Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of...
Transcript of Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of...
![Page 1: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/1.jpg)
1
Frank P. Luyten, MD, PhD
Division of Rheumatology, UZ Leuven
Skeletal Biology & Engineering Research Center
Prometheus, KU Leuven, 2015
Engineering for Health: ICT & Nanotechnology
![Page 2: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/2.jpg)
2
CASE: 45 YEAR-OLD PATIENTPRESENTS WITH ARTHRITIS
New Technologies in Patient Care
![Page 3: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/3.jpg)
3
Diagnostic work out…
• Anamnesis: inflammatory
• Clinical examination: synovitis/swelling right knee, discrete swelling both wrists
![Page 4: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/4.jpg)
4
INFECTIOUSINFLAMMATORY (RA, SPA..) CRYSTALARTHROPATHY (GOUT, CPPD)
DD
![Page 5: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/5.jpg)
5
INFECTIOUS ?
• Puncture knee: 20 cc liquid…
– analysis: cell count, cell type, glucose,
– Analysis: microscope: Gram staining, crystals ?
– Cultures…
• Point of need/care ? Minilabs….see JVH
![Page 6: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/6.jpg)
6
DD INFLAMMATORY ARTHRITIS
SF: 12.000 cells, no crystals, no bugs, glucose normal
![Page 7: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/7.jpg)
7
Subacute oligo-arthritis
• DD
– Spondylarthropathy: Psoriatic arthritis, reactive arthritis, IBD associated arthritis
– Rheumatoid arthritis
• Labo: Not really urgent, but reliable: RF, anti CCP
antibodies, CRP, ESR…
• (X-rays)
• Patient files ? – Frequently limited, get access to files over internet
– Access to Xrays and original images: Pacsonweb
![Page 8: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/8.jpg)
8
CHRONIC ARTHRITIS: IDENTIFICATION OF PATIENT AT RISKRESPONSE TO TREATMENT
RF +, Anti CCP +: most probable diagnosis “Early RA”
![Page 9: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/9.jpg)
9
Treatment & Management
• Treatment: precision medicine
– Disease activity: clinical & biochemical parameters
– Prognostic biomarkers
– Genetic profile
• Conclusion: high risk profile, induction/remission….
![Page 10: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/10.jpg)
10
Tight disease management
• Response to treatment: preventing joint damage, stop non efficacious expensive treatments: clinical, biochemical, biomarkers…
• Toxicology: follow up of liver tests, kidney function…
![Page 11: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/11.jpg)
11
Follow up Function
• Activities of Daily Live (ADL), recreational & professional activities
– Subjective: Patient questionaires online
– Objective measures in specific cases (old…): mobility sensors, remote sensing
![Page 12: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/12.jpg)
12
Sensor-based Platform for the Accurate and Remote monitoring of Kine(ma)tics Linked to E-health
(SPARKLE)
IDO KULeuven funded project, 2014-2018
General aims
o Improve assessment of movement-
related functioning in
musculoskeletal diseases and beyondo joint mobility, movement-evoked
pain, motor control, activity capacity
and activity performance, physical
activity
o Innovate patient-centered
management in these diseases
o Develop a human model to study
interactions between disease
processes and mechanical tissue
loading
Consortium: UZLEUVEN, ESAT-MICAS,
ESAT-STADIUS, GROUP-T, FABER,
BIOMECH
![Page 13: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/13.jpg)
13
Smart
algorithms
Novel outcome
measures
Sensor node
Access point
RF
Personal computer
Tablet
Smartphone
Data
logger
and
storage
Wireless Body Area
Network (WBAN)Motion/EMG
Feedback
Patient
Care provider
T. Swinnen
Sensor-based platform for the remote monitoring of kine(ma)tics linked to e-health (SPARKLE)
![Page 14: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/14.jpg)
14
REGENERATIVE MEDICINE
Some years later: 50 year old, heavilydamaged knee….???
