Biopharmaceuticals

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RCSI Tissue Engineering Research Group
Institute of Biomedical Sciences- UFRJ
Research Initiative
Fergal J. O’Brien, PhD
Professor of Bioengineering & Regenerative Medicine
Deputy Director of Research, RCSI
Head of Tissue Engineering Research Group
Deputy Director, Advanced Materials & BioEngineering Research (AMBER) Centre
Chair of Executive Committee, Trinity Centre for Bioengineering
Dept. of Anatomy, Royal College of Surgeons in Ireland
Trinity Centre for Bioengineering, Trinity College Dublin
AMBER, RCSI & TCD
@TissueEngDublin
Biomimetic ECM-derived biomaterials provide an
opportunity to alleviate problems with traditional
techniques to replace diseased or damaged organs
• Transplantation/allografting
(lack of donors/donor tissue)
• Autografting (lack of tissue)
• Permanent prosthesis (not permanent)
Research Focus
• Biomaterial scaffolds
- Collagen-glycosaminoglycan/elastin/fibrin
- Collagen-ceramic composites
- Chitosan, alginate, fibrin & hyularonic acid hydrogels
• Cells
-
Tissue-derived mature cells
Bone marrow-derived mesenchymal stem cells
Neural stem cells (OECs)
Adipose stem cells
Amniotic fluid-derived stem cells
Cardiac stem cells
Limbal stem cells
• Cell signalling
- Bioreactors & Mechanobiology
- role of biophysical stimuli in regulating stem cell
differentiation and tissue formation
- Growth factors (controlled release)
- Nucleic acids: pDNA/ siRNA/ microRNAs
- Platelet-rich plasma
Bone
Angiogenesis
Cartilage
+GFs
Cornea
+Genes
Nerve
+ Co-cultures
Respiratory
+ Hypoxia
+ Flow perfusion
Cardiovascular
+Endochondral
Applications
Ossification
HydroxyColl™
A Viable Alternative to Autogenous Bone
Patent: WO 2008/096334
Enterprise Ireland Commercialisation Fund
POC PC/2007/331 & CFTD TD/2007/112
ChondroColl™
Hyaline Cartilage Regeneration
Defect Site
Empty
Empty
Defect
Enterprise Ireland Commercialisation Fund
POC PC/2005/226 & CFTD TD/2009/104
ChondroColl
ChondroColl
Restoration of hyaline cartilage on
articular surface following implantation
with ChondroColl
Intertrade Ireland SEEDCORN
Business Competition
`Best Emerging Company’
Regional Winner, Nov. 2011
June, 2012
Scaffolds as Delivery Systems
- Cells
- Tissue
- Genes (non-viral technologies)
- Growth factors
Platelet-rich plasma
Scaffolds for controlled, sustained, transient release
Collagen Scaffolds as Drug Delivery Systems
(A) Controlled release of BMP from a collagen-based scaffold at two different rates using two different types
of polymeric microcapsules (B) SEM image of growth factor-containing microparticles embedded in the
collagen matrix of the scaffold
EU and PCT Patent (Pending): O'Brien FJ, Lopez-Noriega A, Quinlan E, Partap S, Kelly H, Cryan SA.
Application number: EP12188511.5 (Priority Date, October 15, 2012)
López-Noriega et al. (2014) Advanced Healthcare Materials. 3(6):854-9.
Lopez Noriega et al. (2014) Journal of Controlled Release 10;187:158-66
Quinlan et al. (2015) Journal of Controlled Release Jan 28;198C:71-79
Gene-activated Scaffolds
In Vivo
Healing
Stem cell
Nano particle + gene
Transfected Cell
Cell-based manufacture
of therapeutic
Tierney et al. (2012) Journal of Controlled Release 158(2):304-11
Tierney et al. (2013) Journal of Controlled Release 165(3):173-82
Tierney et al. (2013) Organogenesis. 9(1). 158-164
Raftery et al. (2013) Molecules 18(5):5611-47.
