introduction to biomaterials science - aalto to biomaterials science emilia peltola, dsc 7.9.2015. 4...

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Emilia Peltola, DSc

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Biomaterials &biocompatibility

Protein adsorption

Criteria for the selectionof biomaterials

Introduction to BiomaterialsScience

Emilia Peltola, DSc

7.9.2015

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Contents

Practicalities

Biomaterials & biocompatibility

Protein adsorption

Criteria for the selection of biomaterials

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Protein adsorption


ELEC-E8724 Biomaterials Science

Responsible teacher Emilia Peltola (@aalto.fi)Several visiting lecturers

I Lectures mon/thu 12:15 – 14:00, I-periodI Seminars mon/thu 12:15 – 14:00, 12.-23. Nov

Course requirementsI 4 home assignments (a grade in each is required)I Seminars (seminar work & peer review &

participation into minimum two seminars)I Home exam

Grading: Home assignments (1/3), seminar (1/3),home exam (1/3)

https://mycourses.aalto.fi/course/view.php?id=5274&section=2




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Course book

Ratner et al., BiomaterialsScience – An Introductionto Materials in Medicine,3rd edition, 2013(available as E-book)

Applicable parts (listed atthe end of slides) only!

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Course aims

I differentiate the biomaterials in medicine and theircentral properties

I understand the requirements set by thebiomedical applications

I know biomaterial-tissue interactionsI comprehend how to modify biocompatibility

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Biomaterials & Biocompatibility

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Brainstorming I

What kind of implants can you name?

http://presemo.aalto.fi/biomaterials/


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Definition of biomaterials

A biomaterial is a material intended to interface withbiological systems to evaluate, treat, augment, orreplace any tissue, organ or function of the body.

ESB Consensus Conference II

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Applications

Biomaterials are integrated into biomedical devices toimprove quality of life

i.e. biomaterials keep the legs moving, heart beating,ears hearing, blood flowing, eyes seeing.

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Examples of biomaterials

Metals Polymers Ceramics Biologicalmaterials

e.g. titanium, e.g. UHMWPE, e.g. alumina, e.g. chitin,stainless steel PMMA bioglass nacre

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Some history

Sutures(linen,catgut)

Goldin den-tistry

Nacretooth

implant

Pumpsandcell

culture

Intraocularlenses

Hipprost-heses

Vascularprost-heses

Artificialheart,kidney

30,000 B.C. 600 B.C. 1940s 1950s

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Biocompatibility

First generation of implants (1940–80): chemicallyinert materials

I non-toxic, non-immunogenic, non-thrombogenic,non-carcinogenic, non-irritating etc.

Definition was insufficient, because...

1. the host response depends on the application2. biodegradable applications were needed3. bioactive applications were needed

Williams 1987: ”the ability of a material to perform withan appropriate host response in a specific application”

I new kind of applications (tissue engineering, etc.)require more specific definition→

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Definition of biocompatibility

”Biocompatibility refers to the ability of a biomaterial toperform its desired function with respect to a medicaltherapy, without eliciting any undesirable local orsystemic effects in the recipient or beneficiary of thattherapy, but generating the most appropriatebeneficial cellular or tissue response in thatspecific situation, and optimising the clinicallyrelevant performance of that therapy.”

[Williams, 2008]

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Criteria for the selectionof biomaterialsBiocompatibility and different applications

Exercise 1

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Some applications

Application Number/Year – WorldJoint replacements 2,500,000Blood vessel prosthesis 200,000Heart valve 400,000Pacemaker 600,000Implantable defibrillator 300,000Stent 1,500,000Catheter 1,000,000,000Contact lens 150,000,000Intraocular lens 7,000,000

[Ratner et al., 2013]

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Some applications - fail

Application StateJoint replacements still a 10-15 yr lifetimeBlood vessel prosthesis no healingHeart valve calcification or thrombosisPacemaker electrode encapsulationImplantable defibrillator electrode encapsulationStent clotting and closureCatheter thrombosis, infectionContact lens discomfort and eye injuryIntraocular lens 25%-50% reoperation rate

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Metals Polymers Ceramics Biologicalmaterials

e.g. titanium, e.g. UHMWPE, e.g. alumina, e.g. chitin,stainless steel PMMA bioglass nacre

What is the similarity between all these widelydifferent materials?

They all have uncontrolled interfacial proteins!

