Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano...
Transcript of Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano...
![Page 1: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/1.jpg)
Rapid prototyped nano composite
magnetic scaffolds for osteochondral
tissue regeneration
Roberto De Santis
IPCB-CNR Institute of Polymers, Composites and Biomaterials,
National Research Council of Italy
V.le J.F. Kennedy, 54 Naples 80141, Italy
![Page 2: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/2.jpg)
Additive Manufacturing
- opportunities in Tissue Repair & Regeneration
Nano-composite magnetic scaffolds
- Iron Oxide & Iron doped Hydroxyapatite (MNPs)
- PCL/MNPs PEG/MNPs nanocomposites
- Properties of superparamagnetic scaffolds
Features of superparamagnetic scaffolds used in conjunction with
magnetically labeled cells
RP of nanocomposite scaffolds for osteochondral tissue regeneration
Outlines
![Page 3: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/3.jpg)
Ink-jet
FDM
STL
Spraybase
Indirect Application
of AM (molding)
Additive Manufacturing opportunities in the
MedTech industry (non-implantable devices)
Direct Application of
AM
![Page 4: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/4.jpg)
MSC-loaded collagen-LMW HA-4S-StarPEG sIPN
Combination of 3D Photo-Printing and 3D Fiber Deposition
techniques
Combination of 3D Fiber DepositionTechnique and Electrospinning
cm mm
µm nm3D Bioplotting in conjunction with
solvent casting/phase inversion
Additive Manufacturing opportunities in the
MedTech industry (implantable devices)
![Page 5: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/5.jpg)
Rationale for manufacturing magnetic scaffolds
on demand
drug delivery
smart cell
seeding
![Page 6: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/6.jpg)
Iron Oxide & Iron Doped Hydroxyapatite MNPs
Fe3O4@PAA
FeHA
Superparamagnetic nanoparticles
![Page 7: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/7.jpg)
PCL/MNPs
90/10 to 50/50 w/w
Poly(ethylene glycol) diacrylate (PEGDA)
Lucirin-TPO photoinitiator
Stirring & SonicationPCL/MNPs & PEG/MNPs
solutions
Moulding & Solvent CastingTeflon Mould
2D nanocompositespellets
Poly(ε-caprolactone) (PCL)
3D Fiber Deposition
Stereolithography
PCL/MNPs & PEG/MNPs nanocomposites
![Page 8: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/8.jpg)
PCL/MNPs nanocomposites
P Ca Fe
PCL/FeHa 80/20
![Page 9: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/9.jpg)
fiber
3D scaffold
Optical Microscopy
a) b) c)
µ-CTFe3O4
filtering
PCL/MNPs imaging
![Page 10: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/10.jpg)
Small-Punch Test (ASTM 2183)
Effects of MNPs amount
![Page 11: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/11.jpg)
-1.0 -0.5 0.0 0.5 1.0
-1
0
1 90/10
80/20
70/30
60/40
50/50
em
u.g
-1
H (T)
PCL/FeHA
T=300K
0 100 2000
3
6
9
90/10
80/20
70/30
60/40
50/50
T
(C
)
t (s)
PLC /FeHA %(w/w)
10 20 30 40 500,0
0,1
0,2
0,3
dT
/dt
(C/s
)
%FeHA (PLC+FeHA)
Effects of MNPs amount
Static Magnetic Field
Dynamic Magnetic Field
![Page 12: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/12.jpg)
-1,0 -0,5 0,0 0,5 1,0-1,5
-1,0
-0,5
0,0
0,5
1,0
1,5
10 layers
LP_A
LP_B
SP_A
SP_B
D=4A
D=4B
PCL/Fe3O
4
80 / 20
M (
em
u/g
)
H (T)
0 60 1200
10
20
T
(°C
)
t (s)
PCL-Fe3O
4 80/20
small pores 10 layers; m=70 (mg)
large pores; m=57,3 (mg)
small pores; m=47,2 (mg)
2 specimens; m=41,9 (mg)
Core Shell MNPPAA@MNP
BSDfunctionalisation
BSDMolecular Collapsing
42 oC
BoundVEGF
ReleasedVEGF
Thermoresponsive dendrimers
Magnetic force
On demand drug delivery opportunities
Static Magnetic Field Dynamic Magnetic Field
![Page 13: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/13.jpg)
PCL/MNPs customized scaffolds for cell assay
![Page 14: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/14.jpg)
(A I) (A II) (A III)
(B I) (B II) (B III)
(C I) (C II) (C III)
(D I) (D II) (D III)
PCL
PCL/MNPs
90/10
PCL/MNPs
80/20
PCL/MNPs
70/30
7 days 14 days 21 days
% R
ed
uc
tio
n A
lam
ar
Blu
eA
LP
Ac
tivit
y (
ng
AL
P/n
g D
NA
)
Time (days)
hMSCs
Gloria A, et al. J R Soc Interf 2013;10: 20120833.
