Soft bone cement for brittle bone

Cecilia Persson1, Alejandro López1,2, Malin Nilsson2

1 Department of Materials Science and Engineering, Uppsala University, Sweden. 2 Inossia AB, Sweden.

Background

0

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Standardcement

Softcement Bone

Averageelasticm

odulus

(MPa

)

0102030405060708090

100

Standardcement

Softcement Bone

Averagecompressive

strength(M

Pa)

newfractures40%Success

60%

Nonadjacentfractures33%

Adjacentfractures67%

Incidenceofosteoporosisinadults>50yearsoldworldwide

%PatientsVertebralaugmentation %fractures

Standardcementtoostiff!

Controlling the mechanical properties of bone cement using

cement softener

0200400600800

100012001400160018002000

0.0 0.2 0.4 0.6 0.8 1.0 1.2

Elasticm

odulus(M

Pa)

%CementSoftener

Standardcement

mediumstiffnesscement

softcement

Handling properties

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5

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30

Standardcement Softcement

settingtim

e(m

in)

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Standardcement Softcement

doughingtime(m

in)

0

10

20

30

40

50

60

70

Standardcement Softcement

maxim

umte

mpe

rature(°C)

Slightlylongersettingtimeforsafeinjectability

Lowsettingtemperaturefor

reducedriskoftissuenecrosis

Behavior and injectability Polymerizationtemperatureatvariousroom

temperatures

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25

50

75

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125

150

0 2 4 6 8 10 12 14 16 18 20 22 24

Force(N)

Time(min)

Standardcement(1.5mm/min)

Softcement(1.5mm/min)

Standardcement(5mm/min)

Softcement(5mm/min)

Easierandsaferinjectabilityattwodifferentspeeds

Cohesion StandardcementSoftcement

Nosignificantdifferenceincementspread(sphericity)=

goodcohesion!

Mechanical properties

24h 24h2w 2w4w 4w0

500

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Standardcement Softcement

Elasticm

odulus(M

Pa)

24h 24h2w 2w4w 4w0

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120

Standardcement Softcement

Compressivestrength(M

Pa)

Rodent in vivo model

Representativehistologicalsectionsoftissueexplantsfrom1,4and12weeks,stainedwithhematoxylinandeosin(ISO10993-6).•  Notoxicreaction•  Nodifferenceintissueresponsebetweenstandardandsoftcements•  Noabnormaltissueorganizationapartfromnecessarywoundhealing

RepresentativeCT-scansofimplantsinvivoandexvivo.Fiveimplantsoutofeightareobservedinthis

image.

Sprague-Dawleyratsharvestedat1,4and12weeks•  8implants/animal•  Histology•  Flowcytometry

Rodent in vivo model

•  No statistical differences (p > 0.05) were found between the populations of immune cells present in the tissue surrounding the different materials, indicating that there was no significant differences in the immune response to the modified PMMA cements compared to the base cement.

•  The leukocyte population decreased between 1-week and 12-week (p=0.04). •  The granulocyte population decreased between 4-week and 12-week (p=0.009). •  The macrophage population showed no significant change in presence over time.

Sheep in vivo model NAMSA(Lyon):7sheep:defectsizeØ=4mmandh=9-12mmharvestedat4and12weeks8implants/animalImplantedinthebone

A. B.

LEFT

C. D.

RIGHT

Thepurposeofthestudywastoevaluate:•  thelocaltissueeffects•  thedegradation•  theperformance

Sheep in vivo model X-Rayimagesofmodifiedcement(AandB)andcontrol(CandD)at4weeks

Tissueresponseanalysedinregionofinterest

Sheep in vivo model A-modifiedcementB-control.C-modifiedcementat4weeksD-controlat4weeksE-modifiedcementat12weeksF-controlat12weeksBT:Bonetissue(pink),IG:Implantgranules(blackdots)I:Implant(white)FB:fibroustissue(navyblue)BM:Bonemarrow(grey)

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Test Control Test Control

ImplantAreaDensity(%)LacunaeAreaDensity(%)FibrousAreaDensity(%)BoneAreaDensity(%)

4weeks 12weeks

Conclusions •  Low stiffness of soft cement matches trabecular bone

•  Low setting temperature making it a safer product

•  Longer injection time giving improved injectability and safer handling

•  Easy to mix and use, does not alter known mixing procedure for bone cements •  No toxic reaction, no significant difference in tissue or immune response, no delayed immune response,

and generally biocompatible in rodent and sheep in vivo model •  Bone healing response observed around the soft cement was similar to that noted around the control

over time, both qualitatively and histomorphometrically.

Conclusions

The new cement showed safe biological response in combination with more adequate mechanical properties for osteoporotic bone, making it a promising material for improved outcomes of vertebroplasty in osteoporotic patients.

Acknowledgements •  MedTech4Health•  VINNOVA(VINNMER2010-02073)•  EU(FP7-PEOPLE-2010-268134)

Contact:Cecilia.Persson@angstrom.uu.se