Host response to biomaterials 8MM50
Lecture 1 – Course introduction
Most implants have huge effect on the human body. For example:
• Tattoo ink was found in all parts of the body, not just skin but also lymph nodes
• Breast implants often cause many issues, some can even give rise to cancer
• After birth the pelvic floor often starts to weaken, a pelvic mesh can reinforce this pelvic floor but this
gave a lot of issues
Thus, the safety of biomaterials need to be investigated thoroughly.
What can go wrong with implants?
• Scarring & tissue: contraction due to the wound
that has to be made. This can result in
dysfunction of your tissues.
• Graft rejection
• Thrombosis
• Mechanical failure, implant can break
• Stress shielding adverse remodeling (e.g.
bone resorption) this often happens with hip
implants as your bone no longer receives any
load and it resolves.
• Toxic degradation products
• Autoimmune disorders
• (infection)
Immunomodulatory biomaterials
• There is no such thing as an ‘inert’ biomaterial, you cannot make anything to which your body will not
respond to.
• Host response is not bad
• Interact with/instruct the immune system as opposed to trying to prevent the host response.
Examples
Biomaterials that induce tissue regeneration.
• A collagen decellularized scaffold is inserted that can modulate the immune response so that functional
tissue regrows (and not scar tissue)
• Plastic scaffold that degrades very slowly, when it is implanted it triggers immune response which then
triggers regeneration.
Immunomodulatory biomaterials to fight cancer by silencing/activating immune cells
• Can be done with nanoparticles which can active T cells to attack the cancer cells
• Development of artificial lymph node = synthetic immune niche, attracts cells. Cells can go in this lymph
node where they can be exposed to certain stimuli which results in attacking of the cancer cells
1
,Different length scales
• Nanoscale
o Nanoparticles: to specifically target immune cells, either to their surface receptors or inside immune
cell and trigger them to do something
• Micro scale
o Capsules that are used to deliver certain drugs or cells in to your body and trigger response
o Artificial antigen presenting cells (AAPC): this mimics what antigen presenting cell does
• Macro scale
o Scaffolds/ surface of an implant, like coating or a whole heart valve/ cartilage implant/hydrogel
Biomaterial applications
Replacement (permanent)
• Joint prosthesis
• Dental implants
• Artificial heart valves
• LVAD
• Pacemaker
• Vascular stent
Biocompatibility
Polypropylene mesh:
• Non-toxic
• Non-antigenic
• Material approved by Food and Drug Administration (FDA) (so safe)
Biocompatibel? It can be in some cases
Biocompatibility is not toxicology (is biomaterial toxic or not)
• Wrong definition biocompatibility: “The quality of not having toxic or injurious effects on biological
systems”
• Correct definition biocompatibility: “The ability of a material to perform with an appropriate host
response in a specific application”
Factors which influence host response
Biomaterial-related factors
• Composition (material)
• Degradability: is it degradable, how does it degrade,
how long?
• Mechanical properties
• Sterility
• Antigenicity
• Active ingredients (drugs)
2
,Lecture 2 – The Foreign Body Response (Part 1)
Innate and adaptive immune system
• First line of defense: mechanical barriers (e.g. skin, mucus membranes)
• Second line of defense: innate immune system
• Third line of defense: adaptive immune system
Example: Neutrophils in the blood vessel attack incoming parasites, which can happen within an hour.
Innate:
• Non specific
• Responds quick
Adaptive:
• Specific – antigens
• Responds slowly the first time
• Memory
Innate immune response plays an important role when a synthetic, acellular biomaterial is being placed. These
are typically not antigenic. Your adaptive immune cells play role in FBR.
Adaptive immune response: responses to antigens (APC: DCs, macrophages)
Innate immune response
The cells are phagocytes, main job to eat stuff. This happens nonspecifically.
