Rohan ShirwaikerAssociate Professor, Industrial & Systems Engineering
Associate Faculty, Biomedical EngineeringDirector, 3D Tissue Manufacturing Research Team
North Carolina State UniversityEmail: [email protected]
Engineered Tissue “Factories”to Enable Bench-to-Bedside Translation
Tissue “Manufacturing”1995
Massachusetts General Hospital (Vacanti et al.)
2016
University of Tokyo and Kyoto University (Takato and Tsumaki et al.)
• Significant progress in relevant fundamentalbiomedical sciences not matched by advances inmanufacturing science to enable scale-up andscale-out.
• Other industries are evolving towards Industry5.0, but engineered tissue technology is stillstriving to make it to 2.0, for the most part.
https://www.smithsonianmag.com/science-nature/history-lab-rat-scientific-triumphs-ethical-quandaries-180971533/
https://www.medicaldaily.com/scientists-use-stem-cells-grow-human-ear-rats-back-371176
Congenital Disorders Trauma & Injuries Chronic Diseases
Pharmaceuticals Surgical Repair Devices & ImplantsGrafts & Transplants
Engineered Tissues: Clinical Needs
Engineered Tissue Technology: Proofs of Concept
Able to grow cells onto biomaterials…..
in patient-specific 3D geometries.….with tissue-specific characteristics…..
https://www.nature.com/articles/nbt.3413 https://iopscience.iop.org/article/10.1088/1758-5090/ab15cf https://science.sciencemag.org/content/364/6439/458
Current State of Tissue “Manufacturing”
Bioinks (Cells + Biomaterials)
Biomodeling(Imaging → CAD/CAM)
Bioprinting Process Modalities
Current State of Tissue “Manufacturing”
Bioinks (Cells + Biomaterials)
Biomodeling(Imaging → CAD/CAM)
Bioprinting Process Modalities
Bioprinting≠
Tissue Manufacturing
Biopsy Processing
Tissue Maturation
Quality Assessment
Packaging &
Shipping
Cell Expansion
Biomaterial Processing
Bioprinting
High-Level Map of Tissue “Manufacturing”
Example: Upstream Challenges
1.E+00
1.E+01
1.E+02
1.E+03
1.E+04
1.E+05
1.E+06
1.E+07
1.E+08
0 10 20 30 40 50 60 70
Num
ber o
f cel
ls (l
og s
cale
)
Time (days)
TARGET
0E+00
2E+04
4E+04
6E+04
8E+04
1E+05
1E+05
1E+05
2E+05
No.
of i
sola
ted
cells
Biopsy#
High upstream variability leads to more significant downstream disruptions (bullwhip effect)⇒ Wasted resources⇒ Scheduling issues in subsequent stages of bioprinting and implantation
For implantationFor quality inspection
Example: Downstream Challenges
Vision for Tissue ManufacturingModular Scalable Smart Factories for
Mass Production of Patient-specific Tissuesat Point-of-Care Pn Biopsy
Pn Data
Pn tissue
• Mass production with lot sizes of one• End-to-end sterile environment with no cross-contamination
between lots• Stochastic processes with high variabilities (pre-dominantly biology
driven)• Process cycle times and production lead times spanning up to
several weeks• Transient properties of living raw material, WIP, and finished product
leading to inventory constraints• 100% inspection• Continuous process improvement challenging due to regulations
Pn Digital Twin
Central QC/QA
Pn Biopsy
• Sterile coverage
• Tissue-neutral
• Self-contained (matl. hand. + data proces.)
• Reconfigurable• AutonomousPn Data
P2tissue
P1tissue
Pn Digital Twin
Vision for Tissue Manufacturing
Cell Seeding
Extrusion Printing
Vision for Tissue Manufacturing
Biopsy Processing
Waste
MincingCell
Isolation
Cell Passaging Pod#2
QC/QA
Cell ExpansionPod#2
Pod#1
BioprintingPod#3
DLP Printing
Tissue Maturation
Pod#4 Incu
batio
n
Incubation
Media/
G. Factors
Media/
G. Factors
Strain Bioreactor
Flow Perfusion Bioreactor
Waste
P2tissuePn Biopsy
P1tissue
Pn Digital Twin
Pn Data
Vision for Tissue Manufacturing
• Taxonomy & Ontology• Cyber-physical System Architecture• Machine Learning & AI• Logistics & Supply Chain Design• Data & Waste Management• Economics & Decision-making Modeling
R&D of Critical Enablers
• Design for X (Tissue Manufacturing, Implantability) • Process Design for Biomimicry• Automation & Robotics• Multi-variate Sensing
• Cells• Biomaterials
Education
Regulations Standards
Collaborations
Acknowledgements
Students, Collaborators & Mentors:
• Dr. Molly Purser• Dr. George Tan• Dr. Pedro Huebner• Dr. Lokesh Narayanan• Parth Chansoria• Karl Schuchard• Priyanka Sheshadri• Claudia Alvarado• Annie Lin• Brent Goldstein
• Dr. Binil Starly• Dr. Paul Cohen• Dr. Richard Wysk• Dr. Ola Harrysson• Dr. Jorge Piedrahita• Dr. Matthew Fisher• Dr. Elizabeth Loboa• Dr. Jeffrey Spang• Dr. Behnam Pourdeyhimi• Dr. Anthony Atala
and others….
Top Related