Tissue Engineering at FCT/UNL
Jorge Car valho Silva
[email protected]
GREAT - Grupo de Engenharia de Tecidos
great.cefitec.df.fct.unl.pt
Tissue Engineering
Tissue Engineering is a branch of Biomedical Engineering that
combines
cells, materials and growth factors
using the methods of engineering and the knowledge of the life and
exact sciences for the development of biological substitutes to
improve or replace the function of damaged or missing organs or
tissues.
2
Tissue Engineering: Why?
http://organdonor.gov/about/data.html
3
TO
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TO
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Tissue Engineering: the Future
4
Tissue Engineering: a multidisciplinary effort
Materials
Science
Chemical
Engineering
Genomics
Molecular
Biology
Cell
Biology
Clinicians
Biochemistry
Computational
Biology
Robotics
5
GREAT
Grupo de Engenharia de Tecidos / Tissue Engineering Group
Blood Vessels
Skin
Research subjects
Bone
Spinal Cord
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Once upon a time...
3) * Nanofibre tube boosts nerve regeneration *
Researchers at the National University of Singapore have used polymer nanofibre
tubes to promote nerve regeneration. The tubes acted as guidance channels,
enabling nerves to regrow in 45% of a test sample.
See http://nanotechweb.org/articles/news/3/12/6
7
8
2007
Fibers electrospun for different
needle tip-collector distances
Fibers electrospun at different feed rates
A systematic study of solution and processing parameters on nanofiber
morphology using a new electrospinning apparatus,
J. Nanosci. Nanotechnol.9, 3535-3545 (2009).
Henriques, C; Vidinha, R.; Botequim, D.; Borges, J.P., Silva, J.C.
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Nanofibres from chitosan-cellulose acetate blends for tissue
engineering applications, Ricardo Vidinha, July 2008.
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Chitosan nanofibre scaffolds for application as skin
substitutes, David Botequim, December 2009
Influence of relative humidity on the electrospinning of the blend
CS:PEO 1:1: 40%, 45%, 50% e 55%. Magnification: !5000.
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Research subjects
Tissue Engineering and Regenerative Medicine
Application of the principles of biology and engineering to the
development of functional substitutes for damaged tissue
Deep burns are one of the most traumatic situations for the human body
Skin
Chronic, difficult to heal wounds are a major clinical problem
Both substantially affect quality of life of patients
No satisfactory and complete therapies
pressure ulcer
3rd degree burn
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Skin
Biomimetic approach:
Porous, flexible, multilayered structure
Comprising both dermal and epidermal (i.e. full skin) equivalents
Use of autologous cells (from the patient himself)
Synergistic approach:
Mix of natural and synthetic polymers
Bioactive materials, wound healing accelerators
Including anti-bacterial agents
Skin2: a biosynthetic second skin,
engineered to treat severe burn
wounds
PTDC/SAU-BMA/109886/2009
160 k!
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Skin
Development of biomimetic scaffolds as skin substitutes for the
treatment of burns.
Susana Gomes
Electrospinning
Collector
Syringe Solution Needle
Jet
Syringe pump
3T voltage power supply
High
Taylor’s cone
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Skin
Development of biomimetic scaffolds as skin substitutes for the
treatment of burns.
Susana Gomes
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Skin
Estudo e optimização da técnica de Fiação Húmida para a produção de
Microfibras de Quitosano. André Delgado, 2011
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Skin
Development of hybrid nano+micro fibrous matrices of chitosan for
the treatment of extensive skin wounds
Ana Espiga Machado
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Skin
Matrizes de Policaprolactona e Quitosano para aplicação em
Engenharia de Tecidos.
