Engenharia de Tecidos Humanos: Um breve Resumo do Estado da Arte e Algumas Evoluções Recentes
João F. Mano
3B´s Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer 3B´s Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, Campus de Gualtar, 4710-057 Braga, PortugalEngineering, Campus de Gualtar, 4710-057 Braga, Portugal
IBB- Institute for Biotechnology and Bioengineering, Braga, PortugalIBB- Institute for Biotechnology and Bioengineering, Braga, Portugal
PhD Students/ Other Full time ResearchersAdriano PedroAlbino MartinsAna MendesAna PinheiroAna OliveiraAna SousaAna PintoAnabela PintoBarbara BertiniBrecht ClaesBruno FerreiraCatarina AlvesCornelia BrunnerDaniela CoutinhoElisabete PinhoElizabeth BalmayorEmanuel FernandesHelena LimaIsabel LeonorIvo ArosoJessica GrechJoana MagalhãesJoão OliveiraJoaquim FerreiraJoaquim OliveiraJosé Rodriguez
3B´s RESEARCH GROUP
Staff - Rui L. Reis (Director)- João F. Mano- Nuno M. Neves- Natália Alves
José PereiraJosé JúniorKadriye TuzlakogluLeandro GardelMárcia RodriguesMarina SantosMarta SilvaPatrícia BaptistaPaula SolPaula PérezPaulo BessaRicardo SilvaRogério SousaRosa BessadaSandra OsórioSangwong ChungSatyabrata GoshSílvia PereiraSimone SilvaSusana SantosTeresa SilvaTírcia SantosTommaso RadaVitor Espírito SantoVítor SilvaWojciech Szymczyk
Technical StaffAriana SantosBárbara BarrosoBerta AlmeidaFilipe RibeiroLiliana GomesRicardo GomesTânia Delalande AlvesVirgínia Araújo
Other PhD HoldersAlexandra MarquesAna GrenhaAna FriasAntónio SalgadoCarlos ViegasErkan BaranGabriela SilvaHelena AzevedoIsabel DiasIva PashkulevaJohan BeneschLuciano BoeselMaria Manuela GomesMazen TamerRicardo PiresRita SerraRui Amandi de SousaSandra SampaioSusana MartinsTiago SilvaZhongkui Hong
“Tissue Engineering (TE) is an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function”
Langer and Vacanti., Science 260, 920 (1993)
TE: AN INTERDISCIPLINARY SCIENCE
Medical science
BiologyBiochemistry
Materials Science& engineeringChemistry TE
cells
+ Growth factors
CONSTRUCTION OF HUMAN TISSUE SUBSTITUTES
What material??•Biodegradable
polymers
Which structure ??
•Porous/interconected
Which processing method??
SCAFFOLD
Materials used at the 3B’s Group
Starch + EVOH or CA or PCL or PLA High potential for a all range of biomedical applications: - tissue engineering scaffolding - drug delivery carrier systems - bone replacement / bone defects; bone plates / screws; partially degradable bone cements
O
CH2OH
H
H
H
OH
NHCOCH3
HH
O
O
CH2OH
H
H
H
OH
NHCOCH3
HH
O
n
GlcNAc
O
CH2OH
H
H
H
OH
NH2
HH
O
O
CH2OH
H
H
H
OH
NH2
HH
O
n
CHITIN
Deacetylation
CHITOSAN
GlcNAc
+ CH3COONa
NaOH, temperature
Chitosan based materials
other polysaccharides, proteins and blends with biodegradable polyesters…
3B´s SCAFFOLD PROCESSING ROUTES3B´s SCAFFOLD PROCESSING ROUTES
Injection moulding with blowing agents Injection moulding with blowing agents
Extrusion with blowing agentsExtrusion with blowing agents
Microwave BakingMicrowave Baking
Fiber Bonding (Wet or Melt-spinning)Fiber Bonding (Wet or Melt-spinning)
Compression moulding and salt leachingCompression moulding and salt leaching
Solvent casting-particle leachingSolvent casting-particle leaching
In-situ polymerizationIn-situ polymerization
(In-situ) Enzymatic Degradation(In-situ) Enzymatic Degradation
Freeze dryingFreeze drying
Rapid prototypingRapid prototyping
………………
ceramic+chitosan bilayered scaffolds
polyurethane sponge
HA slurry
burningchitosan solution
freeze-drying
pore size: 50 – 350 µm
STEM /PROGENITOR CELLS• EMBRYONIC
• BONE MARROW
• ADIPOSE TISSUE
• UMBILICAL CORD
• AMNIOTIC MEMBRANE
Cell response to bilayered scaffoldsCell response to bilayered scaffolds
100 µm
20 m
cartilage region
bone region
condrogenic medium
osteogenic medium
goat marrow cellsgoat marrow cells
28 days
14 days
Isabel Dias, Carlos Viegas
Human Osteoblast-like cells (SaOs-2) and human fibroblasts
(MRC-5)
Cell encapsulation and co-cultures
Osteoblasts
Fibroblasts
CaCl2+NaCl
sodium alginate + Iota carrageenan
+ cells
+
---
-
-
---
-
-
++
+ ++
+
+
++
+
+
+
+
+
Polyanion
Ca2+ ions
Cells
SaOs-2 with CMC/PAMAM-FITC INTERNALIZATION OF INTERNALIZATION OF CMC/PAMAM-FITC NANOPARTICLESCMC/PAMAM-FITC NANOPARTICLES
after 14 days
PAMAMPAMAMdendrimersdendrimers CarboxymethylCarboxymethyl--chitosanchitosan
++
CMCCMC//PAMAMPAMAM
DendronizedDendronized polymerpolymer
PAMAMPAMAMdendrimersdendrimers CarboxymethylCarboxymethyl--chitosanchitosan
++
CMCCMC//PAMAMPAMAM
DendronizedDendronized polymerpolymer
novelnovel carboxymethyl-chitosan/poly carboxymethyl-chitosan/poly (amidoamine)(amidoamine) (CMC/PAMAM) (CMC/PAMAM) dendronized polymersdendronized polymers (natural-based (natural-based polymers + dendrimers).polymers + dendrimers).
EU FUNDED PROJECTSEU FUNDED PROJECTS
STREP – HIPPOCRATES
Marie Curie EST - ALEA JACTA EST
NoE – EXPERTISSUES
Marie Curie SCF - InVENTS
• STREP – WaCheUp• IP-GENOSTEM• NANOPHOTOTECH• Marie Curie EST JoinTEd• Marie Curie: POLYSTEM
PROTEUSINTERREG IIIA
NEW JOURNAL - TERM
Editor-in-ChiefProf. Rui L. Reis
BiomaterialsBiomaterialsBiodegradablesBiodegradables
BiomimeticsBiomimetics
www.3bs.uminho.pt