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BIOACTIVE GLASS-BASED COMPOSITE
SCAFFOLDS FOR TISSUE ENGINEERING
APPLICATIONS
The generation of Prometheus1
1Meyer, U.; et. al. Fundamentals of tissue engineering and regenerative medicine. 2009.
MATERIAL
SCIENCE
CELL
BIOLOGY
LIFE
SCIENCES
CLINICAL
USE
Stimulating tissue to self-regenerate
…“systematically and pharmacologically inert substances designed for
implementation within or incorporation with living system.“
Porosity 50 – 90 %
open and connected
Young‘s modulus 1-2 MPa1
HA:collagen ratio 70:30
Ca:P ratio 1,37 – 1,87
Self-regeneration YES, but limited
Vascularizated tissue Yes, highly
1E. Taheri, B. Sepehri and R. Ganji, "Mechanical Validation of Perfect Tibia 3D Model Using Computed Tomography Scan," Engineering, Vol. 4 No. 12, 2012, pp. 877-880. doi: 10.4236/eng.2012.412111.
2Knauss P. [Material properties and strength behaviour of spongy bone tissue at the coxal human femur. (author's transl)]. Biomed Tech (Berl). 1981 Sep;26(9):200-10. German.
INORGANIC ORGANIC
 Ceramic and glass
 Induce bone mineral formation in vitro
 Highly biocompatible
 Biodegradable
 Low solubility (if highly crystalline)
 Highly brittle // low mechanical strength
 Natural or synthetic biopolymers
 Hydrophilic
 Non-osteogenic
 Low mechanical stiffness
HA
CaP
Bioactive
glass collagen
PEG
Gellan
gum
n/n % SiO2 CaO P2O5 Na2O
BAG-A 70 30
BAG-B 66 22 2 10
3N. Drnovšek and S. Novak, Development of Coatings on Ti6Al4V Alloy for New Generation Implants Bone with Improved Osseointegration: Doctoral Dissertation, N. Drnovšek, 2012.
 Combine bioactive glass particles with natural and synthetic
biopolymer matrix
 Prepare 3D biodegradable scaffolds
 accessible „off-the-shelf“
 applicable with minimum invasivity
 Study the effect of bioactive glass on…
 …scaffolds architecture, mechanical properties, degradation rate
and bioactivity
 Chemical-physical characterization of the composites
Sphingomonas paucimobilis
GG
HS
HS
SH
SH
°
Random coil Double helix HS
HS
SH
SH
Tf GG GG-BAG
- 20 °C
- 80 °C
∼ ∼
∼ ∼
µm
brittle
elastic
softening the dry scaffold by more interactions of scaffold with water
SiO2-CaO SiO2-CaO-P2O5-Na2O
Na+
Na+
PBS
pore size in rehydrated scaffolds
2.42 - 2.52 µm
pH
µm
Ca2+
hydroxyapatite
precipitation
HS
HS
SH
SH
Active participation of BAG in cross-linking? pH
Ca2+ & Si4+
4Tadashi Kokubo, Hiroaki Takadama, How useful is SBF in predicting in vivo bone bioactivity?, Biomaterials, Volume 27, Issue 15, May 2006, Pages 2907-2915, ISSN 0142-9612.
pH
HS
HS
SH
SH
hydroxyapatite
precipitation
Hela
Cell Culture
Insert
Media
Dynamic hydrogel
with or without BAG
nanoparticles
YES Active participation in cross-linking NO (slower dynamic bond exchange)
YES, better with 2-comp. BAG Improved mechanical characteristics YES, hardening effect
More uniform porosity Structure Still able to self-heal
YES, slow Biodegradable with suitable pH profile YES, quite fast
YES Bioactivity of the composite YES
Limited biological evaluation
• Prof. dr. Saša Novak, supervisor
• Jožef Stefan Institute – colleagues at K7 department (dr. Nataša Drnovšek, Rok Kocen,
dr. Martina Lorenzetti, Maja Koblar, Kaja Križman, Mateja Paščinski, Gregor Murn)
• Prof. dr. Janez Stepišnik - Faculty of Mathematics and Physics
• Prof. dr. Odon Planinšek – Faculty for pharmacy
• Slovenian research agency - funding
• COST Action MP1005 NAMABIO „From nano to macro biomaterials (design, processing,
characterization, modeling) and applications to stem cells regenerative orthopedic and
dental medicine“
• 3B‘s research group Minho University (Portugal) – dr. Vitor M. Correlo, prof.dr. Rui L.
