Biomedical materials engineering
HC1: Biomaterials and biocompatibility
Biomaterials = any substance or combination of substances, other than drugs,
synthetic or natural in origin, which can be used for any period of time, which augments
or replaces partially or totally any tissue, organ or function of the body, in order to
maintain or improve the quality of life of the individual
- E.g.: contact lenses, stents, implants, hearing aid etc.
Biomaterial → refers to any material that is used to replace or augment a part of the
body (e.g., artificial hip joint or a dental implant)
1st generation of biomaterials (1950/1940)
- Created from metals, ceramics, rubber
- Developed for other applications and applied to medicine
2th generation of biomaterials: promote healing and regrowth
- Bioactive, could interact with the body (e.g. form chemical bonds with tissues)
3rth generation: convergence
- Mimicking of the body’s natural 3D structure and simulation/guidance of tissue
generation
3 basic categories of biomaterials:
- Natural, e.g. collagen, fibrin
- Synthetic, e.g. polylactic acid (PLA), polyglycolic acid (PGA)
- Composites, e.g. protein-polysaccharide composite biomaterials,
nanocomposite biomaterials, sponges
Different types of biomaterials
- Biocompatible (e.g. carcinogenicity)
- Anti-infective (e.g. anti-microbial films)
- Anti-inflammatory (e.g. cross reactivity)
- Controlled release (e.g. drug delivery)
Limitations of biomaterials
→ There can be interactions with the patient’s body
- Biomaterials are still different from the actual organ, can limit tissue regeneration
- Most biomaterials have only been able to repair limited sized areas
- Application in the context of more diseases: If it works in one area, does it also
work in another?
→ Ethics
- Ethical concerns about the type and source of materials used
- Is it ethical to use materials taken from humans to make the materials?
→ Regulations
- All safe for patients?
- How to ensure that these new therapies are effective in regenerating damaged
organs and tissues, without harming the patients?
,The meaning of biocompatibility
- Not all biomaterials are biocompatible
- While biomaterials are used in the creation of medical devices and implants,
biocompatibility is a measure of how safe and effective those materials are in the
human body
- Biocompatibility is context dependent, it may work well in one location but not in
another
- What is more important: mechanical performance or biological response? →
biological response, otherwise it can cause harm to the body
- Biocompatibility = the ability of a material to perform with an appropriate host
response in a specific application
ASTM international and international organization for standardization (ISO) →
developed standards for biocompatibility, describe tests involving extracts from
materials that are assessed for bioreacting both in vitro and in vivo
- Material testing
- In vitro testing
- In vivo testing
The importance of biocompatibility testing
- In vitro testing is not always predictive for in vivo biocompatibility → lack of
systemic interactions (e.g. no immune system), oversimplified in vitro situation
(no 3D behavior of cells, no mechanical stresses or pH changes)
- Ethical and practical challenges can arise in biocompatibility testing → use of
animal or human material, testing can be expensive and time consuming
- Regulatory agencies (ISO, FDA) also shape biocompatibility testing
• ISO: Defines which tests are required based on the type of device and
duration of body contact & Provides detailed guidelines for cytotoxicity,
sensitization, irritation, systemic toxicity, hemocompatibility, genotoxicity,
and more
• FDA: Requires manufacturers to demonstrate safety and effectiveness,
often using ISO 10993 as a framework
, - Organ-on-chip models or computational models could replace animal testing in
the future → but still limitations, whole-body responses should be modeled
(organ-on-chip) and high-quality biological data is needed (computational
model)
Road map for an integrated definition of biocompatibility:
- Take into account: material, host (response), manufacturing, application,
validation/testing/assessment etc.
