The document summarizes host reactions to biomaterials. It discusses mechanical and biological effects of the host on implants as well as local and systematic effects of implants on the host. It then describes the local events following implantation, including injury, acute inflammation, chronic inflammation, granulation tissue formation, foreign body reaction, and fibrosis or fibrous encapsulation of the implant.

1. Host Reactions to Biomaterials

2. Introduction All implants interact with the biological environment around them Effects go both ways “Effects of tissue on the implant and vice versa”

3. Mechanical Effects of Host on Implant Abrasive wear Fatigue Stress-corrosion cracking Corrosion Degeneration and dissolution

4. Biological Effects of Host on Implants Absorption of substances from tissue Enzymatic degradation Calcification

5. Local Effect of Implant on Host Blood material interaction Toxicity Modification of normal healing Infection Tumorigenesis Protein absorption, coagulation, fibrinolysis, platelet adhesion, complement activation, leukocyte adhesion, hemolysis Encapsulation, foreign body reaction, pannus formation

6. Systematic Effect of Implant on Host Embolization Hypersensitivity Elevation of implant elements in blood Lymphatic particle transport

7. Local Events Following Implantations Injury Acute inflammation Chronic inflammation Granulation tissue Foreign body reaction Fibrosis

8. Inflammation The reaction of vascularized living tissue to local injury Goals are: To reduce the agent or process causing injury To start off healing process by regenerating parenchymal cells and the formation of fibroblastic scar tissue

9. Inflammation After injury there are changes in vascular flow, caliber, and permeability for exudation “Exudation: fluid, protein, and blood cells escape from the vascular system into injured tissue” Afterwards cells recognize inflammatory response Followed by thrombosis and or clot formation (hematocompatibility)

10. Inflammation Neutrophils are first present in the inflammatory response Their presence is effected by: The cells themselves are short-lived ad quickly disintegrate Their emigration duration is short Specific chemotactic factors are activated early in the inflammation process

11. Inflammation Monocytes replace neutrophils then differentiate into into macrophages The duration and the intensity of the inflammation or the wound healing response is dependent on the size, shape, chemical and physical property of the implant It is a measure of biocompatibility Chemical released from plasma, cells, and injured tissue mediate the inflammatory response

12. Response Sequence

13. Acute Inflammation Short duration from minutes to days Chatacterized by the emigration of leukocytes especially neutrophils Emigration assisted by adhesion molecules on both WBC and endothelial cells The expression of these molecules is affected by the imflammatory response WBC migration controlled by chemotaxis

14. Acute Inflammation Specific receptors on the leukocytes detect chemotactic agents, they also control the activation of leukocytes After localization of WBCs phagocytosis and the release of enzymes take place Phagocytosis: Recognition &Neutrophil attachment Engulfment Killing and Degradation

15. Acute Inflammation Phagocytosis rare for biomaterials, why? Disparity in size Recognition is speeded up by the presence of opsonins “Opsonins naturally occurring serum factors including immunoglubulins IgG and complement activated gragment C3b and the adsorb to biomaterials” Frustrated phagocytosis Neurtrophils adherent to nonphagocytosable surfaces release enzymes “ Enzymes are released by direct extrusion or exocytosis” Larger particles in the biomaterial induce greater enzyme release

16. Chronic Inflammation Characterized by the presence of macrophages, monocytes, and lymphocytes Proliferation of blood vessels and connective tissue Could be either caused by the nature of the biomaterial or by motion in the implant Lymphocytes and plasma are related to the immune reaction

17. Chronic Inflammation Two sources for response: Specialized immune cells in specific tissues Components released from the implant (corrosion and degradation products, and wear debris) Macrophages produce most biologicall active products including chemotactic factors, and growth factors. “Growth factors stimulate cell production and migration, differentiation, and tissue remodeling” Growth factors have roles in fibroblasts growth, blood vessel growth, and epithelial cell regeneration.

18. Granulation Tissue Fibroblasts and vascular endothelial cells in the implant site proliferate and form granulation tissue “Granulation tissue from the pink soft granular appearance on the surface of healing tissue” Seen 3-5 days after implantation Angiogenesis small blood vessel formation Angiogenesis includes proliferation, maturation, and organization of endothelial cells At the beginning of the process proteoglycans dominate then type III collagen dominates

19. Granulation Tissue Types of wound healing: Primary union/ first intention: with stitches and minimum loss of tissue Secondary union/ second intention: large tissue defect. Usually end up with scar formation or fibrosis

20. Foreign Body Reaction Foreign body giant cells are formed by the fusion of monocytes and macrophages to phagocytose the material Composed of foreign body giant cells and components of granulation tissue. Reaction dependent on the form and topography of the implant Smooth surfaces have a reaction of one layer of macrophages one to two cells in thickness Rough surfaces have a reaction of macrophages and foreign body giant cells

21. Foreign Body Reaction If a material is biocompatible the reaction maybe controlled by controlling: The surface properties of the implant The form of the implant The surface area to volume ratio Smooth surfaces will have fibrosis while porous materials will have a large amount of macrophages and foreign body giant cells Fibrous encapsulation surrounds the biomaterial with its interfacial body reaction to isolate them from the rest of the body

22. Fibrosis and Fibrous Encapsulation Last response to biomaterials Repair of the implant site can be one of two: Regeneration: replacement of the injured tissue with parenchymal cells of the same type Replacement with fibrous capsule “Fibrous capsule: connective tissue” Dependent on: Proliferative capacity of cells in the tissue (labile, stable/expanding, permanent/static) Retention of the framework

23. Fibrosis and Fibrous Encapsulation Cellular adaptations: Atrophy Hypertrophy Hyperplasia Metaplasia Phenotypic change Protein overexpression

24. Fibrosis and Fibrous Encapsulation Local factors: Site of implantation Adequacy of blood supply Potential for infection Systematic factors: Nutrition Hematologic derangements Glucocortical steroids Preexisting diseases Infection

25. Bottomline Response CANNOT be predicted