Curtin et al. (2015) Advanced Healthcare Materials. [Epub ahead of print]
Clinical
Collaborators
University of Sydney (Orthopaedics)
University of Aachen (Cadiovascular)
Lund University Hospital , Sweden (Orthopaedics)
Kyoto University (Oral and Maxillofacial Surgery)
Beaumont Hospital (Otolaryngology)
Cappagh Hospital (Orthopaedics)
Temple Street (Cranio/maxillofacial Surgery & ENT)
Mater Hospital (Otolaryngology)
Royal Victoria Eye & Ear Hospital (Ophthalmology)
Prof. David Little
Prof. Stefan Jockenhoevel
Prof. Magnus Tagil
Prof. Kazuhisa Bessho
Prof. Michael Walsh
Prof. John O’Byrne, Prof. Cathal Moran
Mr. Dylan Murray, Mr. Alec Blayney
Mr. Stephen Kieran
Prof. Conor Murphy, Dr. Billy Power
Industrial
Collaborators
Integra Life Sciences, NJ, USA
Marigot Ltd
SurgaColl Technologies
Dr. Simon Archibald
Dr. Denise O’Gorman,
Pat Forristal, John Gleeson
National
Academic
Collaborators
RCSI: School of Pharmacy
Molecular and Cellular Therapeutics
TCD: Trinity Centre for Bioengineering (TCBE)
UCD: Dept. of Anatomy
DCU: National Insitiute for Cellular Biotechnology
Dept. of Mechanical Engineering
NUI Maynooth: Institute of Immunology
Dept. of Biology
NUI Galway: National Centre for Bioengineering Science
REMEDI
University of Limerick: Mech Eng & MSSI
Drs. Sally Ann Cryan, Helena Kelly
Prof. Ray Stallings, Caroline Jefferies, Dr. Steve Kerrigan,
Dr. Danny Kelly, Dr. Conor Buckley
Prof. Veronica Campbell, Dr. Bruce Murphy
Dr. Paula Murphy
Profs. Jonathan Coleman, Ed Lavelle
Valeria Nicolosi, Graham Cross
Dr. Tom Flanagan
Prof. Martin Clynes, Dr. Finbarr O’Sullivan
Dr. Triona Lally,
Prof. Bernard Mahon
Dr. Shirley O’Dea
Prof. Peter McHugh, Dr. Laoise McNamara
Prof. Frank Barry, Prof. Tim O’Brien, Dr. Mary Murphy,
Dr. David Hoey
Colombia University: Dept. of Biomedical Engineering
Harvard Medical School: Dept. of Orthopaedic Surgery
Georgia Institute of Technology: Institute for Bioengineering
Wake Forest University: Institute for Regen Medicine
Colarado State University: Biomedical Engineering
Imperial College London: Biomaterials & Regen. Medicine
University College London: Inst of Orthopaedics
University of Adelaide: Bone and Joint Research Laboratory
Utrecht University: Dept. of Biomedical Engineering
Erasmus University, Rotterdam
Johannes Gutenberg Univ, Mainz: Institute of Pathology,
Federal University of Rio de Janeiro (UFUJ)
Prof. Chris Jacobs
Prof. David Mooney, Prof. Conor Walsh
Prof. Robert Guldberg
Prof. Shay Soker
Prof. Seth Donahue
Prof. Molly Stevens
Prof. Robert Brown
Prof. Nick Fazzalari, Dr. Ian Parkinson
Prof. Wim Hennink & Prof. Gert Storm
Prof. Gerjo van Osch, Drs. Eric Farrell & Y. Bastiaansens
Prof. James Kirkpatrick
Profs. Marcia Cury, Marcos Farina, Valeria de Mello Coelho
Dept. of Zoology
CRANN
International
Academic
Collaborators
Federal University of Rio de Janeiro
Institute of Biomedical Sciences-IBS
Rio de Janeiro- Brazil
Research Program in