Factors affecting biocompatibility
- Surface topography or chemistry can influence cellular response
• Topography affects cell adhesion, spreading, differentiation
• Chemical composition determines how cells interact with the surface, it
can e.g. be hydrophilic/hydrophobic/changed or have functional groups
like NH2
- The immune system plays a role in biocompatibility → it determines whether a
material will integrate, encapsulate or be rejected (e.g. foreign body reaction &
fibrous capsule formation)
- Patient-specific factors affect material compatibility → age, autoimmune
diseases, diabetes, allergies etc. can affect compatibility
- Processing methods (e.g. sterilization, 3D printing) can alter a materials
biocompatibility → can influence surface properties (e.g. roughness), chemistry
and residual contaminants
, What to take into account when bringing new materials to the market
- Regulations (ISO, FDA)
- Working closely with clinicians to understand needs
- Economics: costs of material/manufacturing and long term impact on healthcare
costs
Limitations and latest advancements in biomaterials research
- Current limitations in designing ‘universal’ biomaterials:
• Biocompatibility is context-dependent, it may work well in one location
but not in another
• Patient variation (age, diseases)
• The complex immune system
- Emerging strategies to improve integration between synthetic and biological
systems:
• Bioactive surfaces: hydrophobic/hydrophilic/chemical functional groups
• Bioengineering: creating tissues from living cells
- Can biodegradable materials fully replace permanent implants in the future? →
no, some applications need long-term support (e.g. hip implants, dental
implants)
HC 2: Regulations and biological evaluation
Part 1
Biocompatibility = the ability of a material to perform with an appropriate host
response in a specific application
- It is not a material property, it is a characteristic of a material-tissue system
- Biocompatibility must be defined in the context of a specific application
Biocompatibility general principles:
- Tissues will treat biomaterials as foreign, but may also show adaption
- Biocompatibility mechanisms do not necessarily progress linearly over time
- Effects may be local or systemic
- Biocompatibility phenomena may vary between patients and on the
administration technique
Biomaterials regulation
- Based on risks → degree of invasiveness, duration of contact
- Risk assessment and risk management, according to ISO
• ISO = a standard to be used by a manufacturer
Regulations in the USA → Food and drug administration (FDA)
- 3 classes based on intended use and risk (premarket notification1 & 2, premarket
approval with clinical data)
HC1: Biomaterials and biocompatibility
Biomaterials = any substance or combination of substances, other than drugs,
synthetic or natural in origin, which can be used for any period of time, which augments
or replaces partially or totally any tissue, organ or function of the body, in order to
maintain or improve the quality of life of the individual
- E.g.: contact lenses, stents, implants, hearing aid etc.
Biomaterial → refers to any material that is used to replace or augment a part of the
body (e.g., artificial hip joint or a dental implant)
1st generation of biomaterials (1950/1940)
- Created from metals, ceramics, rubber
- Developed for other applications and applied to medicine
2th generation of biomaterials: promote healing and regrowth
- Bioactive, could interact with the body (e.g. form chemical bonds with tissues)
3rth generation: convergence
- Mimicking of the body’s natural 3D structure and simulation/guidance of tissue
generation
3 basic categories of biomaterials:
- Natural, e.g. collagen, fibrin
- Synthetic, e.g. polylactic acid (PLA), polyglycolic acid (PGA)
- Composites, e.g. protein-polysaccharide composite biomaterials,
nanocomposite biomaterials, sponges
Different types of biomaterials
- Biocompatible (e.g. carcinogenicity)
- Anti-infective (e.g. anti-microbial films)
- Anti-inflammatory (e.g. cross reactivity)
- Controlled release (e.g. drug delivery)
Limitations of biomaterials
→ There can be interactions with the patient’s body
- Biomaterials are still different from the actual organ, can limit tissue regeneration
- Most biomaterials have only been able to repair limited sized areas
- Application in the context of more diseases: If it works in one area, does it also
work in another?
→ Ethics
- Ethical concerns about the type and source of materials used
- Is it ethical to use materials taken from humans to make the materials?
→ Regulations
- All safe for patients?
- How to ensure that these new therapies are effective in regenerating damaged
organs and tissues, without harming the patients?