1. Granulocytes or polymorphonucleated cells (PMNs): Mainly neutrophils (eat or detonate)
short-lived kamikaze cells: move to the location, eat there, then release granules to attract
more cells.
2. Monocytes circulate in blood, once activated they differentiate to macrophages (eat or
encapsulate) Robust siege cells: they try to eat whatever is there and then degrade it, if
they cannot they try to shield the threat by encapsulating it.
3
, These phagocytes can be activated by two types of signals:
1. They have pattern recognition receptors (PRRs) recognize
danger signals
a. Match with specific pattern
2. Integrins bind to substrate (ECM/biomaterial)
PRRs recognize molecular patterns
1. Pathogen-Associated Molecular Patterns (PAMPs)
a. Ex.: Little bits of bacteria or a virus
2. Damage-Associated Molecular Patterns (DAMPs)
a. Also known as alarmins
b. Danger signals from own body, ex. if there is damage in
your body specific molecular patterns that are normally
in your cell come out and can be recognized. Or, if there
are small bits of ECM such as collagen peptides, this is
sign of damages.
c. Necrotic cells cytoplasmic & nuclear
components (e.g. Heat shock protein (HSP) or
HMG-1, these are normally inside your cell)
d. Damaged ECM ECM fragments.
Can be seen as ‘eat me’ signals.
Most important receptors
• Toll-like receptors
• Nod-like receptors
• C-type lectin receptor
Once something binds to these receptors, it can trigger a
function of the cell.
These receptors are targets for immunomodulatory
strategies.
Antigen presentation – macrophages & DCs
• Macrophages & DCs eat stuff and show what
it ate to a T-cells (adaptive immune system).
• Phagocyte binds with PAMP of bacteria (ex.)
through PRR this is internalized (eaten up)
causes inflammation then it can
present the bacteria to T-cell.
Ex. Tattoo-ink on skin is seen on the lymph nodes: macrophages and DCs
recognize particles of tattoo-ink as foreign and bring it to lymph node to
activate T cell and thus the adaptive immune system.
4
Lecture 1 – Course introduction
Most implants have huge effect on the human body. For example:
• Tattoo ink was found in all parts of the body, not just skin but also lymph nodes
• Breast implants often cause many issues, some can even give rise to cancer
• After birth the pelvic floor often starts to weaken, a pelvic mesh can reinforce this pelvic floor but this
gave a lot of issues
Thus, the safety of biomaterials need to be investigated thoroughly.
What can go wrong with implants?
• Scarring & tissue: contraction due to the wound
that has to be made. This can result in
dysfunction of your tissues.
• Graft rejection
• Thrombosis
• Mechanical failure, implant can break
• Stress shielding adverse remodeling (e.g.
bone resorption) this often happens with hip
implants as your bone no longer receives any
load and it resolves.
• Toxic degradation products
• Autoimmune disorders
• (infection)
Immunomodulatory biomaterials
• There is no such thing as an ‘inert’ biomaterial, you cannot make anything to which your body will not
respond to.
• Host response is not bad
• Interact with/instruct the immune system as opposed to trying to prevent the host response.
Examples
Biomaterials that induce tissue regeneration.
• A collagen decellularized scaffold is inserted that can modulate the immune response so that functional
tissue regrows (and not scar tissue)
• Plastic scaffold that degrades very slowly, when it is implanted it triggers immune response which then
triggers regeneration.