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Protein adsorption consequences

Protein adsorption is energetically favourable

Protein adsorption influencesI activation of complementI blood clottingI bacteriaI cellsI implant functionality

Due to the adsorption the concentration of proteinsmay be a thousand fold higher compared to thesurrounding tissue fluid

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Protein adsorption

Proteins come into contact with the surface throughthese mechanisms:

I diffusionI thermal convectionI bulk flowI a combination thereof

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Modelling of protein adsorption

Concentration, speed and molecular size of theprotein are important variables when modellingadsorption

Fick II:

dndt

= C0(Dπt

)1/2 (1)

where n is concentration of proteins at the interphase,C0 is the concentration of proteins at bulk, D is thediffusion coefficient ja t is time

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Vroman effect

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Structure of proteins

[Griffths et al., 2000]

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Proteinin adsorption is affected by

I The size, charge, amphiphatic nature and stabilityof the protein

I The topography, charge, chemistry andmicrostructure of the surface

I The amount of the protein close to the surface

[Andrade et al., 1992]

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An example of the size effect

[Dee et al., 2002]

Fibrinogen (340 kDa) 703contacts/molecule

Albumin (67 kDa)77 contacts/molecule

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Example of the structural stability of theprotein

[Thevenot et al., 2008]

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The role of surface in protein adsorption

Topography Available area for adsorptionChemistry Molecular interactionWettability Hydrophobic interaction strongerHeterogenity Wider scale of

possible interactionsCharge Attraction &repulsionElasticity Possible effects on conformation

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Proteins affect surface

Proteins may damage the surface of a biomaterialI Crevice corrosionI Secretions of cellsI Calcium ions

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Brainstorming II

What kind of issues you need to consider whenyou select a biomaterial for an implant?



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Criteria for the selection of biomaterials

Criteria for the selec-tion of biomaterials

Physicalproperties

Biologicalfixation

propertiesCan be

purified, fa-bricated and

sterilizedeasily

Maintainsthe desiredpropertiesin vivo for

the requiredperiodof time

Does notinduce

undesirablehost-implant

reactions

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Criteria for the selectionof biomaterialsMuddy cards

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Next time: Properties of materials

I Why are metals, ceramics and polymers different?I Bulk properties and their relevance for implantsI Surface properties and their relevance for

implants

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Seminar topics

Find a pair and choose your topic at MyCourses.

I Smart metals as biomaterials ( Pair 1)I Smart polymers as biomaterials ( Pair 2)I Recent tissue engineering applications (Pair 3)I Biomaterials controlling neurogenesis (Pair 4)I Predicting implant integration with in vitro

experiments (Pair 5)I Biocompatibility challenges in brain (Pair 6)I In vitro testing platforms e.g. artificial lung (Pair 7)I Tissue-integrated sensor (Pair 9)I Non-fouling sensors (Pair 10)I Biomaterials in stimulating biolectrodes (Pair 11)

You may also suggest a topic of your own.


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References

Andrade, J. D., Hlady, V., and Weibel, A. P. (1992).Adsorption of complex proteins at interfaces.Pure & Appl Chem, 64:1777–1781.

Dee, K. C., Puleo, D. A., and Bizioz, R., editors (2002).An Introduction to Tissue-Biomaterial Interactions.Jon Wiley & Sons.

Griffths, A. J. F., Miller, J. H., T.Suzuki, D., Lewontin, R. C., and Gelbart, W. M. (2000).An Introduction to Genetic Analysis.W. H. Freeman and Company.

Ratner, B. D., Hoffman, A. S., Schoen, F. J., and Lemons, J. E., editors (2013).Biomaterials Science An Introduction to Materials in Medicine.Elsevier.

Thevenot, P., Hu, W., and Tang, L. (2008).Surface chemistry influences implant biocompatibility.Curr Top Med Chem, 8(4):270–280.

Williams, D. F. (2008).On the mechanisms of biocompatibility.Biomaterials, 29(20):2941–2953.

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Course book:

I Introduction - Biomaterials ScienceI A History of BiomaterialsI Chapter I.1.1 - Introduction: Properties of

MaterialsI Chapter II.1.2 - Adsorbed Proteins on

BiomaterialsI Chapter III.1.2 - Sterilization of Implants and

Devices

introduction to biomaterials science - aalto to biomaterials science emilia peltola, dsc 7.9.2015. 4...

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