BIOMATERIALS ENT 311/4 LECTURE 6 Tissue Reaction to Biomaterials Prepared by: Nur Farahiyah Binti Mohammad Date: 7 th August

Teaching Plan Objective Describe, discuss and illustrate inflammation, wound healing, foreign body reaction, blood material interaction and tumorgenesisi. DELIVERY MODE Lecture Tutorial Supplement reading LEVEL OF COMPLEXITY Knowledge Repetition Application COURSE OUTCOME COVERED Ability to explain and illustrate tissue reaction to biomaterials

1.0INTRODUCTION  Biomaterials and medical devices now commonly used as prostheses in cardiovascular, orthopaedic, dental, in interventions such as angioplasty (stent) and haemodialysis (membrane), in surgical sutures and as controllers drug release devices.  Most implant serve their recipients well for extended periods by alleviating the condition for which they were implanted.

However, some implants or biomaterials ultimately develop complication.However, some implants or biomaterials ultimately develop complication. –Undesirable interaction of the patient with the device, or –Adverse interaction of the device with the patient This will lead to device failure and thereby may cause harm or death of patient.This will lead to device failure and thereby may cause harm or death of patient. 1.0INTRODUCTION

2.0EFFECT OF MATERIAL ON HOST TISSUE The main cellular host response to injury are:The main cellular host response to injury are: 2.1Inflammation 2.2Wound healing 2.3Foreign body reaction

INJURY HEMOSTASIS INFLAMMATION PROLIFERATION (granulation tissue) FOREIGN BODY GIANT CELL FORMATION REMODELLING Acute Inflammation Chronic Inflammation SCAR TISSUE or FIBROUS CAPSULE DEVELOPMENT Sequence of host reaction following implantation of medical devices or biomaterial PROLIFERATION (granulation tissue)

2.1INFLAMMATION Defined as the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants.Defined as the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation serve to contain, neutralize, dilute or wall off injuries agent or process.Inflammation serve to contain, neutralize, dilute or wall off injuries agent or process.

2.1INFLAMMATION It sets into motion series of events that may heal and reconstitute the implant site through replacement of the injures tissue br regeneration of native parenchymal cells, formation scar tissue or combination of this two process.It sets into motion series of events that may heal and reconstitute the implant site through replacement of the injures tissue br regeneration of native parenchymal cells, formation scar tissue or combination of this two process.

2.1INFLAMMATION ACUTE INFLAMMATION An immediate response to tissue injury.An immediate response to tissue injury. Occur in the first minute to days after the injury.Occur in the first minute to days after the injury. The four Cardinal signs or Clinical signs of inflammation are:The four Cardinal signs or Clinical signs of inflammation are: 1.Rubor (redness) 2.Tumor (swelling) 3.Calore (tissue heating) 4.Dolore (pain)

2.1.1ACUTE INFLAMMATION Redness is caused by dilation of nearby blood vessel in response to a mediators called prostaglandin.Redness is caused by dilation of nearby blood vessel in response to a mediators called prostaglandin. Swelling is caused by the leakage of plasma proteins into the surrounding (interstitial) space through the leaky vessel.Swelling is caused by the leakage of plasma proteins into the surrounding (interstitial) space through the leaky vessel. Local heat is caused by increased blood flow and higher metabolic rates.Local heat is caused by increased blood flow and higher metabolic rates. Pain associated with inflammatory response is a by-product of the release of certain substances called kinins from the blood clotting cascade.Pain associated with inflammatory response is a by-product of the release of certain substances called kinins from the blood clotting cascade.

Now the cellular part of the response occurs.Now the cellular part of the response occurs. The white blood cells that infiltrate the wound first are phagocytic neutrophils (from blood stream).The white blood cells that infiltrate the wound first are phagocytic neutrophils (from blood stream). Neutrophils engulf bacteria, debris and foreign organism.Neutrophils engulf bacteria, debris and foreign organism. Due to signals realesed by the neutrophils, about 5 to 6 hours after the inflammatory response begins, monocytes arrive at the injury site.Due to signals realesed by the neutrophils, about 5 to 6 hours after the inflammatory response begins, monocytes arrive at the injury site.

