biomaterials ent 311/4 lecture 6 tissue reaction to biomaterials prepared by: nur farahiyah binti...

BIOMATERIALSBIOMATERIALSENT 311/4ENT 311/4

LECTURE 6LECTURE 6Tissue Reaction to Tissue Reaction to BiomaterialsBiomaterials

Prepared by: Nur Farahiyah Binti Mohammad

Date: 7th August 2008

Email : [email protected]

Teaching PlanTeaching Plan Objective

Describe, discuss and illustrate inflammation, wound healing, foreign body reaction, blood material interaction and tumorgenesisi.

DELIVERYMODE

•Lecture•Tutorial•Supplement reading

LEVEL OF COMPLEXITY

•Knowledge•Repetition•Application

COURSE OUTCOMECOVERED

•Ability to explain and illustrate tissue reaction to biomaterials

1.01.0INTRODUCTIONINTRODUCTION

Biomaterials and medical devices now Biomaterials and medical devices now commonly used as prostheses in commonly used as prostheses in cardiovascular, orthopaedic, dental, in cardiovascular, orthopaedic, dental, in interventions such as angioplasty (stent) interventions such as angioplasty (stent) and haemodialysis (membrane), in and haemodialysis (membrane), in surgical sutures and as controllers drug surgical sutures and as controllers drug release devices. release devices.

Most implant serve their recipients well for Most implant serve their recipients well for extended periods by alleviatingextended periods by alleviating the the condition for which they were implanted.condition for which they were implanted.

• However, some implants or However, some implants or biomaterials ultimately develop biomaterials ultimately develop complication. complication. – Undesirable interaction of the patient with Undesirable interaction of the patient with

the device, or the device, or

– Adverse interaction of the device with the Adverse interaction of the device with the patientpatient

• This will lead to device failure and This will lead to device failure and thereby may cause harm or death of thereby may cause harm or death of patient.patient.

1.01.0INTRODUCTIONINTRODUCTION

2.02.0 EFFECT OF MATERIAL ON EFFECT OF MATERIAL ON HOST TISSUEHOST TISSUE

• The main cellular host response to The main cellular host response to injury are: injury are: 2.12.1 InflammationInflammation

2.22.2 Wound healingWound healing

2.32.3 Foreign body reactionForeign 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 Sequence of host reaction host reaction following following implantation of implantation of medical devices medical devices or biomaterialor biomaterial


2.12.1INFLAMMATIONINFLAMMATION

• Defined as the complex biological Defined as the complex biological response of vascular tissues to response of vascular tissues to harmful stimuli, such as pathogens, harmful stimuli, such as pathogens, damaged cells, or irritants. damaged cells, or irritants.

• Inflammation serve to contain, Inflammation serve to contain, neutralize, dilute or wall off injuries neutralize, dilute or wall off injuries agent or process. agent or process.

2.12.1INFLAMMATIONINFLAMMATION

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

2.12.1INFLAMMATIONINFLAMMATION2.1.1 ACUTE INFLAMMATION2.1.1 ACUTE INFLAMMATION

•An immediate response to tissue injury.An immediate response to tissue injury.•Occur in the first minute to days after the Occur in the first minute to days after the injury. injury.

•The four The four Cardinal signsCardinal signs or Clinical signs of or Clinical signs of inflammation are:inflammation are:

1.1. Rubor (redness)Rubor (redness)

2.2. Tumor (swelling)Tumor (swelling)

3.3. Calore (tissue heating)Calore (tissue heating)

4.4. Dolore (pain) Dolore (pain)

2.1.12.1.1 ACUTE ACUTE INFLAMMATIONINFLAMMATION

• RednessRedness is caused by dilation of nearby is caused by dilation of nearby blood vessel in response to a mediators blood vessel in response to a mediators called prostaglandin.called prostaglandin.

• SwellingSwelling is caused by the leakage of is caused by the leakage of plasma proteins into the surrounding plasma proteins into the surrounding (interstitial) space through the leaky vessel.(interstitial) space through the leaky vessel.