![Page 15: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/15.jpg)
15
15
Disease control
Adapt lifestyle
NSAIDS
DMARDS
Biologicals
Regenerative solutions to bridge the gapS
eve
rity
of sym
pto
ms
Time: duration of symptoms
Regeneration Replacement
Joint replacement
Joint revision
GAP
![Page 16: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/16.jpg)
16
The New Frontier: A Biological Joint
Lopa & Madry, TE 2014
![Page 17: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/17.jpg)
17
Extrinsic Repair
• Stem cells: progenitors, embryonic, iPS(induced pluripotent stem cells)
• Combination products: stem cells, growthfactors, smart scaffolds
• Engineered Bioartificial Tissues
![Page 18: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/18.jpg)
18
FROM BENCH TO BEDSIDE
Path of Development
![Page 19: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/19.jpg)
19
Animal models
• Ectopic nude mouse/rat model• Standard in vivo potency assay
• Orthotopic (nude) mouse/rat model• Critical tibial load-bearing defect (5mm)• Integration with host bone
• Orthotopic, load-bearing rabbit model• Large tibial bone defect (2 cm)• 2 types of external fixators• Clinical size, training & process
robustness
• Orthotopic, load-bearing sheep tibial critical size defect & non union model
• Defects of 3-5 cm, young and adult• ‘Patient’ – fit standard of care
![Page 20: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/20.jpg)
20
MANUFACTURING CHALLENGES REQUIRINGTECHNOLOGY DEVELOPMENTS
New Frontier: 3D living implant
![Page 21: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/21.jpg)
21
Fundamental
research
Applied research
(TE)
Industry
Socio-economical reality
University
Market
Focus on application, brigde ‘gap’ Large ‘gap’
Organised valorisation strategy Ad hoc valorisation
Added value KULeuven know-how No focus
Increase succes rate No critical mass
?
PROMETHEUS
Clinical problem
Pre-clinical model
to bridge the gap
Translational Research
![Page 22: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/22.jpg)
22
Enabling technologies
• Microfluidics
• Bioreactors
• Biosensors
• Non invasive imaging
• 3D Bioprinting
• Computational modeling
![Page 23: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/23.jpg)
23
From laboratory to industrial scale expansion
1.8
m
120 flasks T-175 yield 400
million cells. Traditional 2D cell
culture requires routine manual
interventions daily.
A hollow fiber bioreactor, provides a cell
culture surface area, which is equivalent to the
surface area of 120 T-175 flasks. Bioreactor
culture requires a single manual intervention.
“Miniaturization”
![Page 24: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/24.jpg)
24
From 2D to 3D: Bioreactor design evolution
Bioprocess monitoring and control
1st Generation 2nd Generation 3rd Generation
Incubator Incubator Benchtop incubator
![Page 25: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/25.jpg)
25
66 micron 150 micron
Fabrication of 3D microaggregation platform
3-11-2015
![Page 26: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/26.jpg)
26
Mass transport: Oxygen biosensor
3 november 2015 All rights reserved © 2012, KULeuven 26
• Oxygen sensing nanobeads
– Online
– Non-interfering
– Spatial resolution
– Versatile
Alexa Fluor 488 Ruthenium complex
Nile Blue Overlay
1 2
31 2
3
![Page 27: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/27.jpg)
27
Perfusion bioreactor-spatial optimization
*Papantoniou et al. Biotechnol & Bioeng., 2014.
![Page 28: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/28.jpg)
28
Neo-tissue growth modeling
Culture time
• Study interdependence between neo-tissue growth kinetics
and local environment
• Link to process-scale conditions
• Optimize culture protocols
![Page 29: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/29.jpg)
29
NanoCT
QUANTITATIVE:3D image analysis
QUALITATIVE:Virtual 2D histology
+ and / or
Neo-tissue formation in cultured TE constructs
Contrast agents
Hexabrix®
Photo-tungstic acid (PTA)
03/11/2015 29
Contrast-enhanced nanoCT
![Page 30: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/30.jpg)
30
3 november 2015 All rights reserved © 2013, KULeuven 30
Large animal studies: feasibility
![Page 31: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/31.jpg)
31www.kuleuven.be/prometheus
PrometheusDivision of Skeletal Tissue Engineering
![Page 32: Engineering for Health - KU Leuven...2015/11/03 · 1 Frank P. Luyten, MD, PhD Division of Rheumatology, UZ Leuven Skeletal Biology & Engineering Research Center Prometheus, KU Leuven,](https://reader036.fdocuments.us/reader036/viewer/2022071110/5fe4d7efac13ef78bd05516f/html5/thumbnails/32.jpg)
32
Acknowledgements
• Skeletal Biology and Engineering Research Center: www.uzleuven.be/rheumatology
• Prometheus:interdisciplinary platform www.kul.be/prometheus
• Stem Cell Institute Leuven (SCIL-Verfaillie): www.kul.be/scil