Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell

Biocat, BioRegion of Catalonia
BIOMATERIALS: DE LA SELECCIÓ 
AL DISSENY
Josep A. Planell
Institute for Bioengineering of Catalonia (IBEC)Institute for Bioengineering of Catalonia (IBEC),
CIBER-Bioengineering, Biomaterials and Nanomedicine (CIBER_BBN)
Technical University of Catalonia (UPC) – Barcelona, Spain
linking research, technology and life
www.ibecbarcelona.eu
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Engineering the body - History
484 BC: The Histories by Herodotusy
Hegesistratus, a Persian soldier, was imprisoned by the enemy. In order to escape
from the stocks, he cut off part of his own foot and later wore a wooden replacement.
300 BC: Oldest known prostheses
Roman artificial leg
Biomaterials: used from beginning of civilizationiomaterials: used from beginning of civili ation
Certain materials non related with 
the human body, under certain 
circumstances can be tolerated, or at 
least do not produce acute adverse 
“Kennewick Man” 
(Washington), 9000 years 
old and a spear pointp
reactions that produce irreparable 
damage to their host tissues
old and a spear point 
embedded in his hip
Body’s capacity to deal with 
implanted foreign materials
EVOLUTION OF MATERIALS
XXth Century: Development of the most 
relevant materials for medical applications
Metals and alloys: Stainless steels
cobalt‐chrome alloyscobalt‐chrome alloys
titanium and titanium alloys
other: magnesium, tantalum, niobium
Ceramics: Technological ceramics (alumina and zirconia)
Calcium phosphates
Polymers:  synthetic origin, derived from mineral oily y g ,
Advances in processing and manufacturing technologies
New composites 
EVOLUTION OF MATERIALS
1950’s two phenomena will decide 
the technological evolution of t e tec o og ca e o ut o o
humanity (specially in the field of 
new  materials:
Cold War
Research and development 
fCold War of new weapons
Neither available technology nor available materials 
Space Race
were adequate and advances had to take place in all 
fields: mechanics, welding, new materials resistant 
to heat and materials resistant to low temperatures, p ,
abrasion, new plastics, light alloys, new electronic 
elements, chips, new computing systems, etc.
BIOMATERIALS
Most of XXth Century: Biomaterials were selected among existing 
materials for other industrial applications
Surgeon –Hero:  He designed the first implants looking for materials in 
the chemical, energy, mechanical or aerospatial 
industries
(Sir John Charnley, Sir Harold Ridley, Arthur Vorhees) 
Criteria for selection of biomaterials in the design of implants:Criteria for selection of biomaterials in the design of implants:
 Mechanical and corrosion resistance
 Lightness if possible Lightness if possible
 Availability in different shapes allowing choice for machining and processing
 Easy to sterilize
When Biomaterials Science and Technololgy was just starting, Biomaterials were 
nothing else than industrial materials exhibiting the specific properties of being 
as inert as possible in order to be as harmless as possible upon implantationp p p p
BIOMATERIAL (1991)
A material intended to interface with
bi l i l t t l t t tbiological systems to evaluate, treat,
augment or replace any tissue, organ
or function of the body
BIOMATERIAL HOST BODY
INTERACTIONS
The biomaterial triggers a biological response from the host body
The host body degrades the biomaterialThe host body degrades the biomaterial 
The degradation products elicit a biological response from the host body
PHYSIOLOGICAL ENVIRONMENT
Homeostasis  (local –global)
Equilibrium conditionsEquilibrium conditions 
Chemical (aggressive)( gg )
Physical (non mechanical)
Biological (Inflammation)
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
BIOCOMPATIBILITY (1986)
Ability of a material to perform with
an appropriate host response in a
specific application.
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
STANDARDS AND REGULATIONS
Consensus standards are documents theta have been developed by committees to 
represent a consensus opinion on test methods, materials, devices or procedures.
The application of biomaterials to medical devices is regulated according to the 
intended use of the product incorporating the material and the relative risk of the useintended use of the product incorporating the material and the relative risk of the use 
of the materials. These regulations may be as a result of direct laws or regulations and 
usually take the form of requirements to comply with voluntary or mandatory 
certifications to recognized standards or norms. After a new product has cleared the g p
requirements (which restrict marketing until complete), continuing compliance 
requirements attempt to ensure quality of the finished device.
Typical biomaterial regulatory control follows one or more of the following types:
1 Guidance documents or device specific requirements1. Guidance documents or device specific requirements
2. Adoption by reference to international standards for materials and test requirements
3. Requirements for validation and verification of material performance within the device
4 Manufacturing and purchasing controls to ensure continued quality and performance4. Manufacturing and purchasing controls to ensure continued quality and performance
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
HISTORY OF BIOMATERIALS
• First Generation Biomaterials: materials used industrially in• First Generation Biomaterials: materials used industrially in
other applications that are requested to be inert in the human
body environment. “Biocompatibility” tests.
• Second Generation Biomaterials: designed to be bioactive
d b bland resorbable.
Third Generation Biomaterials b combining these t o• Third Generation Biomaterials: by combining these two
properties, they are being designed to stimulate specific
cellular responses at the molecular level in order to help thep p
body to heal itself.
Lessons from Natural Tissue
H. Fernandes, L. Moroni, C. van Blitterswijk, J. de Boer, J. Mat. Chem. 2009, 19, 5475-5484.
What is Regenerative Medicine?
Regenerative medicine is a
broad concept to define
those innovative medical
therapies that will enable the
bod to repair replacebody to repair, replace,
restore and regenerate
damaged or diseased cellsdamaged or diseased cells,
tissues and organs.
Engineering the body – The future?
REGENERATIVE MEDICINE
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell
41
TISSUE ENGINEERING PROCEDURE
Cell isolationCell isolation Cell ProliferationCell ProliferationCell harvestCell harvest
Cell seeding onCell seeding on
Proliferation or/andProliferation or/and
differentiation in optimaldifferentiation in optimalFilling of the bone defectFilling of the bone defect
scaffoldsscaffolds
differentiation in optimaldifferentiation in optimal
conditionsconditions
Filling of the bone defectFilling of the bone defect
Tissue Engineering (TE) Principle
CELLS
Stem- or progenitor cells
SCAFFOLD S G SSCAFFOLD
Synthetic biomaterial
SIGNALS
Autocrine or added
Bone graft BMPs, other GFs
ARE THESE STATEMENTS, VALID IN MOST INDUSTRIAL FIELDS, 
STILL VALID FOR BIOMATERIALS?
 A (bio)material is not a device
 A device may contain different (bio)materials
 A (bio)material may be used in different devices for different applications
No straightforward answer, however, like ECM, biomaterials will
h t d t /i d (t it/t d ?) bi h i l d
 A (bio)material may be used in different devices for different applications
have to respond to/induce (transmit/transduce?) biochemical and
biophysical(mechanical) stimuli/signals
What should be the material design criteria in order to satisfy in a
quantitative manner the combined stimuli/signals?
Biomaterials:
• Can we generate these signals?Can we generate these signals?
• Surface energy, topography, wetability, surface charges, …
• Soluble factorsSoluble factors.
• Functionalize surfaces with specific signals.
The Biomaterials have now to be designed to generate 
specific signals to cells in order to guide their behaviour. 
They cannot be selected from a list of available 
materials meant for other industrial applications.
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Biomaterials: de la selecció al disseny / IBEC, Josep A. Planell