Bioreactor for 3D Bio-printed Vessels

*Please note the ISC Website will be available on May 24, 2023 at 10:30 EDT

**AMENDMENT 003 - An attachment has been added to extend the closing date for this challenge to July 19, 2023 at 14:00 EDT.

**AMENDMENT 002 - An attachment has been added. The document contains questions and answers related to the Challenge.

This Challenge Notice is issued under the Innovative Solutions Canada Program (ISC) Call for Proposals 003 (EN578-20ISC3). For general ISC information, Bidders can visit the ISC website: http://www.ic.gc.ca/eic/site/101.nsf/eng/home

Please refer to the Solicitation Documents (https://canadabuys.canada.ca/en/tender-opportunities/tender-notice/pw-20-00899125) which contain the process for submitting a proposal. Steps to apply: Step 1: read this challenge Step 2: read the Call for Proposals : https://canadabuys.canada.ca/en/tender-opportunities/tender-notice/pw-20-00899125 Step 3: propose your solution here : https://ised-isde.canada.ca/site/innovative-solutions-canada/en/bioreactor-3d-bioprinted-vessels

Challenge title: Bioreactor for 3D Bioprinted Vessels Challenge sponsor: National Research Council (NRC)

Funding Mechanism: Contract MAXIMUM CONTRACT VALUE: Multiple contracts could result from this Challenge.

Phase 1: • The maximum funding available for any Phase 1 contract resulting from this Challenge is : $150,000.00 CAD excluding applicable taxes, shipping, travel and living expenses, as required. • The maximum duration for any Phase 1 contract resulting from this Challenge is up to 6 months (excluding submission of the final report). • Estimated number of Phase 1 contracts: 2

Phase 2: Note: Only eligible businesses that have successfully completed Phase 1 will be invited to submit a proposal for Phase 2.

• The maximum funding available for any Phase 2 contract resulting from this Challenge is : $1,000,000.00 CAD excluding applicable taxes, shipping, travel and living expenses, as required. • The maximum duration for any Phase 2 contract resulting from this Challenge is up to 24 months (excluding submission of the final report). • Estimated number of Phase 2 contracts: 1

This disclosure is made in good faith and does not commit Canada to award any contract for the total approximate funding. Final decisions on the number of Phase 1 and Phase 2 awards will be made by Canada on the basis of factors such as evaluation results, departmental priorities and availability of funds. Canada reserves the right to make partial awards and to negotiate project scope changes.

Note: Selected companies are eligible to receive one contract per phase per challenge.

Travel No travel is anticipated in Phase 1. Project meetings will be conducted via video conferencing. Kick-off meeting Kick-off meeting will be conducted via video conferencing. Progress review meeting(s) Any progress review meetings will be conducted by videoconference. Final review meeting Final meeting will be conducted via video conferencing. Challenge Statement Summary The National Research Council of Canada (NRC) is seeking an aseptic bioreactor chamber that provides a controlled environment with a perfusion-enabling system to achieve optimal growth of 3D bioprinted hollow tube (blood vessel-like) structures while providing biomechanical stimuli (perfusion shear stress) that mimics vascular hemodynamic forces.

Challenge Problem statement

3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineered constructs. Given its scalability, reproducibility, and precise multi-dimensional control, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. To address this challenge, the NRC is 3D bioprinting hollow tube blood vessels using a microfluidic based platform and alginate-based hydrogel bioinks coupled with endothelial and stromal cells. Enabling cell growth and full maturation of the 3D bioprinted vascular tissues requires a custom perfusion-capable bioreactor platform that can recapitulate vascular biomechanical and biochemical stimuli to support long term blood vessel growth and maturation. Bioreactors can aid the production of functional 3D tissues by maintaining and supporting a desired hollow tube architecture, controlling environmental parameters (e.g., temperature, pH, pressure, oxygen tension, metabolites, regulatory molecules, and shear stress) and metabolic parameters (e.g., nutrient provision, waste removal, and sampling), while allowing for therapeutic perfusion/administration and sampling capabilities. The successful establishment of such a bioreactor system will accelerate the development of 3D tissue models to serve as a pre-clinical platform to advance therapeutic research and development. Desired outcomes and considerations

Essential (mandatory) outcomes

The proposed solution must: 1. Be fabricated with biocompatible materials that can sustain long term cell culture media exposure (3 months +) without cytotoxicity. 2. Fit into a conventional cell culture incubator or be a standalone cell culture bioreactor. 3. Allow for incorporation of 3D bioprinted ultrasoft (1 – 10 kPa) hydrogel hollow tubes into the bioreactor. 4. Have the ability to secure both ends of the hydrogel tube so that it is kept in place and remains leakage-free for up to 60 days. 5. Accommodate incorporation of hydrogel tube length: 1 – 5 cm 6. Accommodate incorporation of hydrogel outer diameter range: 300 µm to 2000 µm & accommodate incorporation of hydrogel inner diameter range: 200 µm to 1200 µm. 7. Enable continuous and programmable operator-controlled perfusion with volumetric flow rates ranging from 0.01 dyne/cm2 to 10 dyne/cm2 to the 3D bioprinted hydrogel tube (0.001 µL/min to 10 mL/min). 8. Use transparent top and bottom lid material that is optically compatible with microscopes (confocal, fluorescence and phase contrast). 9. Fit into conventional microscope specimen stage holder to allow real time visualization of the structure throughout the incubation period. 10. Include access ports enabling reservoir media change and sampling ports. 11. Use corrosion resistant, antimicrobial materials that can be easily assembled and disassembled for sterilization/disinfected for reusable applications.

Additional outcomes

The proposed solution should: 1. Have the ability to multiplex perfusion of multiple tubes (3 or more) in one bioreactor. 2. Provide continuous, automated and low-RPM rotation to each tube for uniform cell distribution. 3. Measure the viscosity, pressure, opacity and foam level of the media. 4. Have real-time ability to measure pH, dissolved oxygen (pO2), dissolved carbon dioxide (pCO¬2) level, glucose, and waste metabolites (i.e lactate) and other electrolytes in culture media.

Background and context The National Research Council – Human Health Therapeutics research center (NRC-HHT) is working to advance novel 3D bioprinting technologies to develop perfusable hollow tube blood vessels in support of a number of important applications in tissue engineering, regenerative medicine and drug discovery. Due to the complexity of the vasculature system, no current 2D or 3D in vitro models replicate the hemodynamic forces and blood flow, extracellular matrix milieu and geometry associated with blood vessels. The ability to 3D bioprint perfusable blood vessels, recapitulating this complex architecture, is key to overcoming these limitations and advancing key applications in drug discovery and tissue engineering. Towards this goal, HHT is leveraging novel and emerging 3D bioprinting technologies, such as the Aspect Biosystems RX1 microfluidic based bioprinter, to develop novel and more physiologically relevant vasculature models as a platform technology to support HHT’s pipeline of multi-functional bio-therapeutics that address unmet medical needs in neurological diseases and cancer. A successful bioprinting strategy is dependent upon the development of a specialized perfusable bioreactor platform that will enable the integration and perfusion of bioprinted vessels to support tissue maturation and in vitro assay development to assess vasculature permeability and drug delivery.