David F. Williams Excellence in Surface Science

Professor David Williams, D.Sc.,F.R.Eng.,
Professor and Director of International Affairs, Wake Forest Institute of
Regenerative Medicine, North Carolina, USA
Editor-in-Chief, Biomaterials
President-elect, Tissue Engineering & Regenerative Medicine Society International
(TERMIS)
Chairman and Director, Southern Access Technologies, South Africa
Visiting Professor, Christiaan Barnard Department of Cardiothoracic Surgery, Cape Town,
South Africa,
Visiting Professor, Graduate School of Biomedical Engineering, University of New South
Wales, Australia
Guest Professor, Tsinghua University, Beijing and Visiting Professor, Shanghai Jiao Tong
Medical University, China
Emeritus Professor, University of Liverpool, UK
Biocompatibility and War and Peace
Biocompatibility is a war zone
And war is a continuum
Conflict resolution
May lead to quiescence
But peace
Like biocompatibility
Is metastable
Insurgencies, just as thrombus, can occur
At any time
If defences are let down
New technologies
Maybe WMD at the nanoscale
Lead to changes, and
New strategies of defence.
Biocompatibility
Can never be won
It can be tamed
And watched over, for ever
© D.F.Williams 2010
Williams D.F. On the mechanisms of biocompatibility
Biomaterials, 2008, 29, 2941
Williams D.F. On the nature of biomaterials
Biomaterials, 2009, 30, 5897
The Williams Definition of
Biocompatibility
‘The ability of a material to
perform with an appropriate host
response in a specific application’
The Williams Dictionary of Biomaterials
Liverpool University Press, 1999
The Williams Definition of a Biomaterial
2009
A biomaterial is a substance that has been engineered
to take a form which, alone or as part of a complex system,
is used to direct, by control of interactions with components of
living systems, the course of any therapeutic or diagnostic
procedure.
Implantable Medical Devices
Implantable Medical Devices
•Long term biocompatibility and toxicology of metallic
systems are reasonably well known; do we need new alloys?
Implantable Medical Devices
•Long term biocompatibility and toxicology of metallic
systems are reasonably well known; do we need new alloys?
•Long term biocompatibility of biostable polymers is
reasonably well known; do we need new polymers?
Implantable Medical Devices
•Long term biocompatibility and toxicology of metallic
systems are reasonably well known; do we need new alloys?
•Long term biocompatibility of biostable polymers is
reasonably well known; do we need new polymers?
•Long term response of bone to biomaterials is well
understood; do we need new bone-contacting surfaces?
Implantable Medical Devices
•Long term biocompatibility and toxicology of metallic
systems are reasonably well known; do we need new alloys?
•Long term biocompatibility of biostable polymers is
reasonably well known; do we need new polymers?
•Long term response of bone to biomaterials is well
understood; do we need new bone-contacting surfaces?
•Still have some issues with xenogeneic materials
•Still have some uncertainties over interactions with blood –
endothelialization, thromboembolism etc
Biomaterial Performance
Always remember with the biocompatibility of medical devices, the
three most important mediators of clinical performance are, in this
order
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The Quality of the Surgery
The Characteristics of the Patient
The Inherent Biocompatibility of the Material
Implantable Degradable Systems
Implantable Device – Drug Combinations
Implantable Device – Drug Combinations
Drug – eluting stents
BMP releasing devices in the spine
Bisphosphonates in bone
Do we know sufficient about pharmacokinetics and
pharmacodynamics in these systems to be sure of
mechanisms of action, efficacy and safety?