Bioengineering and Cellular Therapies
Valeria de Mello Coelho
Associate Professor
Bioengineering and Cellular Therapies Research Program Coordinator
Laboratory of Immunophysiology, Head
Histotechniques Core Facility, Head
coelhova@histo.ufrj.br
Largest Federal University in Brazil
2nd oldest medical school in Brazil (founded in 1808)
Tradition in biomedical research
- Institute of Biophysics Carlos Chagas Filho, since 1940s
- Institute of Biomedical Sciences, since 1960s
Focus on engineering and biomedical sciences
(biochemistry, cell and tissue biology, neurobiology and stem cell research)
http://www.ufrj.br
Institute of Biomedical Sciences
Federal University of Rio de Janeiro
04 Undergraduate Teaching Programs:
Anatomy, Cell biology and Developmental biology, Histology and Pharmacology
(Attend all Undergraduate Courses in the biomedical field)
02 Graduate Programs:
Morphological Sciences
Pharmacology and Medicinal Chemistry
07 Research Programs:
Bioengineering and Cellular Therapies, Cell Biology, Cellular Differentiation, Drug
development, Glicobiology, Pharmacology and Inflammation, Neurosciences
http://www.icb.ufrj.br/
Bioengineering and Cellular Therapies Research Program
Mission: the conduction of scientific research aiming at the development
of new technologies for regenerative medicine
17 ICB INTRAMURAL MEMBERS
CLAUDIA BATISTA
FELIPE LEITE DE OLIVEIRA
HELIO DUTRA
JOSE BRITO
KATIA ARCANJO
KATIA CARNEIRO
LEONARDO RODRIGUES ANDRADE
MARCIA CURY EL-CHEIKH
MARCOS FARINA – DEPUTY
COORDINATOR
MARIA ISABEL DORIA ROSSI
MICHELLE BOTELHO
PAULO HENRIQUE R CASTRO
PAULO LOUZADA
RADOVAN BOROJEVIC
TATIANA SAMPAIO
VALERIA DE MELLO COELHO COORDINATOR
10 EXTRAMURAL MEMBERS
CHRISTINA TAKYIA- UFRJ- IBCCF
PRISCILLA FINOTELLI- UFRJ-FF
GLORIA SOARES- UFRJ/COPPE
LEANDRA BAPTISTA- UFRJ-XEREM
MONICA CALASANS MAIA-UFF
ALEXANDRE ROSSI-CBPF
ANDRE ROSSI- CBPF
MAURO GRANJEIRO – INMETRO
LEONARDO BOLDRINI- INMETRO
JACQUES WECKERMANN - INMETRO
ACHIEVEMENTS IN THE LAST 04 YEARS:
MORE THAN 200 PUBLICATIONS
1 BOOK and 12 BOOK CHAPTERS
03 PATENTS
31 PhD concluded
39 Masters concluded
08 post-doctoral concluded
23 INTERNATIONAL EXCHANGE
Visits/ Cooperation with France, Stanford
University, National Institutes of Heath, USA/
Organization of international meetings
BRAZILIAN FINANCIAL SUPPORT:
Program Overview: Research focus
Radovan Borojevic
UFRJ/INMETRO
Marcos Farina
UFRJ
José Mauro Granjeiro
UFF/INMETRO
Alexandre Rossi Monica Calasans
UFF
CBPF
AMABLE, PAOLA ROMINA ; TEIXEIRA, MARCUS VINICIUS ; CARIAS, ROSANA BIZON ; Granjeiro, José Mauro ; BOROJEVIC, RADOVAN .
Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton's jelly. Stem cell
research & therapy , v. 5, p. 53,2014.
ROSSI, AL. ; MOLDOVAN, SIMONA ; Querido, W ; ROSSI, A; WERCKMANN, J; ERSEN, OVIDIU ; FARINA, MARCOS. Effect of strontium
ranelate on bone mineral: Analysis of nanoscale compositional changes. Micron (Oxford. 1993) , v. 56, p. 29-36, 2014.
