “non-self” by recognizing molecules on the microbe surface. • Macrophages and dendritic cells are immune cells (phagocytes) that reside within the tissue. Neutrophils are phagocytes that reside in the blood but can extravasate into tissue during inflammation. • There are circulating proteins, called complement, that either kill microbes or mark them for effective phagocytization. CHEE 340

9. Phagocytosis Phagocytosis: Engulfing and degradation or digestion of fragments of tissue or material long membrane evaginations, called pseudopodia. Ingestion forming a "phagosome," which moves toward the lysosome. Fusion of the lysosome and phagosome (phagolysosome), releasing lysosomal enzymes Digestion of the ingested material. Release of digestion products from the cell. CHEE 340

10. Phagocytosis Movie CHEE 340

11. Inflammatory Response • Pathogen recognition and tissue damage begin an inflammation response. This is characterized by : • swelling • pain • redness • heat • Inflammation allows for neutrophil and plasma protein extravasation. Both of these effects aids the immune response. CHEE 340

12. Diapedesis Movie CHEE 340

13. Leukocyte Invasion at Wound Site CHEE 340

14. Inflammation from: AJ Singer, RAF Clark, New England J Med 341 (1999) 738 CHEE 872

15. Granulation Tissue Deposition - Remodeling • Due to death of cells following injury, and their removal, there is a local decreased tissue mass • fibroblasts and vascular endothelial cells are recruited to site CHEE 340

16. Angiogenesis CHEE 872

17. Wound Healing CHEE 340

18. Foreign Body Reaction • The presence of the implant changes the healing response, and this is called the Foreign Body Reaction. • FBR consists of: • protein adsorption • macrophages • multinucleated foreign body giant cells • fibroblasts • angiogenesis CHEE 340

19. Components of Plasma CHEE 340

20. Proteins • are polyamides, composed of amino acids CHEE 340

21. Soluble Proteins (A) A space-filling model of myoglobin with hydrophobic amino acids shown in yellow, charged amino acids shown in blue, and others shown in white. The surface of the molecule has many charged amino acids, as well as some hydrophobic amino acids. (B) A cross-sectional view shows that mostly hydrophobic amino acids are found on the inside of the structure, whereas the charged amino acids are found on the protein surface. albumin CHEE 340

22. Protein Adsorption B. Amsden

23. Protein Adsorption and Cell Response

24. Vroman Effect From: An Introduction to Tissue-Biomaterial Interactions, Wiley, 2002. CHEE 340

25. Foreign Body Response • continuing presence of an implant may result in the attainment of a final steady-state condition called resolution • there are 3 possible outcomes for the implant : • resorption • integration • encapsulation (fibrosis) CHEE 340

26. Wound Healing in Presence of Biomaterial • protein adsorption mediates neutrophil and macrophage response Den Dunnen et al. J Biomed Mater Res 36 (1997) 337 CHEE 340

27. Frustrated Phagocytosis CHEE 340

28. Example in vivo response to implanted biodegradable elastomer CHEE 872

29. Experimental Results poly(trimethylene carbonate) elastomer implanted s.c. in rats CHEE 872

30. Cell Regeneration After Injury • Possible outcomes for the injured tissue: • replacement of injured tissue with parenchymal cells of the same type • replacement by connective tissue that constitutes the fibrous capsule • The regeneration of cells in the body is tightly controlled • There are essentially 3 categories of cell populations • Renewing or labile • Expanding or stable • Static or permanent CHEE 340