Lecture 5

Question 1

define the term biomaterial

Answer 1

materials that are biocompatible during the time of material-bio system contact.

TIME SCALE is very important

Question 2

describe the influence of the environment on an implant

Answer 2

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.

Question 3

estimate the terms biocompatible, bioincompatible, bioinert, bioactive, biodegradable, biotolerant

Answer 3

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)

Question 4

describe the influence of the implant to the environment

Answer 4

1) tissue response (inflammation, fibrous capsule,…)
2) osseointegration
3) infection
4) stress shielding

Question 5

present risks and problems related to hemocompatibility

Answer 5

Platelets are triggered by foreign material -> blood clot (thrombus) forms on artificial surface.

Problems with stents or heart valves for example (restenosis).

Question 6

describe healing of a bone fracture

Answer 6

starts at periosteum and endosteum.

First blood clot, then callus formation (cartilage), then endochondral ossification (woven bone), then remodelling over time

Question 7

compare fracture healing to integration of a bone implant

Answer 7

healing process is the same, but foreign material is present when implant

Question 8

describe biologically relevant structures from the nm to mm length scale

Answer 8

in material : atoms, defects, crystal structure, grains, surface roughness, geometrical design

biosystem : aminoacids, proteins, cell membrane, cell, tissue

Question 9

explain spatial-temporal behaviour of tissue-material interface in detail

Answer 9

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

Question 10

report which cell types are involved in osseointegration at what point in time

Answer 10

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

Question 11

explain the importance of adsorbing water, proteins and cells on surfaces

Answer 11

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)

Question 12

argue why the cell-surface interaction is important and how it can be changed

Answer 12

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

Question 13

describe sequence in which biocompatibility testing usually takes place

Answer 13

1) in-vitro:
- first the material itself (mechanical properties, …)
- then cytocompatibility (assembly)

2) in-vivo :
- material
- assembly

3) clinical trials (humans)
- monocenter
- multicenter

Question 14

list names of the most important ISO 10993 standards

Answer 14

1 : evaluation and testing
4 : selection of teste for interactions with blood
5 : tests for in-vitro cytotoxicity

Question 15

explain basic steps during biological risk assessment of medical devices

Answer 15

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

Question 16

name the two most important criteria when evaluating biocompatibility

Answer 16

implantation site and implantation time.

ex : surface device, external communicating device, implant device

Question 17

name tests methods for testing polymers, metals and ceramics

Answer 17

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

Question 18

advantages and limitations to in-vitro and in-vivo testing

Answer 18

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

Question 19

which aspects are investigated to test cytotoxicity (4)

Answer 19

• rate of adhesion
• metabolic activity
• cell proliferation
• cell morphology

Question 20

how does cell behave depending on cytocompatibility

Answer 20

• rate can be weak or strong
• metabolites can be changes or unchanged
• they can die or proliferate
• they can be globular or outspread

Question 21

advantages of bioreactors

Answer 21

test how the mechanical forces regulate cell differentiation and tissue formation.

Test force transmission in scaffold.

Important in spinal disks for example.

Question 22

chemical formula of hydroxyapatite and tricalcium phosphate

Answer 22

HA = Ca10(PO4)6(OH)2

TCP = Ca3(PO4)2

Question 23

difference between primary cells and continuous cell line

Answer 23

primary : from patient directly -> need a lot to compare outcomes

continous : after in while in culture -> more standardized but act in less natural way