Baptista, LS. ; SILVA, KR. ; PEDROSA, CSG. ; AMARAL, R J.F.C. ; BELIZÁRIO, JV ; BOROJEVIC, R ; GRANJEIRO, JOSÉ MAURO . Bioengineered
Cartilage in a Scaffold-Free Method by Human Cartilage-Derived Progenitor Cells: A Comparison With Human Adipose-Derived
Mesenchymal Stromal Cells. Artificial Organs , v. 37, p. 1068-1075, 2013.
LOPEZ EO, MELLO A, SENDAO H, COSTA LT, ROSSI AL, OSPINA RO, BORGHI FF, SILVA FILHO JG, ROSSI AM. Growth of Crystalline
Hydroxyapatite Thin Films at Room Temperature by Tuning the Energy of the RF-Magnetron Sputtering Plasma ACS Appl Mater
Interfaces. 2013 Oct 9;5(19):9435-45.
Valiense, HB ; Alves, A.T.N.N. ; Mavropoulus, E ; TANAKA, M. ; ROSSI, A. M. ; BARRETO, M. ; Granjeiro, JM ; CALASANS-MAIA, M. D. . In
vitro and in vivo evaluation of strontium-containing nanostructured carbonated hydroxyapatite/sodium alginate for sinus lift in rabbits.
Journal of Biomedical Materials Research. Part B, Applied Biomaterials , v. 1, p. 1-9, 2015.
Felipe L Tatiana
Oliveira Sampaio
Isabel
Rossi
Helio
Dutra
Christina Leonardo Leandra Priscilla
Takiya Andrade Baptista Finotelli
Paulo H Michelle Katia
R Castro Botelho Carneiro
Jose
Brito
Paulo Claudia
Lousada Batista
MENEZES, K; NASCIMENTO, MA ; GONÇALVES, JP ; CRUZ, AS; LOPES, DV ; CURZIO, B; BONAMINO, M; DE MENEZES, JL
; BOROJEVIC, R; ROSSI, MID ; COELHO-SAMPAIO, T. Human Mesenchymal Cells from Adipose Tissue Deposit Laminin and
Promote Regeneration of Injured Spinal Cord in Rats. Plos One , v. 9, p. e96020, 2014.
TAKIYA, CM ; BOROJEVIC, R . Cardiac and renal cell therapies: similarities and differences. Kidney International Supplements, v.
1, p. 99-102, 2011.
BLOISE, F. F. ; OLIVEIRA, F. L. ; NOBREGA, A. F. ; VASCONCELLOS, R. ; CORDEIRO, A. ; PAIVA, L. S. ; TAUB, D. D. ; BOROJEVIC R. ;
PAZOS-MOURA, C. C. ; DE MELLO-COELHO, V. . High levels of circulating triiodothyronine induce plasma cell differentiation.
Journal of Endocrinology, 2014
TRIGO, FMB. ; LUIZON,MR. ; DUTRA, HÉLIO S. ; MAIOLINO, Â ; NUCCI, M ; SIMÕES, BP. Interaction between IL-6 and TNF-α
genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).
Leukemia Research Reports, v. 3, p. 76-78, 2014.
BRAND, C. ; OLIVEIRA F. L ; Ricon, L. ; FEMINO, M. L. ; BOLDRINI, L. C. ; Hsu, D. K ; Liu, F.-T. ; CHAMMAS, R. ; BOROJEVIC,
R. ; FARINA, M. ; EL-CHEIKH, MC. . The bone marrow compartment is modified in the absence of Galectin-3. Cell and Tissue
Research (Print)
, v. 346, p. 427-437, 2011.
ANDRADE, LR. ; LINS, U ; FARINA, M ; KACHAR, B ; THALMANN, R. Immunogold TEM of otoconin 90 and otolin relevance to
mineralization of otoconia, and pathogenesis of benign positional vertigo. Hearing Research, v. 292, p. 14-25, 2012.