,The meaning of biocompatibility
- Not all biomaterials are biocompatible
- While biomaterials are used in the creation of medical devices and implants,
biocompatibility is a measure of how safe and effective those materials are in the
human body
- Biocompatibility is context dependent, it may work well in one location but not in
another
- What is more important: mechanical performance or biological response? →
biological response, otherwise it can cause harm to the body
- Biocompatibility = the ability of a material to perform with an appropriate host
response in a specific application
ASTM international and international organization for standardization (ISO) →
developed standards for biocompatibility, describe tests involving extracts from
materials that are assessed for bioreacting both in vitro and in vivo
- Material testing
- In vitro testing
- In vivo testing
The importance of biocompatibility testing
- In vitro testing is not always predictive for in vivo biocompatibility → lack of
systemic interactions (e.g. no immune system), oversimplified in vitro situation
(no 3D behavior of cells, no mechanical stresses or pH changes)
- Ethical and practical challenges can arise in biocompatibility testing → use of
animal or human material, testing can be expensive and time consuming
- Regulatory agencies (ISO, FDA) also shape biocompatibility testing
• ISO: Defines which tests are required based on the type of device and
duration of body contact & Provides detailed guidelines for cytotoxicity,
sensitization, irritation, systemic toxicity, hemocompatibility, genotoxicity,
and more
• FDA: Requires manufacturers to demonstrate safety and effectiveness,
often using ISO 10993 as a framework
, - Organ-on-chip models or computational models could replace animal testing in
the future → but still limitations, whole-body responses should be modeled
(organ-on-chip) and high-quality biological data is needed (computational
model)
Road map for an integrated definition of biocompatibility:
- Take into account: material, host (response), manufacturing, application,
validation/testing/assessment etc.
Factors affecting biocompatibility
- Surface topography or chemistry can influence cellular response
• Topography affects cell adhesion, spreading, differentiation
• Chemical composition determines how cells interact with the surface, it
can e.g. be hydrophilic/hydrophobic/changed or have functional groups
like NH2
- The immune system plays a role in biocompatibility → it determines whether a
material will integrate, encapsulate or be rejected (e.g. foreign body reaction &
fibrous capsule formation)
- Patient-specific factors affect material compatibility → age, autoimmune
diseases, diabetes, allergies etc. can affect compatibility
- Processing methods (e.g. sterilization, 3D printing) can alter a materials
biocompatibility → can influence surface properties (e.g. roughness), chemistry
and residual contaminants
, What to take into account when bringing new materials to the market
- Regulations (ISO, FDA)
- Working closely with clinicians to understand needs
- Economics: costs of material/manufacturing and long term impact on healthcare
costs
Limitations and latest advancements in biomaterials research
- Current limitations in designing ‘universal’ biomaterials:
• Biocompatibility is context-dependent, it may work well in one location
but not in another
• Patient variation (age, diseases)
• The complex immune system
- Emerging strategies to improve integration between synthetic and biological
systems:
• Bioactive surfaces: hydrophobic/hydrophilic/chemical functional groups
• Bioengineering: creating tissues from living cells
- Can biodegradable materials fully replace permanent implants in the future? →
no, some applications need long-term support (e.g. hip implants, dental
implants)
HC 2: Regulations and biological evaluation
Part 1
Biocompatibility = the ability of a material to perform with an appropriate host
response in a specific application
- It is not a material property, it is a characteristic of a material-tissue system
- Biocompatibility must be defined in the context of a specific application
Biocompatibility general principles:
- Tissues will treat biomaterials as foreign, but may also show adaption
- Biocompatibility mechanisms do not necessarily progress linearly over time
- Effects may be local or systemic
- Biocompatibility phenomena may vary between patients and on the
administration technique
Biomaterials regulation
- Based on risks → degree of invasiveness, duration of contact
- Risk assessment and risk management, according to ISO
• ISO = a standard to be used by a manufacturer
Regulations in the USA → Food and drug administration (FDA)
- 3 classes based on intended use and risk (premarket notification1 & 2, premarket
approval with clinical data)