• Local heatLocal heat is caused by increased blood is caused by increased blood flow and higher metabolic rates.flow and higher metabolic rates.

• Pain Pain associated with inflammatory response associated with inflammatory response is a by-product of the release of certain is a by-product of the release of certain substances called kinins from the blood substances called kinins from the blood clotting cascade. clotting cascade.

• Now the cellular part of the response Now the cellular part of the response occurs.occurs.

• The white blood cells that infiltrate The white blood cells that infiltrate the wound first are phagocytic the wound first are phagocytic neutrophils (from blood stream).neutrophils (from blood stream).

• Neutrophils engulf bacteria, debris Neutrophils engulf bacteria, debris and foreign organism.and foreign organism.

• Due to signals realesed by the Due to signals realesed by the neutrophils, about 5 to 6 hours after neutrophils, about 5 to 6 hours after the inflammatory response begins, the inflammatory response begins, monocytes arrive at the injury site.monocytes arrive at the injury site.

2.1.12.1.1 ACUTE ACUTE INFLAMMATIONINFLAMMATION• Neutrophils and monocytes start to Neutrophils and monocytes start to

enlarge to form tissue macrophages.enlarge to form tissue macrophages.• Macrophages maturation can take up Macrophages maturation can take up

to 8 hours and involves swelling of to 8 hours and involves swelling of the cell and formation of large the cell and formation of large quantity of lysosomes.quantity of lysosomes.

• The function of macrophage are The function of macrophage are similar to that of the neutrophil, similar to that of the neutrophil, although macrophages have greater although macrophages have greater and more sustainable killing and more sustainable killing capacities. capacities.

2.1.12.1.1 ACUTE ACUTE INFLAMMATIONINFLAMMATION

• Macrophages and trapped Macrophages and trapped platelets secretes factors that platelets secretes factors that promotes angiogenesis, promotes angiogenesis, promotes chemotaxis and promotes chemotaxis and mitosis for surrounding mitosis for surrounding fibroblast. fibroblast.

• Finally, lymphocyte infiltrate the Finally, lymphocyte infiltrate the wound.wound.

2.1.22.1.2 CHRONIC CHRONIC INFLAMMATIONINFLAMMATION

• Chronic inflammation is a pathological Chronic inflammation is a pathological condition characterized by concurrent condition characterized by concurrent active inflammation, tissue active inflammation, tissue destruction, and attempts at repair. destruction, and attempts at repair.

• Chronic inflammation is not Chronic inflammation is not characterized by the classic signs of characterized by the classic signs of acute inflammation.acute inflammation.

• Instead, chronically inflamed tissue is Instead, chronically inflamed tissue is characterized by: characterized by: – the infiltration of mononuclear immune the infiltration of mononuclear immune

cells (monocytes, macrophages, cells (monocytes, macrophages, lymphocytes, and plasm cells), lymphocytes, and plasm cells),

– tissue destructiontissue destruction– Proliferation of blood vessels and Proliferation of blood vessels and

connective tissue (fibrosis)connective tissue (fibrosis)



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

Comparison between acute Comparison between acute and chronic inflammation: and chronic inflammation:

Acute Chronic

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

Onset Immediate Delayed

Duration Few days Up to many months, or years

OutcomesHealing, abscess formation, chronic inflammation

Tissue destruction, fibrosis

2.22.2WOUND HEALING WOUND HEALING RESPONSERESPONSE

Four stages:Four stages:

1.1. HemostasisHemostasis (seconds to minute) (seconds to minute)

2.2. InflammationInflammation (minutes to day) (minutes to day)

3.3. Proliferative phaseProliferative phase (days to (days to week)week)

4.4. Remodelling phaseRemodelling phase (week to (week to year)year)

INJURY

HEMOSTASIS

INFLAMMATION(Acute Inflammation)


REMODELLING

SCAR TISSUE or FIBROUS CAPSULE DEVELOPMENT

WOUND HEALING RESPONSE

2.22.2 WOUND HEALING WOUND HEALING RESPONSERESPONSE

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