Tailored Bioabsorbable Implants and Scaffolds

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    Tailored bioabsorbable implants and scaffolds

    for biomedical and tissue engineering

    applications

    Minna Kellomki

    Professor, Dr Tech, FBSE

    BioMediTech

    and

    Department of Electronics and Communications Engineering

    Tampere University of Technology, Finland

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    History of biomaterials research in Finland

    Tekes review 289/2012, p. 63

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    3

    4.9.2013

    1st in the world innova

    tions and products

    1st in the world several surgical implant familiesintroduced to clinical studies, examples:

    Ultra-high strength pins and screws for bonefracture fixation

    Membranes for guided tissue regeneration

    Arrows for closing of knee meniscus ruptures

    Stents for urological and gastro-enterologicalapplications

    Malleable plates for craniomaxillofacial, spineand thoracic surgical applications

    Antibiotic releasing screws for prophylacticapplications

    Bioreconstructive scaffolds for finger and toejoint regeneration

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    Biomaterials research areas

    Leader: Minna Kellomki Prof, Dr Tech, FBSE

    Processing, microstructures and properties of:

    Bioabsorbable, synthetic polymers

    Hydrogels

    Modified natural organic materials

    Polymer-ceramic composites

    Bioceramics and bioactive glasses

    Development of:

    Surgical implants and implantable measuring devices Scaffolds for tissue engineering

    Drug releasing biomaterials

    Biocompatible surfaces and electrical properties of

    biomaterials

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    Advanced Tissue Regeneration Technology;Osteopromotive Composite Scaffolds and Cellular

    Response with Human Adipose Stem Cells

    KURKO

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    Requirements for TE-scaffold technology

    Requirements for a tissue

    engineering scaffold:

    Biocompatible

    Optimal pore size

    Interconnected pore

    structure

    Bioabsorbable

    Requirements for a technology

    transfer from the lab to the clinics:

    Better functionality or activity

    compared to the existingtechnology

    High manufacturing rate and

    yield

    Low manufacturing costs

    Easy to use

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    Scaffold structures

    PLCL: Porosity up to 70 %

    Average pore size 500-1000 m

    Max pore size 1300-2300 m

    PLCL--TCP 40 wt-%:

    Porosity up to 70 %

    Average pore size 300-800 m

    Max pore size 600-2300 m

    PLCL--TCP 60 wt-%:

    Porosity up to 60 %

    Average pore size 300-600 m

    Max pore size 600-1500 m

    Scaffold + water

    Scaffold phase Water phase

    Pore interconnectivity 98-99 %

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    In vitro cytocompatibility

    Seeding with human

    adipose stem cells(660 cells/ mm3)

    Cell attachment and

    viability

    Live/dead-fluorescent probes

    Cell proliferation

    Quantitative DNA analysis(CyQuant)

    Early stage osteogenic

    differentiation

    Quantitative alkaline

    phosphatase activity

    Adipose stem cells have

    been used successfully for

    clinical bone regeneration

    [2,3]

    [2] Mesimaki K, et al. Int J Oral Maxillofac Surg, 2009.[3] Thesleff T, et al. Neurosurgery, 2011.

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    Conclusions

    ScCO2

    -processing enables effective manufacturing of

    porous and biodegradable scaffolds without harmful

    solvents

    The scaffolds mechanical properties enable cyclic loading

    and easy tailoring of the scaffolds to the desired shape

    PLCL 70/30 -TCP scaffolds support the attachment

    and stimulate the proliferation of hASCs

    Preliminary results show also that thescaffolds induce the early osteogenic

    differentiation

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    The Team and Acknowledgements

    Scientific team:

    Tampere University of TechnologyProfessor Minna Kellomki

    Kaarlo Paakinaho

    Niina Ahola

    Professor Mika Valden

    Leena Vuori

    Professor Jari Hyttinen

    Markus Hannula

    Tampere University

    Doc. Susanna Miettinen

    Suvi Haimi

    Laura Tirkkonen

    Sanna Huttunen

    Aalto UniversityProfessor Jukka Seppl

    Laura Elomaa

    International collaboration with:

