BIO-MAT test #2

Slip

process by which plastic deformation is produced by dislocation motion

Slip plane

The crystallographic plane along which the dislocation traverses

Solid solution strengthening

Technique to strengthen and harden metals by adding impurity atoms

Alloys

stronger than pure metals because impurity atoms impose lattice strain onto host atoms

Solute atoms

tend to diffuse and segregate around dislocations to minimize strain energy

Strain hardening

ductile metals become stronger and harder as they are plastically deformed

recrystallization

The formation of a new set of strain-free grains that have low dislocation densities and are characteristic of precold-worked conditions

Annealing

heat treatment where the material is exposed to elevated temperature and then slowly cooled

stress relaxation

at a constant strain and temperature, stress decreases with time due to molecular relaxation processes that take place within the polymer

Viscoelastic creep

time dependent deformation when stress is held constant

Drawing

permanently deforming the polymer material in tension to improve modulus and strength

Protein structure

Integrins

adhesion receptors involved in cell adhesion to biomaterials and extracellular matrices (ECMs)

Vroman effect

A dynamic process where proteins that are adsorbed first can be replaced over time

Nonfouling surfaces (NFSs)

surfaces that resist the adsorption of proteins and/or adhesion of cells

Delamination

separation of a multi-layered material into individual layers

in vitro

perfomed outside of living organism

contact inhibition

cell growth and proliferation stop when cells come into contact with one another

Mechanotaxis

Cells migrate based on mechanicalgradient

Cell polarization

cytoplasmic cellular components become asymmetrically distributed along an axis

Mechanotransduction

The conversion of external mechanical signals into intracellular chemical or physical events

Thrombosis

the formation of a blood clot or thrombus

hemostasis

The mechanism that leads to cessation of bleeding

Virchow’s triad

Factors important for the Formation of thrombosis includes vessel wall injury, hypercoagulability, and flow disturbance

Stenosis

An obstruction to flow commonly caused by narrowing of the vessel

in-stent restenosis (ISR)

recurrence of stenosis after a stent is implanted

(Mechanical failure)

(disturbed blood flow)

(injury to endothelial cells)

(chronic inflammation)

Hemostasis

Cells and tissues attempt to maintain their milieu and function within a relatively narrow range of physiologic parameters

Necrosis

Death of living tissue

Hypertrophy

Increase in size of individual cells

Hyperplasia

Increase in cell number

Atrophy

Decrease in size, without appreciable change in cell number

Metaplasia

Transformation from one mature cell type to another

Hypoxia

Decrease in O2 supply relative to the needs of a particular cell or tissue

Apoptosis

Programmed cell death

Acute inflammation

Immediate response to injury (1-3 days)

Chronic inflammation

Involves macrophage recruitment and sometimes lymphocytes

Macrophage

A phagocytic cell associated with chronic inflammation

(secrete wide variety of biologically active molecules importnat for mediating tissue destructon, formation of new blood vessels, and fibrosis)

Size Exclusion Chromatography (SEC)

Used to determine molar mass and dispersity of polymers

Mechanical Testing

used to view how materials act under stress and strain

Rheology

measure how materials flow and deform under applied forces

Scanning Electron Microscopy (SEM)

An electron microscope that images a sample's surface by scanning it with a high-energy focused beam of electrons

Energy Dispersive X-ray Spectroscopy (EDS)

It identifies elements by measuring characteristic X-rays emitted from a sample when bombarded by a high-energy electron beam. (usually used with SEM)

Contact angle Goniometry

Measures the contact angle between the solid surface and the liquid

IR spectroscopy

IR absorbance spectra of a sample can be compared to the reference spectra to determine molecular bond vibrations

DIfferential Scanning Calorimetry (DSC)

The thermal analysis technique measures how much heat a material absorbs or releases as it is heated or cooled at a constant rate, input by the operator.

Cytotoxicity Assay

Screens compound libraries for toxicity by detecting markers for severe cell damage

Biocompatibility

The ability of a material to perform with an appropriate host response in a specific application

Events Following Implantation

Foreign body reaction (FBR)

Protein adsorption, Acute inflammation, Chronic inflammation, Fibrous capsule

Foreign body giant cells

fusion of macrophages in response to foreign materials

Fibrosis

The formation of fibrous connective tissue that is hardened and/or includes scar tissue

• dense, aligned collagen produced by fibroblasts

• Harmful: mass transfer barrier

• The lifetime of device

Capsular Contracture

fibrous capsule contracts over time, leading to implant deformation, stiffness, and possibly failure

Histology

he microscopic study of the structure, organization, and function of plant and animal tissues

Biodegradation

chemical breakdown of materials by the action of living organisms that leads to changes in physical properties

Hydrolysis

The scission of susceptible functional groups by aqueous attack

hydrolase

Hydrolytic enzymes are cell-derived proteins which act as highly specific catalysts for chain scission of water-labile functional groups

Calcification

Formation of nodular deposits of calcium phosphate or other calcium-containing compounds may occur on biomaterials used in the circulatory system.

