1.Fundamentals Flashcards
Biocompatibility
“The ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response to that specific situation, and optimizing the clinically relevant
performance of that therapy.”
Host response
prevent bacterial colonization, stimulate the healing, resistance to blood clotting, etc.;
Long-term implantable device
“Ability of the device to perform its intended function, with the desired degree of incorporation in the host, without eliciting any undesirable local or systemic effects in that host”.
Scaffolds or matrices for tissue regeneration
“Ability to perform as a substrate that will support the appropriate cellular activity, including the facilitation of molecular and mechanical signaling systems, in order to optimize tissue regeneration, without eliciting any undesirable effects in those cells, or inducing any undesirable local or
systemic responses in the eventual host”.
Tissue Engineering
“The use of cells, biomaterials and suitable molecular or physical factors, alone or
in combination, to repair or replace tissue to improve clinical outcomes”
Scaffold
“A biomaterial structure that serves as a substrate and guide for tissue repair and
regeneration”
1st generation of biomaterial
Materials available in nature such as wood, gold and ivory;
Replacement of a lost tissue function.
2nd Generation of biomaterials
Developed from materials used in several industrial applications;
Example: stainless steel.
Major issues of 2nd Generation of Biomaterials
Weight;
Interaction with biologic tissues
3rd Generation of biomaterials
Functional biomaterials;
Bioactive materials - able to develop strong interactions with the surrounding
environment.
4th Generation of biomaterials
Multifunctional and biomimetic biomaterials;
Recapitulate complex biological constructs formed by nature.
The Biomaterials’ path
1.Reserch on biomaterials
2.Engineering to develop a medical device
3.Preclinical and clinical testing
4.Regulatory approval
5.Commercialization and clinical application
Challenges on the Biomaterial’s path
-define requirements of the biomaterial
-select appropriate biomaterial
-understand how long does it take to develop a biomaterial for clinical use
Steps
1.indentify a need
2.device design
3.material synthesis
4.material testing
5.fabrication
6.sterilization and packaging
7.device testing
8.regulatory
9.clinical use
10.explant analysis
What kind of questions/issues do you realize when thinking about the sterilization of medical implants?
- How would one sterilize a total hip replacement made of a titanium stem, a cobaltchromium
alloy head, and an ultra-high molecular weight polyethylene acetabular shell? - The same method could be employed for all materials?
- How do you ensure that there is no degradation to the material or its structural properties?
- What are the sterilization methods available for medical implants?
- Which method is best suited for a specific biomaterial?
- How sterilization methods affect material properties such as structural and degradation?
Mechanism of Autoclaving
High-pressure steam (121ºC) disables DNA
Benefits of Autoclaving
efficient
easily accessible
Autoclaving Drawbacks
High Temperature
Which materials can be sterilized with autoclaving?
only metals and ceramics
not polymers
Benefits of sterilization with gamma irradiation
efficient
penetrating
Drawbacks of sterilization with gamma irradiation
radiation damage
Benefits of sterilization with electron-beam irradiation
efficient
surface treatment
Which materials can be sterilized with gamma radiation?
metals
ceramics
polymers
Drawbacks of sterilization with electron-beam irradiation
Radiation damage
limited penetration
Which materials can be sterilized with electron beam radiation?
metals
ceramics
polymers
Benefits of sterilization with ethylene oxide gas
no radiation damage
surface treatment
Mechanism of sterilization with ethyleneoxide gas
alkylating agent disables DNA
drawbacks of sterilization with ethyleneoxide gas
requires extra time for outgassing
requires special packaging
Which materials can be sterilized with ethylene oxide gas?
metals
ceramics
polymers
benefits of sterilization with gas plasma
low temperature
no radiation damage
surface treatment
drawbacks of sterilization with gas plasma
limited penetration
requires special packaging
Which materials can be sterilized with gas plasma?
ceramics
metals
polymers
REPAIR
- Natural process augmented by products regulated as drugs, devices, or biologics.
REPLACE
Partly functional replacement of diseased or damaged tissues or organs, often without
replication of natural structure (e.g., prostheses, artificial organs, transplants or grafts).
REGENERATE
Generation of new tissue with functional and structural properties similar to native tissue
or organ.