2.1.1ACUTE INFLAMMATION Neutrophils and monocytes start to enlarge to form tissue macrophages.Neutrophils and monocytes start to enlarge to form tissue macrophages. Macrophages maturation can take up to 8 hours and involves swelling of the cell and formation of large quantity of lysosomes.Macrophages maturation can take up to 8 hours and involves swelling of the cell and formation of large quantity of lysosomes. The function of macrophage are similar to that of the neutrophil, although macrophages have greater and more sustainable killing capacities.The function of macrophage are similar to that of the neutrophil, although macrophages have greater and more sustainable killing capacities.

2.1.1ACUTE INFLAMMATION Macrophages and trapped platelets secretes factors that promotes angiogenesis, promotes chemotaxis and mitosis for surrounding fibroblast.Macrophages and trapped platelets secretes factors that promotes angiogenesis, promotes chemotaxis and mitosis for surrounding fibroblast. Finally, lymphocyte infiltrate the wound.Finally, lymphocyte infiltrate the wound.

2.1.2CHRONIC INFLAMMATION Chronic inflammation is a pathological condition characterized by concurrent active inflammation, tissue destruction, and attempts at repair.Chronic inflammation is a pathological condition characterized by concurrent active inflammation, tissue destruction, and attempts at repair. Chronic inflammation is not characterized by the classic signs of acute inflammation.Chronic inflammation is not characterized by the classic signs of acute inflammation.

Instead, chronically inflamed tissue is characterized by:Instead, chronically inflamed tissue is characterized by: –the infiltration of mononuclear immune cells (monocytes, macrophages, lymphocytes, and plasm cells), –tissue destruction –Proliferation of blood vessels and connective tissue (fibrosis) 2.1.2CHRONIC INFLAMMATION

In chronically inflamed tissue the stimulus is persistent, and therefore recruitment of monocytes is maintained, existing macrophages are tethered in place, and proliferation of macrophages is stimulated.In chronically inflamed tissue the stimulus is persistent, and therefore recruitment of monocytes is maintained, existing macrophages are tethered in place, and proliferation of macrophages is stimulated.

Comparison between acute and chronic inflammation: AcuteChronic Causative agent Pathogens, injured tissues Persistent acute inflammation due to non-degradable pathogens, persistent foreign bodies, or autoimmune reactions Major cells involved Neutrophils, mononuclear cells (monocytes, macrophages) Mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts Primary mediators Vasoactive amines, eicosanoids IFN- γ and other cytokines, growth factors, reactive oxygen species, hydrolytic enzymes OnsetImmediateDelayed DurationFew daysUp to many months, or years Outcomes Healing, abscess formation, chronic inflammation Tissue destruction, fibrosis

2.2WOUND HEALING RESPONSE Four stages: 1.Hemostasis (seconds to minute) 2.Inflammation (minutes to day) 3.Proliferative phase (days to week) 4.Remodelling phase (week to year)

INJURY HEMOSTASIS INFLAMMATION (Acute Inflammation) PROLIFERATION (granulation tissue) REMODELLING SCAR TISSUE or FIBROUS CAPSULE DEVELOPMENT WOUND HEALING RESPONSE

2.2WOUND HEALING RESPONSE

Injury Constriction of leaking vessel to reduce the flow of blood through the opening in a torn or severed vessel. Collagen in in connective tissue attract plat lets, which form a platelet plug to fill the gap in a broken vessel. Formation of fibrin clot (serve as a provisional matrix for further healing) Platelets are trapped in the provisional matrix and release growth factor HEMOSTASIS Second to minute Neutrophils and macrophages engulf bacteria Macrophages and trapped platelets secretes factors that promotes angiogenesis, promotes chemotaxis and mitosis for surrounding fibroblast. Lymphocyte infiltrate the wound INFLAMMATION Minute to day Neutrophils & monocytes (that transform into macrophages) attracted into the wound

Fibroblasts cells and epithelial cells start to reconstruct the tissue. Fibroblast cells form granulation tissue which also contains macrophages, some newly formed blood vessels, and a more complex protein matrix. At the wound end, the epithelial cells flatten, divide, and migrate in order to fill the gap. This process will continues until epithelial cell into contact with one another Tissue remodels Collagen fibre reorganized, remodelled and mature, gains tensile strength. Collagen fibre, proteoglycan and fibre actins rearrange and redistributed. Scar become less cellular and gain tensile strength. However, this tissue always risk for breakdown because tensile strength is less than uninjured skin. Proliferative days to week Remodelling Week to year