PCL/MNPs nanocomposites: in vitro assay
![Page 15: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/15.jpg)
Materials Contact Angle, θ (deg)
PCL 81.4 ± 4.4
PCL/MNPs 90/10 75.7 ± 4.6
PCL/MNPs 80/20 74.8 ± 2.6
PCL/MNPs 70/30 64.9 ± 8.2
TEM
Imaging
Contact
Angle
MNPs provide a nanostructured topography &
increase PCL hydrophilicity
Russo T, et al. Procedia Eng 2013
PCL/MNPs nanocomposites: contact angle
![Page 16: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/16.jpg)
De Santis R, et al. J. of Biomedical Nanotechnology 2015;11:1236-1246
Cell growth was 2.2-fold greater than that
without the application of a magnetic field.
hMSC loading was 36% higher than seeding
without a magnetic field.
MF
magnetic labeled hMSC
Effect of a static magnetic field
![Page 17: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/17.jpg)
HUVEChMSC
Effect of a static magnetic field
V. Goronov et al, submitted to Journal of Tissue Engineering 2017
![Page 18: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/18.jpg)
Sinusoidal magnetic field
f =70Hz
A=25-30 mT
Stimulation cycle
18 min. + 54 min. relax
Daily stimulation
6 h/day
hMSC
T Russo et al, Bioactive Materials 2017
Effect of a dynamic magnetic field
![Page 19: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/19.jpg)
Hystological investigation at 4 weeks post-
implantation showed mineralized tissue
regeneration around and into the scaffold
In vivo behaviour of magnetic scaffolds
implanted into rabbit femur
PCL/MNPs scaffolds: in vivo behaviour
De Santis R, et al. J. of Biomedical Nanotechnology 2015;11:1236-1246
![Page 20: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/20.jpg)
Stereolithography
Advantage: stratification thickness
Drawback: amount of inorganic particles
FDM
Advantage: amount of inorganic particles
Drawback: stratification thickness
Osteochondral
tissue
Rational for combining FDM & Stereolithography
Scaffolds for osteochondral tissue regeneration
![Page 21: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/21.jpg)
Tissue Engineering
Scaffolds for osteochondral tissue regeneration
![Page 22: Rapid prototyped nano composite magnetic scaffolds for … · 2019-11-25 · Rapid prototyped nano composite magnetic scaffolds for osteochondral tissue regeneration Roberto De Santis](https://reader034.fdocuments.us/reader034/viewer/2022050517/5fa11075b254fc40a037ffc9/html5/thumbnails/22.jpg)
Thank you for the attention
Acknowledgements
POR Timing
Nanomax N-CHEM Progetto Bandiera
MAGISTER FP7 NMP3-LA-2008-214685
V.Alek Dediu
Anna Tampieri
Jose Rivas
Maurilio Marcacci
Vitaly Goranov
Alessandro Russo