Lecture 5 Flashcards
define the term biomaterial
materials that are biocompatible during the time of material-bio system contact.
TIME SCALE is very important
describe the influence of the environment on an implant
1) Blood Supply: Sufficient blood supply is essential for tissue healing and the integration of implants.
2) Infection: Bacterial or viral infections in the vicinity of an implant can be a severe threat. Infections can lead to implant failure by causing inflammation, tissue damage, and bone resorption.
3) Biomechanical Forces: The forces and stresses that an implant is subjected to in its specific location can influence its long-term stability / how the tissue grows.
estimate the terms biocompatible, bioincompatible, bioinert, bioactive, biodegradable, biotolerant
1) biocompatible : no negative influence on body, generates the most appropriate beneficial cellular / tissue response
2) bioincompatible : release of substances in toxic concentrations -> negative reaction
3) bioinert : almost no chemical / biological interaction with body
4) bioactive : positive tissue differentiation (chemical bonding)
5) biodegradable : tissue replaces implant over time
6)biotolerant : weak tissue reactions (fibrous capsule)
describe the influence of the implant to the environment
1) tissue response (inflammation, fibrous capsule,…)
2) osseointegration
3) infection
4) stress shielding
present risks and problems related to hemocompatibility
Platelets are triggered by foreign material -> blood clot (thrombus) forms on artificial surface.
Problems with stents or heart valves for example (restenosis).
describe healing of a bone fracture
starts at periosteum and endosteum.
First blood clot, then callus formation (cartilage), then endochondral ossification (woven bone), then remodelling over time
compare fracture healing to integration of a bone implant
healing process is the same, but foreign material is present when implant
describe biologically relevant structures from the nm to mm length scale
in material : atoms, defects, crystal structure, grains, surface roughness, geometrical design
biosystem : aminoacids, proteins, cell membrane, cell, tissue
explain spatial-temporal behaviour of tissue-material interface in detail
gap between implant and tissue closes over time -> create a stable interface.
First, there is biofluid in the gap (water, proteins, …) and then the tissue grows towards the implant
report which cell types are involved in osseointegration at what point in time
Phase 1 hemostasis : platelets to stop the bleeding and create provisional matrix.
Phase 2 inflammatory :
- endothelial cells move apart
- leukocytes go through the gaps to the injury site and kill bacteria
- macrophages : phagocytosis and stimulate angiogenesis and fibroblasts
Phase 3 proliferative :
- fibroblasts synthesize ECM components
- perivascular cells : angiogenesis, differentiate into osteoblasts (and fibroblasts)
- osteoclasts : resorb bone and create space for healing
- osteoblasts : form new bone (woven bone)
Phase 4 remodeling :
- osetoclasts resorb woven bone and osteoblasts lay down lamellar bone
- osteocytes regulate that process
explain the importance of adsorbing water, proteins and cells on surfaces
adsorbed water + ions : create bonding sites and structures for proteins
proteins : have amino acid sequence that the cell will recognize and attach to (integrin on cell recognizes ONLY surface-bound protein)
cells : can then proliferate or differentiate -> this gives a hint about biocompatibility (if the cells are happy or not)
argue why the cell-surface interaction is important and how it can be changed
It is important for the survival of the cells and to avoid a reaction from the body.
It can be changed by biofunctionalization of surface : add RGD peptide sequence to surface -> surface becomes biomimetic and cell adhesive
describe sequence in which biocompatibility testing usually takes place
1) in-vitro:
- first the material itself (mechanical properties, …)
- then cytocompatibility (assembly)
2) in-vivo :
- material
- assembly
3) clinical trials (humans)
- monocenter
- multicenter
list names of the most important ISO 10993 standards
1 : evaluation and testing
4 : selection of teste for interactions with blood
5 : tests for in-vitro cytotoxicity
explain basic steps during biological risk assessment of medical devices
1) direct or indirect patient contact
2) material composition : equivalence with a commercially available product ? (manufacturing, composition, geometry, …)
3) preliminary assessment (sufficient data ?)
4) final assessment : perform further tests
name the two most important criteria when evaluating biocompatibility
implantation site and implantation time.
ex : surface device, external communicating device, implant device
name tests methods for testing polymers, metals and ceramics
polymers :
- differential scanning calorimetry
- x-ray diffraction
- spectroscopy
- XPS
metals :
- x-ray diffraction
- XPS
- x-ray fluorescence
ceramics :
- x-ray diffraction
- x-ray fluorescence
- microscopy
advantages and limitations to in-vitro and in-vivo testing
1) in vitro
pro:
- controlled environment
- fast and effective
- sensitive quantification of cellular reactions
con:
- too simple
- bad representation of physiological conditions
- cannot replace in-vivo (only one cell type)
2) in-vivo
pro:
- good simulation of human condition
- interaction of different cell types
- immune response
con :
- ethics
- expensive and time-consuming
- demanding protocols
which aspects are investigated to test cytotoxicity (4)
- rate of adhesion
- metabolic activity
- cell proliferation
- cell morphology
how does cell behave depending on cytocompatibility
- rate can be weak or strong
- metabolites can be changes or unchanged
- they can die or proliferate
- they can be globular or outspread
advantages of bioreactors
test how the mechanical forces regulate cell differentiation and tissue formation.
Test force transmission in scaffold.
Important in spinal disks for example.
chemical formula of hydroxyapatite and tricalcium phosphate
HA = Ca10(PO4)6(OH)2
TCP = Ca3(PO4)2
difference between primary cells and continuous cell line
primary : from patient directly -> need a lot to compare outcomes
continous : after in while in culture -> more standardized but act in less natural way