ROSADO DE CASTRO PH, Pimentel-Coelho PM, Gutfilen B, Lopes de Souza SA, de Freitas GR, Mendez-Otero R, Barbosa da
Fonseca LM3.Radiopharmaceutical Stem Cell Tracking for Neurological Diseases. Biomed Res Int. 2014;2014:417091.
Program overview: research focus
1. BIOMATERIALS FOR TISSUE REPAIR: production and characterization of
biomaterials for application in the repair of various tissues such as skin, nerve, bone
and cartilage;
2. CHARACTERIZATION OF MINERAL PARTICLES: The chemical, biophysical and
morphological characterization of nanoparticles and of crystals obtained upon
experimental biomineralization;
3. CONTROL OF CELL PROLIFERATION AND DIFFERENTIATION: aiming at an efficient
manipulation of stem or progenitor cells for use in cell therapy;
4. IMMUNOMODULATION STUDIES associated to cell therapy and to natural
processes such as aging, degenerative diseases or cancer;
5. THE UNDERSTANDING OF THE ROLE OF TISSUE MICROENVIRONMENTS as a
determinant of cell behavior in several pathophysiological processes.
Program overview: annual activities
Month seminars (at UFRJ, InMetro, CBPF, UFF):
- Thesis presentation
- Intramural and Extramural Researchers
- International Researchers . Visiting Researchers
Annual Workshop
- Presentation of projects under development by Members of the
Bioengineering Researcher program
- To stimulate collaboration and plan organization of meetings and application
to Research grants
Annual discipline at the Graduate Program in Morphological Sciences:
Bioengineering and Tissue Repair (2 weeks- Lectures and scientific papers
presentation) – participation of all Program members and International speakers
In 2015 – will be offered to the undergraduate courses of Biophysics,
Nanotechnology, and Biomedical Sciences - at UFRJ
2014
FERGAL O`BRIEN
RONALDO AMARAL
PhD student
SCIENTIFIC KNOW-HOW
BRAZILIAN GROUP
IRISH GROUP
PLATELET-RICH PLASMA
SCAFFOLDS
CELL BIOLOGY
CARTILAGE TISSUE ENGINEERING
BASIC SCIENCE
APPLIED SCIENCE
Platelet-rich plasma released differently stimulates cellular commitment towards the chondrogenic
lineage according to concentration. Ronaldo JFC do Amaral, Amos Matsiko, Marcel RP Tomazette,
Wanessa KR Rocha, Eric Cordeiro-Spinetti, Tanya J Levingstone, Marcos Farina, Fergal J O’Brien,
Marcia C El-Cheikh, Alex Balduino
SUBMITTED AT JOURNAL OF TISSUE ENGINEERING
2014
AMOS MATSIKO
MARCIA CURY EL-CHEIKH
SCIENTIFIC KNOW-HOW
IRISH GROUP
BRAZILIAN GROUP
SCAFFOLDS
IMMUNOLOGY
3D CELL CULTURE
EPIGENETICS
APPLIED SCIENCE
BASIC SCIENCE
Myeloid differentiation in collagen-hyaluronic acid scaffolds under epigenetic control Mariana
Cabanel, Amos Matsiko, Ronaldo JFC do Amaral, Katia Carneiro, Marcos Farina, Fergal J O’Brien,
Marcia C El-Cheikh
SUBMIITED TO BRAZILIAN AGENCIES FOR FUNDING
Brazil - Ireland Cooperation:
What we can offer
• Brazilian system for ST&I in Health is strong in basic science and
the Government is investing in decreasing the gap between
science and applied technology
• We have plenty of academic freedom (plasticity)
• We have a lot of young people engaged in research
• It is very easy to network
• Competencies in basic science can be identified using different
tools (Pubmed, Lattes, Google, keywords and e-mails
Lattes: http://buscatextual.cnpq.br/buscatextual/busca.do
OBRIGADA!
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