Reis, Lucília P. da Silva
• IK4 CIDETEC Biomaterials group – dr. Damien Dupin, dr. Iraida Loinaz, dr. Pablo
Casuso and dr. Adrián Pérez (Spain)

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Gantar_PhD - Copy

  • 1. BIOACTIVE GLASS-BASED COMPOSITE SCAFFOLDS FOR TISSUE ENGINEERING APPLICATIONS
  • 2. The generation of Prometheus1 1Meyer, U.; et. al. Fundamentals of tissue engineering and regenerative medicine. 2009. MATERIAL SCIENCE CELL BIOLOGY LIFE SCIENCES CLINICAL USE Stimulating tissue to self-regenerate
  • 3. …“systematically and pharmacologically inert substances designed for implementation within or incorporation with living system.“ Porosity 50 – 90 % open and connected Young‘s modulus 1-2 MPa1 HA:collagen ratio 70:30 Ca:P ratio 1,37 – 1,87 Self-regeneration YES, but limited Vascularizated tissue Yes, highly 1E. Taheri, B. Sepehri and R. Ganji, "Mechanical Validation of Perfect Tibia 3D Model Using Computed Tomography Scan," Engineering, Vol. 4 No. 12, 2012, pp. 877-880. doi: 10.4236/eng.2012.412111. 2Knauss P. [Material properties and strength behaviour of spongy bone tissue at the coxal human femur. (author's transl)]. Biomed Tech (Berl). 1981 Sep;26(9):200-10. German.
  • 4. INORGANIC ORGANIC  Ceramic and glass  Induce bone mineral formation in vitro  Highly biocompatible  Biodegradable  Low solubility (if highly crystalline)  Highly brittle // low mechanical strength  Natural or synthetic biopolymers  Hydrophilic  Non-osteogenic  Low mechanical stiffness HA CaP Bioactive glass collagen PEG Gellan gum
  • 5. n/n % SiO2 CaO P2O5 Na2O BAG-A 70 30 BAG-B 66 22 2 10 3N. Drnovšek and S. Novak, Development of Coatings on Ti6Al4V Alloy for New Generation Implants Bone with Improved Osseointegration: Doctoral Dissertation, N. Drnovšek, 2012.
  • 6.  Combine bioactive glass particles with natural and synthetic biopolymer matrix  Prepare 3D biodegradable scaffolds  accessible „off-the-shelf“  applicable with minimum invasivity  Study the effect of bioactive glass on…  …scaffolds architecture, mechanical properties, degradation rate and bioactivity  Chemical-physical characterization of the composites
  • 9. ° Random coil Double helix HS HS SH SH
  • 10.
  • 11. Tf GG GG-BAG - 20 °C - 80 °C ∼ ∼ ∼ ∼ µm
  • 12. brittle elastic softening the dry scaffold by more interactions of scaffold with water
  • 14. PBS pore size in rehydrated scaffolds 2.42 - 2.52 µm pH µm Ca2+
  • 17.
  • 18. Active participation of BAG in cross-linking? pH
  • 19.
  • 20.
  • 21. Ca2+ & Si4+ 4Tadashi Kokubo, Hiroaki Takadama, How useful is SBF in predicting in vivo bone bioactivity?, Biomaterials, Volume 27, Issue 15, May 2006, Pages 2907-2915, ISSN 0142-9612. pH HS HS SH SH hydroxyapatite precipitation
  • 23. YES Active participation in cross-linking NO (slower dynamic bond exchange) YES, better with 2-comp. BAG Improved mechanical characteristics YES, hardening effect More uniform porosity Structure Still able to self-heal YES, slow Biodegradable with suitable pH profile YES, quite fast YES Bioactivity of the composite YES Limited biological evaluation
  • 24. • Prof. dr. Saša Novak, supervisor • Jožef Stefan Institute – colleagues at K7 department (dr. Nataša Drnovšek, Rok Kocen, dr. Martina Lorenzetti, Maja Koblar, Kaja Križman, Mateja Paščinski, Gregor Murn) • Prof. dr. Janez Stepišnik - Faculty of Mathematics and Physics • Prof. dr. Odon Planinšek – Faculty for pharmacy • Slovenian research agency - funding • COST Action MP1005 NAMABIO „From nano to macro biomaterials (design, processing, characterization, modeling) and applications to stem cells regenerative orthopedic and dental medicine“ • 3B‘s research group Minho University (Portugal) – dr. Vitor M. Correlo, prof.dr. Rui L. Reis, Lucília P. da Silva • IK4 CIDETEC Biomaterials group – dr. Damien Dupin, dr. Iraida Loinaz, dr. Pablo Casuso and dr. Adrián Pérez (Spain)