Valdir Tavares, 2011
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Research subjects
Tissue Engineering and Regenerative Medicine
Application of the principles of biology and engineering to the
development of functional substitutes for damaged tissue
Blood Vessels
Syringe
needle
High Voltage
Power Supply
Syringe
needle
High Voltage
Power Supply
Syringe
pump
Syringe
pump
Rotating and translating
grounded collector
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Construção
e
caracterização
de um colector rotatório para a
:9<B/6D5)F5)
V[CE!
produção
850/865D)
N!&&) de nanofibras alinhadas
Pedro Alexandre Marques Anacleto, 2008
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L)
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Research subjects
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Tissue Engineering and Regenerative Medicine
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development of functional substitutes for damaged tissue
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Bone
+,)
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Bone
P.Q. Franco et al. / Materials Letters 67 (2012) 233–236
235
Electrospun hydroxyapatite fibers from a simple sol–gel system
Franco et al. / Materials Letters 67 (2012) 233–236
Patrícia Franco,P.Q.2009
235
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Fig. 1. SEM images of the membranes a) 18-50 and b) 18-100, after sintering and respective diameters distribution.
non-sintered sample presents the bands already mentioned for
membranes produced from PVP solutions in ethanol/water mixtures
are equal to the ones presented in Fig. 3. PVP presents the characPVP as well as the band at 3800 cm −1 resulting from the symmetric
−1
corresponding
teristic bands at 2950, 1656, 1459 and 1288 cm
deformation of the hydroxyl groups present in HA. The first indica1. SEM
images
of the
membranes
18-50 respectively
and b) 18-100, after
respective
distribution.
to C–H, Fig.
C=O,
C–H
(cyclic
groups)
anda) C–N,
[20].sintering
The andtion
of thediameters
formation
of an apatitic structure is a wide band at about
1000 cm −1 and 1100 cm −1. The bands at 960–965 cm −1 and at
560–601 cm −1 correspond to the symmetric stretching of the PO43−
non-sintered sample presents the bands already mentioned for
membranes produced from PVP solutions in ethanol/water mixtures
ions. We can observe the presence of the main peak of the phosphate
are equal to the ones presented in Fig. 3. PVP presents the characPVP as well as the band at 3800 cm −1 resulting from the symmetric
group identified in the region in between 1100 cm−1 and 960 cm−1,
teristic bands at 2950, 1656, 1459 and 1288 cm − 1 corresponding
deformation of the hydroxyl groups present in HA. The first indicato C–H, C=O, C–H (cyclic groups) and C–N, respectively [20]. The
tion of the formation of an apatitic structure is a wide band at about
1000 cm −1 and 1100 cm −1. The bands at 960–965 cm −1 and at
3PO
560–601 cm −1 correspond to the symmetric stretching of the PO43−
4
32PO4
CO
ions. We can observe the presence of the main peak of the phosphate
3
group identified in the region
inOH
between 1100 cm−1 and 960 cm−1,
OH
Bone
Production of three dimensional Poli(e-Caprolactone) and
Hidroxiapatite porous scaffolds for bone regeneration
Sara Ferreira, 2010
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3-
PO
PO4
3
OH OH
18-100
As-spun
4
3-
2-
CO
18-100
o
Ts= 700 C
CO
OH
18-100
o
Ts= 700 C
2-
CO
OH
3
PVP
C-N
C-H
18-100
As-spun
C-H
C=O
PVP
3500
3000
2500
2000
1500
1000
500
Wavenumber / cm-1
C-N
C-H
Fig. 2. Diffractograms of the membrane 18-100, sintered at 500 °C, 600 °C and 700 °C.
Fig. 3. FTIR spectra of a PVP film and of membrane 18-100 before and after sintering at
700 °C.
C-H
Hot pressing / porogen leaching
3500
C=O
Fig. 2. Diffractograms of the membrane 18-100, sintered at 500 °C, 600 °C and 700 °C.
3000
2500
2000
1500
1000
500
Wavenumber / cm-1
SaOs2 - Osteoblasts
Fig. 3. FTIR spectra of a PVP film and of membrane 18-100 before and after sintering at
700 °C.
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Bone
Production of composite chitosan/
hydroxyapatite microfibers using
the wet-spinning method
Liquid Crystalline Inverse Opals:
New Bone like Assemblies for
Tissue Engineering
Carlos João, 2010
Carlos João, 2014
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Research subjects
Tissue Engineering and Regenerative Medicine
Application of the principles of biology and engineering to the
development of functional substitutes for damaged tissue
Spinal Cord
Development of
biodegradable supports
for the regeneration of
neuronal tissue.