Bioinert
There are no chemical reactions at the implant–living tissue interface;
* These materials are usually isolated by a layer of fibrous tissue,
although in some cases, they may establish a direct contact with the
adjacent tissue.
Bioactive
Ability to establish chemical bonds with the surrounding tissues;
Example: osseointegration in bone tissue, consisting on the deposition
of collagen and mineral phase directly on the implant surface.
Biomimetic
Biomaterials capable of mimicking natural materials and/or created by inspiration derived from nature;
Strategy explored in several approaches in regenerative medicin
Biomaterials can be processed into different physical forms depending on the application
fibers
meshes
foam
particles
tubular
application in skeletal system
joint replacements
trauma fixation devices
spine disks and fusion hardware
bone defect repair
bone cement
cartilage, tendon, or ligament repair and replacement
dental implant-tooth fixation
applications in cardiovascular systems
vascular grafts,patches
heart valves
pacemakers
implantable defibrillators
stents
catheters
applications in opththalmology
contact lens
intraocular lens
glaucoma drains
which materials can be used in joint replacement applications
Titanium
CoCr
Polyethylene
Alumina
Zirconia
which materials can be used in bone defect repair applications
calcium phosphate
hhuman bone products
which materials can be used in bone cement applications
PMMA
glass polyakkenoate
calcium phosphate cements
which materials can be used in cartilage, tendon, or ligament repair and replacement applications
decellularized porcine tissue
poly(lactide) and metallic fixation devices
collagen
hyaluronic acid lubricants
which materials can be used for pacemakers
titanium
polyurethane
which materials can be used in stent applications
stainless steel
nitinol
CoCr
Mg alloys
PLA
poly(lactic-co-glycolic acid)
which materials can be used in catheters (cardiovacular,urologic and others)
PTFE
poly(ninyl chloride)
silicone
polyurethane
which materials can be used in skin substitutes (chronic wounds, burns)
collagen
cadaver skin
alginate
polyurethane
carboxymethylcellulose
nylon
silicon
which materials can be used in ophthalmologic applications such as contact lenses
PMMA
PHEMA
polyvinyl alcohol
PDMS
which materials can be used for sutures
silk
nylon
poly(glycolic acid)
PLA
polydioxanone
polyester copolymers
polypropylene
PTFE
processed bovine tissue
Medical device ISO 10993
Any instrument , apparatus , implement , machine , appliance , implant , reagent for in vitro use, software, material or other similar (…) intended to be used, alone or in combination, for human being for one or more of the specific medical purpose
Implant ISO 10993
Medical device which is intended to be totally introduced into the human body or to replace an ephitelial surface
advantages of in situ tissue regeneration
-leverage body’s innater regenerative potential
-improved shelf life
-lower cost
-scalable
-consistent quality
Limitations of in situ regeneration
-inneffective for tissue with limited endogenous pregenitor stem cells
-difficult to monitor the regeneration process
Limitations of traditional tissue engineering
-requires compatible cell source
-requires complex culture conditions
-poor homing
-poor engraftment efficacy
-expensive
-donor site morbidity
-immune reaction
Homing
Homing is the phenomenon whereby cells migrate to the organ of their origin. By homing, transplanted hematopoietic cells are able to travel to and engraft (establish residence) in the bone marrow. Various chemokines and receptors are involved in the homing of hematopoietic stem cells.
engraftment
Engraftment is when the blood-forming cells you received on transplant day start to grow and make healthy blood cells.
scaffold types
-monolithic
-microporous
-nanoparticles
-fibrous
-hydrogel network
-3D printed
Biophysical Bulk characterisitics
- viscoelasticity
-stifness
-degradation
Biophysical Surface characterisitics
-guidance
-shape and size
-roughness
-charge
-wetting
Biochemical characterisitics
-chemical structure
-adhesion ligands
-cytokines, antigens, growth factors
-minerals
-anti-infalammatory agents
-reprogramming factors
-spatio-temporal representation
Metods for generation od reactive groups on the surface
plasma treatment
chemical etching
pre-functionalized polymer
Biomaterials physical forms
fibers
meshes
foam particles
tubular
