TR&D-4: Growing Tissue in the Scalable, Modular, Automated, and Closed (SMAC) Foundry

Project Summary/Abstract:
TR&D-4 will demonstrate process automation on ARMI|BioFabUSA’s Tissue Foundry, a scalable, modular,
automated and closed tissue manufacturing platform. The Tissue Foundry is the integration of primarily off-the-
shelf components to perform the sequential, modular steps of producing a tissue. The Tissue Foundry automates
thawing a vial of adherent cells, expanding them on microcarriers in stirred tank vessels, harvesting cells and
exchanging cells into media promoting subsequent differentiation or tissue development steps, culturing the
tissues during maturation, and preservation and packaging of the final product. To re-design the manual process
to the closed, automated Tissue Foundry process, ARMI’s Deep Tissue Characterization Center deconstructs a
manual process and develops tissue-type specific setpoints at both the endpoint and at intermediate stages of
production using experimentation and modeling after deep multiparameter characterization of the cells and
tissue. Once these setpoints are identified significant gaps remain in available tissue specific sensors and
equipment to control and monitor tissue quality.
Advanced sensor technologies (developed in TR&D-1 and –2) and prototype, actuator-enabled
bioreactors (TR&D-3) will be integrated into the Tissue Foundry and demonstrated through production
of CP target tissues in a tissue manufacturing relevant environment. This objective will be carried out in 3
specific aims: Aim 1: Physical integration of sensors with Tissue Foundry cell culture system. We will
integrate newly-developed biosensors developed in TR&D-1, -2, and -3 into the Tissue Foundry for both
measurement of parameters specific to the tissue process, and as a proof of concept for the feasibility of
controlling these processes through feedback loops. Aim 2: Efficient control by integration of sensors and
actuators with Tissue Foundry backbone automation and data management system. Tissue Foundry
control is based on a supervisory control and data acquisition (SCADA) architecture and on the use of
programmable logic controllers (PLCs), which will interface directly with sensors and actuators executing
processing steps and real-time feedback control. Aim 3: Automated production of up to 10 tissues
simultaneously. A manual tissue engineering process, starting with CCMEEC’s articular cartilage, will be
assessed to identify optimal automation and sensor implementation. Once configured, the Tissue Foundry will
be used to produce up to 10 tissues simultaneously using integrated bio-instructive bioreactors. Data from each
step and the final product will be collected through integrated sensors, analysis of media aliquots, and destructive
sampling to compare the manual and automated processes. TR&D4 will deliver an automated manufacturing
system, leveraging the existing modules of the prototype Tissue Foundry, with vastly improved
capabilities developed by TR&D-1, -2, and -3, for reliably producing complex tissues

Grant Number: 5P41EB021911-09
NIH Institute/Center: NIH
Principal Investigator: Thomas Bollenbach