biomaterials exam 3

biocompatibility

the ability of a material to perform with an appropriate host response in a specific application, how cells interact with material

the FDA only approved

devices- all approvals are for a specific intended use

the characteristics of foreign body response

1. chronic macrophage presence

2. formation of multi-nucleated foreign body giant cells

3. fibrous encapsulation

collagen amount ____ in scare tissue vs pre surgery

increases

fibrous encapsulation

excess fibroblast recruitment, proliferation and collagen synthesis, creating an internal scar to ‘wall-off’ the body from the foreign material,

challenges with fibrous encapsulation

mass transport barrier:

restricts oxygen access

restricts access to biosensors

disrupts communication between neurons and implanted electrodes (microelectronics)

fibrous

a broad range of clinical pathologies accounting for significant human mortality

characteristics of fibrous

chronic activation of myofibroblasts and excessive collagen deposition

mechanism of fibrous

transforming growth factor beta-1 (TGFB-1) responsible for myofibroblast recruitment and activation

causes of fibrous

alcoholism, viral infection, high blood pressure, asbestos, ischemic event)

two populations of macrophages

pro-inflammatory(bad) , pro-healing (good)

types of immune systems

innate and adaptive

innate immune system

non-specific, neutrophils, macrophages

causes inflammation

neutrophils and macrophages

adaptive immune system

bacteria(→ antibodies), viruses(→ T-cells, kill inflected cells)

what causes bacteria

covalescent plasma (blood containing antibodies)

genotype

literal DNA template

phenotype

Observable characteristics of cells

M1 macrophages

classically activated - pro-inflammatory (interferon gamma) (bad)

M2 macrophages

alternatively activated- pro-healing/ pro-resolution (interleukin-4) (good), stimuli platelet derived growth factor

______ is a necessary part of healing

inflammation

what immune system contains the foreign body response

innate

endocrine cytokines

sex hormones

paracrine cytokines

local signaling

endocrine

systematic signals

chemotaxis

directed cell migration up a concentration gradient

angiogenesis

can be used anywhere hypoxia is present ex: vascular sclerosis bypass surgery

osteoblasts

bone cells that are forming new bone

osteoclasts

bone cells (relative of macrophage) that are actively breaking down bone

bone undergoes constant ________, primarily driven by ______ _____

remodeling, mechanical loading

osteoclasts become slightly more active; affects everyone

aging (50+ years)

common is post menopausal females

osteoporosis

exothermic reaction

releases heat, killing bone cells

fixation of orthopedic implants

interface provides mechanical stability

preferred approach is to use surface modification

topography/ roughness

osseointegration

direct structural and functional connection between living bone and the surface of an artificial implant

stress shielding

increase in osteoclasts, decrease in osteoblasts

preferred materials for osseointegration

titanium and its alloys

biomimetic

harness power of biology

tools used thereputically

1. cells

2. biomaterials

3. drug delivery

4. mechanical/ electrical stimuli → topography, stiffness (osseointegration)

solving free body response

degradable materials → polymer processing

polymer processing

1. heat (preferred)

2. solvent

degradable materials

metals, plastics, polymers

drug delivery

traditional pharmaceuticals → proteins → genes → CRISPR

who needs biomaterials

cell therapy (anchorage dependance)

proteins (without protection has short half life)

hydrogels

material that can be fabricated from aqueous solutions + macromolecules

example of a network polymer

volcanized rubber (cross-linking)

monomer example

HEMA- hydroxyethyl methacrylate (unfavorable in situ)

example of a cross linker

EGDMA- ethylene glycol dimethacrylate (functional crosslinker)

why HEMA-hydroxyethyl methacrylate is unfavored

low mw, interacts/ cross cell membrane, low viscosity, high toxicity

naturally derived base materials

collagen/ gelatin

Hyaluronic acid

fibrin → temporary matrix for repair

synthetic base materials

PEG, poly- vinyl alcohol, urethanes, acrylamides NIPAaM

advantages of naturally derived materials

intrinsic support of cell adhesion, inherent biodegradability into non-toxic by products

disadvantages of naturally derived materials

batch to batch variability, possible immunogenicity/ contamination, weak mechanical properties, little control over degredation

synthetic advantages

reproducible manufacturing, affordable, non-immunogenic, controlled properties (degradation/ mechanics)

synthetic disadvantages

lack of bioactivity, lack of bioresponsiveness (can control PLGA degredation rate)

ECM

part of tissue that cells interact with

lost cross links

mechanically weak

cross linking _____ with wound healing

increases

less aminogenic

atelocollagen

bioprosthetic heart value →

tissue → collagen gel

how to create gel

acid-solubilized

gelatin

thermoreversible material (cheap, common, biocompatible)

thermoreversible material

increase temp (liquid soluable), decrease in temp (gel)

advantages of fibrin

fibrinogen contains RGD sequence for integrin-mediated adhesion, proteolytically degradable by plasmin

disadvantages of fibrin

mechanically weak, difficult to control degradation, commercial fibrin glues use very high fibrinogen concentrations + plasmin indication

hyaluronic acid

requires modification to form a gel

hybrid or biosynthetic hydrogels

concept: integrate constituents of nat

Hypoxia →

VEGF induction (trigger)

M1 stimulates

VEGF and activates tip cells

M2 stimulates

PDGF

key roles of VEGF

activates endothelial cells, increases permeability, initiates the angiogenic program

________________ lining nearby vessels and are the primary responders (VEGF)

endothelial cells

angiogenesis

forming new blood vessels

angiogenesis inhibitor

anti-cancer

function of MMPS

proteolytic enzymes that degrade ECM components, especially the basement membranes (collagen, laminin)

pericytes detach from the vessel →

stabilize the vessels and suppress endothelial proliferation, their detachment makes the vessel plastic and permissive to remodeling

pericytes

embedded within the basement membrane, detach early → enable remodeling, reattach later→: stabilize the vessel

endothelial cell migration (sprout initiation)

a subset of endothelial cells become “tip-like”

migrated endothelial cells →

extend filopodia, migrate up the VEGF gradient, navigate through degraded matrix

migration is ________ (VEGF driven) and ________ (requires prior MMP activity)

chemotactic and matrix dependent

endothelial proliferation & sprout extension

behind the leading cells, other endothelial cells proliferate

endothelial proliferation →

VEGF stimulates proliferation, cells elongate and form multicellular sprout

two coupled processes (endothelial proliferation)

migration at the front & proliferation behind → elongation of sprout

tube formation (lumenization)

endothelial cells reorganize into a hollow tube

-cell-cell junctions form

-lumen develops

result of lumenization

a nascent capillary structure capable of carrying blood once connected

vessel maturation and stabilization (PDGF dependent)

endothelial cells secrete (PDGF-B), PDGF recruits pericytes back to new vessel

pericyte functions upon rearrangement

stabilize endothelial cells, suppress excessive proliferation, promote basement membrane re-deposition, ECM is rebuilt → vessel becomes mature and less permeable

VEGF

initiates and drives endothelial activation, migration, and proliferation

MMPs

clear the path by degrading basement membranes and ECM

endothelial cells

execute the program (migration → proliferation → tube formation)