    Professor Dirk Grijpma, University of Twente, The Netherlands

    Professor Marcy Zenobi-Wong, ETH Zrich, Switzerland

    Professor Maria Rita Passos-Bueno, University of Sao Paulo, Brazil

    Funding and collaboration:

    Industrial collaboration:

    The Finnish Funding Agency for

    Technology and Innovation

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    Biomaterials for regenerative

    medicine

    -

    Human Spare Parts projecthttp://www.biomeditech.fi/research/human_spare_parts_program.php

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    In the picture 1990s human spare parts

    Scientific teams:

    Tampere University of Technology

    Professor Minna Kellomki (Biomaterials)

    Professor Jari Hyttinen (Imaging and image analysis)

    Ptofessor Jukka Lekkala (Biosensors and measurements)

    Professor Pasi Kallio (Biomimetic environments)

    Tampere University

    Doc. Susanna Miettinen (Adipose stem cells)

    Doc. Susanna Narkilahti (Neuro)

    Doc. Heli Skottman (Ophthalmology)

    Doc. Katriina Aalto-Setl (Cardiac cells and tissues)

    Main funding:

    The Finnish Funding Agency for

    Technology and Innovation

    http://www.biomeditech.fi/research/human_spare_parts_program.php

    http://www.biomeditech.fi/research/human_spare_parts_program.phphttp://www.biomeditech.fi/research/human_spare_parts_program.phphttp://www.biomeditech.fi/research/human_spare_parts_program.phphttp://www.biomeditech.fi/research/human_spare_parts_program.php
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    134.9.2013

    Biomaterials research themes in HSP

    1. Fibers and 2D & 3D textiles2. Hydrogels and functionalization of

    materials

    3. Biodegradable sensors

    Application areas:

    1. Regenerative medicine

    2. Cell culture surfaces and devices

    3. Material development and characterization

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    Melt-spun biodegradable fibers

    Melt processing of biodegradable polymers

    - Design and manufacturing of the equipment and

    tools

    - Optimization of parameters for spinning of fibers

    Coarse Fine Ultra fine Nano & Hollow fibers

    > 100 m 100-30 m 30-1 m < 1 m > 60 m

    Slide by Ville Ell / TUT BME

    4.9.2013

    F fib diff t

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    From fibers different

    textile structures

    From fibers production of multiple textile structures

    from textiles scaffolds and implants

    e.g. Knits Braids Non-wovens Wovens

    Slide by Ville Ell / TUT BME

    4.9.2013

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    PLA96 + fibrin hybrids

    Tschoeke B et al. Tissue Engineering 2009Koch et al, Biomaterials 2010

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    Two photon polymerization

    - structures and functionalization

    - (additional partner: VTT)

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    (a) (b) (c)

    Neurocages (2PP)

    Protein structures: BSA (left) and avidin (right) (2PP)

    Miniaturized trabecular

    bone replica (2PP)

    Designed scaffold; close-up of nanostructure; cultured

    ASCs(2PP)

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    Embedded measuring circuits

    -1.5

    -1

    -0.5

    ShiftofFrequency(MHz)

    PCL 2,40 mm

    PLCL 2,09 mm

    PDMS 2.19 mm

    - Measuring circuit embedded inside polymer foils

    - Distant reader system- Detection of water diffusion into the polymer

    structure

    Salpavaara et al, 2012

    - We can use this information to e.g.- Understand material behavior

    more deeply

    - Enhance material selection

    process for applications

    - By improving models how

    polymers degrade

    (collaboration prof Pan,

    Univ Leicester)

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    Biomaterial requests in HSP

    Permanent > temporary

    Biostabile bioabsorbable > bioactive

    Replacement - repair > tissue engineering

    Solid -> porous

    Hard/rigid & soft/flexible & hydrogel/gel

    2D & 3D

    Macro & micro & nano

    Basic research

    > R&D

    > commercialization/products19

    4.9.2013

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