Depletion studies

analysis designed to measure the reduction of a specific resource, agent, or capacity

Monolayer Model

• Space occupied per protein molecule in a close-packed

layer varies depending on the adsorption conditions

Low Conc.: given time to spread molecularly and proteins tend to be tightly bound

High Conc.: sites fill rapidly with proteins, so spread is inhibited, resulting in looser and higher concentrations of proteins.

Competetive adsorption

The relative enrichment of a given protein when adsorbed from a complex mixture is unique to each protein studied

Surface chemistry & protein adsorption

• Adsorbed proteins are required for platelet adhesion

• One approach to improve biocompatibility is to prevent/reduce protein adsorption

• PEO and PEG are good at preventing protein adsorption. Though PCB and PSB are better. (these are nonfouling surfaces)

surface modifications

Process of cell attachment

• adsorbed Protein layer

• Cells make contact and anchor to the adsorbed layer on focal adhesions

• Integrins attach to specific anchoring proteins (fibronectin, collagen, vitronectin, laminin)

• Adherent cells are flatter, while non-adherent or dead cells are spherical.

effect of mechanical forces

• regions of the arterial systems become prone to atherosclerosis due to low shear stress

• Vascular smooth muscle cells, the middle layer in arteries, migrate in response to mechanical forces.

• The outer layer of arteries consists of fibroblasts and the extracellular matrix (ECM)

VASCULAR:

• regions of low shear stress, flow reversal, or gradients in shear stress have an increased probability of vascular disease

Objectives

Description of overall project goals

Criteria

Measureable requirements a design must acheive to be successful

Constraints

Limitations or boundaries that the design must operate within

Best tissue function WHEN?

• pH, Temperature, nutrition, pressure, etc.

• in event of variations in the internal & external environment, organs, tissues, and even individual cells strive to acheive homeostasis.

Injury (reversible & non-reversible)

• Persistent or excessive injury causes cells to pass through the threshold into irreversible injury

• At 55 degrees C, cells start to die (necrosis)

• Chronic stress leads cells and tissues to undergo adaptation to achieve now stead state to preserve tissue function.

• Toxic Chemicals

• , mechanical force, Temp, Electric shock, ionizing radiation

• , infection and inflammation (bacteria have toxic cells wall components [endotoxins])

Fibrin

tough, fibrous protein essential for blood clotting (hemostasis) and wound healing

• when the enzyme thrombin converts fibrinogen into insoluble fibrin monomers

Coagulation cascade

• Protein adsorption (like fibrinogen) + platelet interaction → activates clotting

• Poor hemocompatibility = excess thrombin → thrombosis

• Thrombosis + fibrinogen —→ fibrin

• excess fibrin —→ clotting

Scarring (fibrosis)

• progressive degradation of damaged tissue, formation of new blood vessels, and remodeling of the ECM

• reconstruction of normal structure requires intact extracellular matrix.

Host responses

Beneficial: vascularized tissue, a thin fibrous capsule, integration

Harmful: thick fibrous and avascular capsule, scar formation, chronic inflammation

Sequence of events following implantation (FBR)!!!!!!

1. Non-specific protein adsorption

2. Acute inflammation (minutes - days)

• Recruitment of primarily neutrophils (engulfing pathogens)

• Cytokine release to attract more immune cells (neutrophils, Macrophages)

3. Chronic inflammation (weeks - years)

• Macrophage (from monocytes) recruitment and fusion into foreign body giant cells (FBGCs)

• Macrophages release growth factors to promote new blood vessel formation

4. Fibrous capsule formation

• fibroblasts deposit dense collagen fibers and extracellular matrix around the foreign object, creating a scar.

sequence of host response following implantation

Granulation tissue is new connective tissue (Healing phase of inflammation)

• Initiated by macrophages (release of signaling molecules from them)

• Proliferation of fibroblasts, synthesis of collagen, and new blood vessel formation.

• Can occur 3-5 days after injury

Final stage of biomaterial inflammation:

• FBGCs and macrophages

• FBGCs form from macrophages trying to engulf a surface that is too large, leading to

• Associated with stress cracking at the biomaterial surface

In Vivo studies

• assesses tissue compatibility

• Replacement, reduction, & refinement

• Animal Welfare Act (select right amount, type of animal)

Body environment

• Aqueous salt solution

• 37 C

• can lead to plasticizing of polymers

• Macrophages release oxidizing agents and enzymes intended to digest material

Degradation

• stabilizing against degradation (cross linking)

• Oxidative degradation

• hydrolysis (H20 slicing)

• gamma radiation