Ana Luísa Marques,
December 2011.
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Número de células aderente/membrana
Development of biodegradable supports for the regeneration of neuronal
tissue. Ana Luísa Marques, December 2011.
60000
50000
CS alinhado
40000
30000
20000
CS desalinhado
PCL alinhado
10000
0
com PDL/Lam sem PDL/Lam sem PDL/Lam
CS alinhado
Comprimento dos axónios / !m
0.120
0.100
0.080
CS alinhado
Controlo CS desal.
0.060
0.040
0.020
0.000
Com
Com
PDL/Lam PDL/Lam
Sem
PDL/Lam
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Wound dressings
Development of a wound dressing based on nanofibers of polyvinilpirrolidone
containing povidone-iodine. Andreia Fernandes. February, 2011.
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Incorporação de nanopartículas de prata em matrizes de nanofibras
de polivinilpirrolidona e avaliação do seu potencial antibacteriano.
Rita Morais Rosa, Maio 2012
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Biodegradable occlusive membranes for guided
tissue regeneration or guided bone regeneration
Composite membranes
of poly(e-caprolactone)/
hydroxyapatite for
dental applications
João Martins, 2011
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Biodegradable occlusive membranes for guided
tissue regeneration or guided bone regeneration
Chitosan/poly(e-caprolactone) membranes
for dental applications
Mafalda Fernandes, 2011
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Entrepreneurial projects
NovaTissue
Assembly of 3D porous structures incorporating a pre-vascular network
NanoSutures
High-tech sewing
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People – Staff and collaborators
Members
Célia Henriques, José Luís Ferreira
Collaborators from FCT/UNL
João Paulo Borges, Carmo Lança (Materials Science)
Ilda Sanches, Alexandra Fernandes (Life Sciences)
Pedro Coelho (Mechanical Engineering)
Isabel Catarino, Grégoire Bonfait, Pedro Vieira (DF)
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People – Staff and collaborators
External Collaborators
Maria Angélica Roberto
Hospital “S. José”, Burns Intensive Care Unit & Plastic and Reconstructive Surgery, Director
Manuela Mafra
Hospital “S. José”, Anatomo-Pathology service
Harshad Navsaria
Barts and the London School of Medicine and Dentistry, Queen Mary, University of London
Maria Gabriela Rodrigues, Gabriel Martins
Faculty of Sciences, University of Lisbon
Dora Brites, Adelaide Fernandes, Alexandra Brito, Ana Sofia Falcão
Faculty of Farmacy, University of Lisbon
Ana Isabel Silva
Faculty of Engineering, Portuguese Catholic University
Marise Almeida
Faculty of Dentistry, University of Lisbon
Sofia Prata
Ceramed
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MSc and PhD Students
MSc
Ricardo Vidinha, Pedro Anacleto, David Botequim, Patrícia Franco,
Rita Maduro, Sara Ferreira, Carlos João, Andreia Fernandes, Ana
Marques, João Martins, Mafalda Fernandes, Joana Fonseca, Valdir
Tavares, Rita Carvalho, Rita Rosa; Cláudia Aragão, Ana Rosa, Sara
Costa, Luís Martins, Joana Vasconcelos
PhD
Ana Espiga Machado, Susana Gomes, Carlos João, Ana Sofia Pedrosa
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What Will Be the 10
Hottest Jobs?
May 22, 2000
1 TISSUE ENGINEERS
With man-made skin
already on the market and
artificial cartilage not far
behind, 25 years from now
scientists expect to be
pulling a pancreas out of a
Petri dish. Or trying,
anyway. Researchers have
successfully grown new
intestines and bladders
inside animals' abdominal
cavities, and work has
begun on building liver,
heart and kidney tissue.
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Tissue Engineering at FCT/UNL
Jorge Car valho Silva
Obrigado
GREAT - Grupo de Engenharia de Tecidos
CeFITec / DF / FCT / UNL
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Tissue Engineering at FCT/UNL Jorge Carvalho Silva GREAT