Tissue Engineering at FCT/UNL

Jorge Carvalho Silvajcs@fct.unl.pt

GREAT - Grupo de Engenharia de Tecidosgreat.cefitec.df.fct.unl.pt

Tissue Engineering

Tissue Engineering is a branch of Biomedical Engineering that

combines

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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.

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Tissue Engineering: Why?

http://organdonor.gov/about/data.html

TODAY

TOMORROW

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Tissue Engineering: the Future

Tissue Engineering: a multidisciplinary effort

Chemical

Engineering

Molecular

Biology

GenomicsRobotics Computational

Biology

Materials

ScienceCell

Biology

Clinicians Biochemistry

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GREATGrupo de Engenharia de Tecidos / Tissue Engineering Group

Skin

Spinal Cord

Research subjects

Bone

Blood Vessels

Once upon a time...

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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

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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.

2007

Fibers electrospun at different feed rates

Fibers electrospun for different needle tip-collector distances

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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

SkinDeep burns are one of the most traumatic situations for the human body

Chronic, difficult to heal wounds are a major clinical problem

Both substantially affect quality of life of patients

No satisfactory and complete therapies

3rd degree burn

pressure ulcer

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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!

Skin

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Syringe pump

High voltage power supply

Syringe Solution Needle JetCollector

Taylor’s cone

Electrospinning

3T

Development of biomimetic scaffolds as skin substitutes for the treatment of burns.

Susana Gomes

Skin

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Development of biomimetic scaffolds as skin substitutes for the treatment of burns.

Susana Gomes

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

Rotating and translating grounded collector

Syringe pump

Syringe pump

Syringe needle

Syringe needle

High Voltage Power Supply

High Voltage Power Supply

Construção e caracterização de um colector rotatório para a produção de nanofibras alinhadas

Pedro Alexandre Marques Anacleto, 2008

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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

Bone

membranes produced from PVP solutions in ethanol/water mixturesare equal to the ones presented in Fig. 3. PVP presents the charac-teristic bands at 2950, 1656, 1459 and 1288 cm!1 correspondingto C–H, C=O, C–H (cyclic groups) and C–N, respectively [20]. The

non-sintered sample presents the bands already mentioned forPVP as well as the band at 3800 cm!1 resulting from the symmetricdeformation of the hydroxyl groups present in HA. The !rst indica-tion of the formation of an apatitic structure is a wide band at about1000 cm!1 and 1100 cm!1. The bands at 960–965 cm!1 and at560–601 cm!1 correspond to the symmetric stretching of the PO4

3!

ions. We can observe the presence of the main peak of the phosphategroup identi!ed in the region in between 1100 cm!1 and 960 cm!1,

Fig. 1. SEM images of the membranes a) 18-50 and b) 18-100, after sintering and respective diameters distribution.

Fig. 2. Diffractograms of the membrane 18-100, sintered at 500 °C, 600 °C and 700 °C.

3500

PVP

18-100As-spun

Wavenumber / cm-1

PO3-

4

PO3-

4

CO2-

3

CO2-

3

OH

OH OH

C-H

C=OC-H

C-N

18-100

Ts= 700 oC

3000 2500 2000 1500 1000 500

Fig. 3. FTIR spectra of a PVP !lm and of membrane 18-100 before and after sintering at700 °C.

235P.Q. Franco et al. / Materials Letters 67 (2012) 233–236Bone

Electrospun hydroxyapatite fibers from a simple sol–gel system

Patrícia Franco, 2009

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membranes produced from PVP solutions in ethanol/water mixturesare equal to the ones presented in Fig. 3. PVP presents the charac-teristic bands at 2950, 1656, 1459 and 1288 cm!1 correspondingto C–H, C=O, C–H (cyclic groups) and C–N, respectively [20]. The

non-sintered sample presents the bands already mentioned forPVP as well as the band at 3800 cm!1 resulting from the symmetricdeformation of the hydroxyl groups present in HA. The !rst indica-tion of the formation of an apatitic structure is a wide band at about1000 cm!1 and 1100 cm!1. The bands at 960–965 cm!1 and at560–601 cm!1 correspond to the symmetric stretching of the PO4

3!

ions. We can observe the presence of the main peak of the phosphategroup identi!ed in the region in between 1100 cm!1 and 960 cm!1,

Fig. 1. SEM images of the membranes a) 18-50 and b) 18-100, after sintering and respective diameters distribution.

Fig. 2. Diffractograms of the membrane 18-100, sintered at 500 °C, 600 °C and 700 °C.

3500

PVP

18-100As-spun

Wavenumber / cm-1

PO3-

4

PO3-

4

CO2-

3

CO2-

3

OH

OH OH

C-H

C=OC-H

C-N

18-100

Ts= 700 oC

3000 2500 2000 1500 1000 500

Fig. 3. FTIR spectra of a PVP !lm and of membrane 18-100 before and after sintering at700 °C.

235P.Q. Franco et al. / Materials Letters 67 (2012) 233–236

Bone

Production of three dimensional Poli(e-Caprolactone) and Hidroxiapatite porous scaffolds for bone regeneration

Sara Ferreira, 2010

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Hot pressing / porogen leaching

SaOs2 - Osteoblasts

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Bone

Production of composite chitosan/

hydroxyapatite microfibers using

the wet-spinning method

Carlos João, 2010

Liquid Crystalline Inverse Opals:

New Bone like Assemblies for

Tissue Engineering

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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Development of biodegradable supports for the regeneration of neuronal

tissue. Ana Luísa Marques, December 2011.

Wound dressings

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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

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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Chitosan/poly(e-caprolactone) membranes for dental applications

Mafalda Fernandes, 2011

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Biodegradable occlusive membranes for guided

tissue regeneration or guided bone regeneration

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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 CollaboratorsMaria 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

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.36

Tissue Engineering at FCT/UNL

Jorge Carvalho Silva

GREAT - Grupo de Engenharia de Tecidos

CeFITec / DF / FCT / UNL

Obrigado