The ability of a material to perform with an appropriate host
response in a specific application
The scientific basis of biocompatibility involves the
identification of the causal relationships
between materials and host tissue such that
materials can be designed to elicit the
most appropriate response
This implies that it is possible to determine
unequivocally the way in which material parameter X
influences host response Y
and that knowing this, we can modify X in order to modulate Y
This is how we should determine the specifications for biomaterials
Material Variables
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Bulk material composition, microstructure, morphology,
Crystallinity and crystallography,
Elastic constants, compliance,
Surface chemical composition, chemical gradient, molecular
mobility,
Surface topography and porosity
Water content, hydrophobic – hydrophilic balance, surface
energy
Corrosion parameters, ion release profile, metal ion toxicity
Polymer degradation profile, degradation product toxicity
Leachables, catalysts, additives, contaminants
Ceramic dissolution profile
Wear debris release profile, particle size
Sterility and endotoxins
Host Response Characteristics
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Protein adsorption and desorption characteristics
Complement activation
Platelet adhesion, activation and aggregation
Activation of intrinsic clotting cascade
Neutrophil activation
Fibroblast behaviour and fibrosis
Microvascular changes
Macrophage activation, foreign body giant cell production
Osteoblast / osteoclast responses
Endothelial proliferation
Antibody production, lymphocyte behaviour
Acute hypersensitivity / anaphylaxis
Delayed hypersensitivity
Genotoxicity, reproductive toxicity
Tumour formation
The Reality for Implantable Devices
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The host response, involving both humoral and cellular
components is extremely complex,
Several of these components involve amplification or cascade
events,
There is often a two-way relationship between the material
variable and the host response e.g. a degradation process is
pro-inflammatory and the products of inflammation enhance the
degradation process,
Mechanical stability influences the host response, and in many
situations the host response determines the stability
The host response is time dependent,
The host response is patient specific, depending on age,
gender, health status / concomitant disease, pharmacological
status, lifestyle, etc.,
Biocompatibility is species specific - testing materials in young
rats in Liverpool or Winston-Salem may be of no relevance to
senior citizens in Atlanta.
The Reality;
Long-term Implantable Devices
It has proved impossible in virtually all situations to
positively modulate the host response by
manipulation of the material variables.
In almost all situations, the practical consequence is
that we select devices that irritate the host the least,
through the choice of the most inert and least toxic
materials and the most appropriate mechanical
design,
The Reality;
Long-term Implantable Devices
• HIPS
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VALVES
ARTERIES
TEETH
ELECTRODES
EYES
PMMA
PE, Co-Cr, Al2O3,
Ti, C, PTFE
PTFE, POLYESTER
Ti
PGM
PMMA, PDMS
The Laws of Biomaterials Selection
When selecting materials for long term implantable
devices, choose the material that optimises the
functional properties of the device, consistent with
maximum chemical and biological inertness
The biocompatibility of a long term implantable
medical device refers to the 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.
Tissue Engineering
Tissue engineering is the creation of new tissue for the
therapeutic reconstruction of the human body, by the
deliberate and controlled stimulation of selected
target cells through a systematic combination of
molecular and mechanical signals
The Changing Nature of Biomaterials and
Methods for their Evaluation
Tissue Engineering Products
We need to assess the intrinsic level of biological risk before a device is
used clinically
 We do not have high quality biomaterials for tissue engineering applications, and
we need new test procedures
 The failure to produce clinical success with tissue engineering products is partly
caused by the lack of standard testing and regulatory approval procedures
 Experience tells us the current pre-clinical test procedures are definitely not
predictive of clinical performance
 ISO 10993 is not a valid basis for testing new biomaterials
We also need effective process validation systems for ensuring continuing
quality and safety
 Do we have the most effective procedures for quality control concerned with
biological safety?
Biocompatibility of Tissue Engineering
Scaffolds and Matrices
The biocompatibility of a scaffold or matrix for a tissue
engineering product refers to the ability to perform as
a substrate that will support the appropriate cellular
activity, including the facilitation of molecular and
mechanical signalling systems, in order to optimise
tissue regeneration, without eliciting any undesirable
local or systemic responses in the eventual host.
Previous FDA approval for the use of a biomaterial in a medical device is not an
appropriate specification for a tissue engineering scaffold or matrix material
•Biocompatibility has to be determined in the context of the
intended function of the product
•We need better systems for the determination of biological
safety
•We may have to re-define ‘surfaces’ in the new world of
nanostructured biomaterials
•We have to take the determination of biocompatibility out of
the courtroom
peggy@morgan-masterson.com