Immunomodulatory biomaterials to fight cancer by silencing/activating immune cells
• Can be done with nanoparticles which can active T cells to attack the cancer cells
• Development of artificial lymph node = synthetic immune niche, attracts cells. Cells can go in this lymph
node where they can be exposed to certain stimuli which results in attacking of the cancer cells
1
,Different length scales
• Nanoscale
o Nanoparticles: to specifically target immune cells, either to their surface receptors or inside immune
cell and trigger them to do something
• Micro scale
o Capsules that are used to deliver certain drugs or cells in to your body and trigger response
o Artificial antigen presenting cells (AAPC): this mimics what antigen presenting cell does
• Macro scale
o Scaffolds/ surface of an implant, like coating or a whole heart valve/ cartilage implant/hydrogel
Biomaterial applications
Replacement (permanent)
• Joint prosthesis
• Dental implants
• Artificial heart valves
• LVAD
• Pacemaker
• Vascular stent
Biocompatibility
Polypropylene mesh:
• Non-toxic
• Non-antigenic
• Material approved by Food and Drug Administration (FDA) (so safe)
Biocompatibel? It can be in some cases
Biocompatibility is not toxicology (is biomaterial toxic or not)
• Wrong definition biocompatibility: “The quality of not having toxic or injurious effects on biological
systems”
• Correct definition biocompatibility: “The ability of a material to perform with an appropriate host
response in a specific application”
Factors which influence host response
Biomaterial-related factors
• Composition (material)
• Degradability: is it degradable, how does it degrade,
how long?
• Mechanical properties
• Sterility
• Antigenicity
• Active ingredients (drugs)
2
,Lecture 2 – The Foreign Body Response (Part 1)
Innate and adaptive immune system
• First line of defense: mechanical barriers (e.g. skin, mucus membranes)
• Second line of defense: innate immune system
• Third line of defense: adaptive immune system
Example: Neutrophils in the blood vessel attack incoming parasites, which can happen within an hour.
Innate:
• Non specific
• Responds quick
Adaptive:
• Specific – antigens
• Responds slowly the first time
• Memory
Innate immune response plays an important role when a synthetic, acellular biomaterial is being placed. These
are typically not antigenic. Your adaptive immune cells play role in FBR.
Adaptive immune response: responses to antigens (APC: DCs, macrophages)
Innate immune response
The cells are phagocytes, main job to eat stuff. This happens nonspecifically.
1. Granulocytes or polymorphonucleated cells (PMNs): Mainly neutrophils (eat or detonate)
short-lived kamikaze cells: move to the location, eat there, then release granules to attract
more cells.
2. Monocytes circulate in blood, once activated they differentiate to macrophages (eat or
encapsulate) Robust siege cells: they try to eat whatever is there and then degrade it, if
they cannot they try to shield the threat by encapsulating it.
3
, These phagocytes can be activated by two types of signals:
1. They have pattern recognition receptors (PRRs) recognize
danger signals
a. Match with specific pattern
2. Integrins bind to substrate (ECM/biomaterial)
PRRs recognize molecular patterns
1. Pathogen-Associated Molecular Patterns (PAMPs)
a. Ex.: Little bits of bacteria or a virus
2. Damage-Associated Molecular Patterns (DAMPs)
a. Also known as alarmins
b. Danger signals from own body, ex. if there is damage in
your body specific molecular patterns that are normally
in your cell come out and can be recognized. Or, if there
are small bits of ECM such as collagen peptides, this is
sign of damages.
c. Necrotic cells cytoplasmic & nuclear
components (e.g. Heat shock protein (HSP) or
HMG-1, these are normally inside your cell)
d. Damaged ECM ECM fragments.
Can be seen as ‘eat me’ signals.
Most important receptors
• Toll-like receptors
• Nod-like receptors
• C-type lectin receptor
Once something binds to these receptors, it can trigger a
function of the cell.
These receptors are targets for immunomodulatory
strategies.
Antigen presentation – macrophages & DCs
• Macrophages & DCs eat stuff and show what
it ate to a T-cells (adaptive immune system).
• Phagocyte binds with PAMP of bacteria (ex.)
through PRR this is internalized (eaten up)
causes inflammation then it can
present the bacteria to T-cell.
Ex. Tattoo-ink on skin is seen on the lymph nodes: macrophages and DCs
recognize particles of tattoo-ink as foreign and bring it to lymph node to
activate T cell and thus the adaptive immune system.
4
