Biocompatibility: Evaluation and Risk Assessment Flashcards
toxicity
describes the ability of a material to damage a biological system by chemical means
may be local or systemic
immunotoxicity
describes the adverse effects on the structure and function of the immune system
autograft
donor and recipient are the same person
allograft
donor and recipient are from the same species
xenograft
donor and recipient are from the different species
risk is a combination of
hazard and exposure
in vitro biocompatibility assessment
isolated cells derived from animal or human tissues are grown in culture plates and used for testing
three primary cell culture assays are used for evaluating compatibility
direct contact
agar diffusion
elution testing
cell lines
immortalized cells, some are from normal cells, others from tumors
effectively they are clones of the original donor
good: established and commercially available, genetically uniform, lower cost
bad: some genetic manipulation required to achieve immortality, may not function as target cells type, may not be available for target cell types and species
not for human use due to immunogenicity, research tool only
primary cells
isolated directly from animal or human tissues
good: closest to the real cell, can be patient specific
bad: difficult to grow, limited proliferation capacity, heterogeneous, immunogenic, difficult to reproduce
how can i test biocompatibility on a specific patient
stem cells
personalized induced stem cell will carry your genetic characteristic and unique response toward biomaterials
direct contact assay
biomaterial is placed directly over or under cultured cells
agarose diffusion assay
biomaterial is separated from cultured cells by a thin layer of agarose
elution assay
biomaterial is incubated in medium for an extended period of time to extract leachable compounds
the conditioned media will then be used to culture cells in a separately prepared dish
direct contact advantages
no extract preparation
zone of diffusion
target cell contact with material
standardize amount of test material or test indeterminate shapes
disadvantages of direct contact
cellular trauma if material moves
cellular trauma with high density materials
agar diffusion advantages
no extract preparation
zone of diffusion
can test one side of material, independent of material density
disadvantages of agar diffusion
requires a flat surface
risk of absorbing water from agar
solubility of toxicant in agar
advantages of elution
dose response effects
extended exposure times
choice of extract conditions
disadvantages of elution
time required for preparation
cytotoxicity vs viability
based on physical and/or physiological differences between live and dead cells
metabolic assays
based on the conversion of one dye to another in the presence of metabolically active environment
cell number is determined using standard curve
underlying assumption that cells have constant metabolic rate
viability assay based on constants that reflect cell number
one can estimate the number of cells by measuring the number of ATP molecules
generally the number of ATP molecule per cell is constant
metabolically active cell converts ADP back into ATP faster compared to dormant cells
combining cell number assay and metabolic assay
these two end points don’t measure the same thing
cell number –> measure of cell death (important of acute biocompatibility
metabolic assay –> cell health (slow does not equal death)
in vitro model is an excellent tool to determine
lack of biocompatibility
in vivo implant models
non-functional test
functional test
non-functional in vivo implant models
focus on direct interactions between the substance and chemical and biological nature of implant environment
functional test in vivo implant models
functional model that it test the device as intended
limitations of in vivo implant models
interspecies variation, local tissue conditions that are abnormal in some species may be chronic in others, infection, variable metabolism, variable lifetimes
