Publication of presentation by Mani Diba MSc of Radboudumc, The Netherlands on Nanoparticles as building blocks for development of self-healing materials for regenerative medicine. Innoboot 2017, Nijmegen, The Netherlands on April 11, 2017.

1. Nanoparticles as Building Blocks for
Development of Self-Healing Materials
for Regenerative Medicine.
Mani Diba
Department of Biomaterials
Radboud University Medical Center
11th April 2017

2. 2
Regenerative Medicine
Regenerative medicine is a multidisciplinary field which
aims to repair or replace lost or damaged body parts.
Three main components:
• Biomaterials
• Cells
• Biomolecules

3. 3
Ideal Biomaterial for Regenerative Medicine
But how to apply this “ideal” biomaterial???

4. How to apply a biomaterial?
4
Problem:
When a material is extruded/injected, it experiences extensive shear forces
Yielding and loss of mechanical integrity
Solution:
Self-healing biomaterials
 Injection is the essential/preferred method in various applications including:
3D Printing
Minimally Invasive Treatments

5. Self-Healing Materials
5
 Materials that can heal themselves after damage
How can we make
a self-healing biomaterial?

6. Biomaterials for Regenerative Medicine
6
Strategies:
Advantages of Bottom-up
Precise control over building blocks
Substantial control over bulk properties
Building blocks as carrier for multiple
drugs and/or growth factors
Special properties, e.g. self-healing

7. Water
Our Approach
to self-healing biomaterials
(A bottom-up strategy)
7
 Nanoparticles as building blocks
of colloidal (particle-based) gels:
• Organic
(e.g. gelatin)
• Inorganic
(e.g. bioactive glasses and ceramics)
• Functionalization or loading with
biomolecules/drugs

8. Self-healing in colloidal gels
8
Reversible self-assembly of nanoparticles
Reversible bonds
__
+

9. Why nanoparticles?
91Wang et al., Biomaterials, 33, 2012, 8695-8703.
Micro vs. Nano
Size matters!

10. Aim
 To develop composite hydrogels with high elasticity and self-healing
10
Average Diameter ≈ 400nm (swollen) Average Diameter ≈ 80nm
M. Diba, et al., Advanced Materials 2017, 1604672.

11. 11
Controlling interactions between the nanoparticles:
GelatinSilica
Repulsion
Initial
condition
_
Attraction
_
+
Final
condition

12. 12
Gel formation process
Confocalfluorescent
microscopy
pHmeasurement
Rheology
measurement
G'
G"
250x
Gel
formation

13. 13
InjectableMoldable
HighlyElastic

14. 14
R = Silica/gelatin particles mixing ratio
φ = Particle volume fraction
Self-healing after injection

15. 15
Tensile testCompression test

16. 16
In vivo evaluation in osteoporotic rats
1 mm 1 mm 1 mm
Empty defect Filled with gel
Filled with gel+
Anti-osteoporotic drug
12 weeks 8 weeks 8 weeks
(1) (2) (3) (4)
Femoral condyle defects

17. Conclusions
17
Nanoparticles are versatile building blocks for
development of multifunctional biomaterials.
Such biomaterials can be designed to:
• Self-heal after mechanical damage
• Stimulate bone regeneration
• Locally deliver therapeutic drugs

18. Next steps….
18
 Development of gels with more bioceramic content and higher
bioactivity
 Large-scale production of the nanoparticles and gels through
cooperation with:
• Rousselot (world's leading producer of gelatin)
• CAM Bioceramics (producer of bioceramic particles)
• Smartodont (producer of bio-glass particles)
We are open for collaboration
with new business partners

19. Acknowledgments
19
Dr. Sander Leeuwenburgh
Prof. John Jansen
Dr. Jeroen van den Beucken
Winston Camargo, DDS
Prof. David Weitz
Prof. Huanan Wang
Dr. Tom Kodger
Dr. Shima Parsa
IOP Self-Healing Materials
Funding:

20. Thanks for your attention
Email : Mani.Diba@Radboudumc.nl