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

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

Engineering the body - History

484 BC: The Histories by HerodotusyHegesistratus, 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 prosthesesRoman 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 steelscobalt‐chrome alloyscobalt‐chrome alloystitanium and titanium alloysother: 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 ohumanity (specially in the field of new  materials:

Cold WarResearch and development fCold War of new weapons

Neither available technology nor available materials 

Space Racewere 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.

BIOMATERIALSMost 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)

BIOCOMPATIBILITY (1986)

Ability of a material to perform with an appropriate host response in a specific application.

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 prequirements (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 requirements2. Adoption by reference to international standards for materials and test requirements3. Requirements for validation and verification of material performance within the device4 Manufacturing and purchasing controls to ensure continued quality and performance4. Manufacturing and purchasing controls to ensure continued quality and performance

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 the p pbody 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 replace body to repair, replace, restore and regenerate damaged or diseased cells damaged or diseased cells, tissues and organs.

Engineering the body – The future?REGENERATIVE MEDICINE

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TISSUE ENGINEERING PROCEDURE

Cell isolation Cell isolation Cell ProliferationCell ProliferationCell harvestCell harvest

Cell seeding on Cell seeding on Proliferation or/and Proliferation or/and differentiation in optimaldifferentiation in optimalFilling of the bone defectFilling of the bone defect scaffoldsscaffoldsdifferentiation in optimal differentiation in optimal

conditions conditions Filling of the bone defectFilling of the bone defect

Tissue Engineering (TE) Principle

CELLSStem- or progenitor cells

SCAFFOLD S G SSCAFFOLDSynthetic biomaterial

SIGNALSAutocrine 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.