Osteochondral Implant Bioreactor
Osteochondral Implant Bioreactor
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Goal: Redesign benchtop bioreactor perfusion systems to scale production of tissue-engineered cartilage implants for clinical manufacturing.
Project Background Information
Project Background Information
Osteoarthritis in the knees can cause progressive loss of articular cartilage. Epibone produces an engineered allogenic osteochondral graft to repair damaged cartilage. Implants are cultured in the lab, eliminating risks of disease transmission and donor matching issues. The process involves placing bone marrow stem cells on a bovine scaffold, maturing them into cartilage cells through a proprietary technique, and then utilizing the living cartilage to treat various-size defects. Once implanted, the new graft has potential to mature and integrate with surrounding tissues.
Cartilage Graft Culture Workflow
Cartilage implants are matured in perfusion bioreactors within mechanical loading instruments that provide the cartilage surface with physical stimulation necessary for proper chondrogenic differentiation. Following Investigational New Drug (IND) clearance, perfusion bioreactor systems needed to be redesigned for clinical manufacturing. Benchtop models were only capable of producing a single graft after culture duration.
Skills
Skills
Project management
System design and rapid prototyping
Regulated manufacturing production
Feature development and verification (SolidWorks/MasterControl)
Timeline
Timeline
October 2023 - May 2024
Collaborators
Collaborators
Surgical stakeholders: Arthrex Medical
Internal development teams:
Engineering: 3 members
Research and Development: 5 members
Manufacturing: 4 members
System Overview
System Overview
Designed bioreactor perfusion systems with 3 internal teams and external medical device manufacturer.
System features:
Modular bioreactor units for independent assembly and harvest.
Fluid management system for priming individual unit tubing.
Shared media reservoir for batch sampling and media change.
Bioreactor system design schematic
CAD Bioreactor Cross-section
Modular Bioreactor Unit Design
Modular Bioreactor Unit Design
Utilized CAD (SolidWorks) and DFM to redesign perfusion bioreactors for clinical manufacturing.
Added filtered air vent to prevent internal chamber pressurization during culture allowing bioreactors to be operated at various heights above media reservoir (different incubator shelves).
Prototyped features with 3D printing and CNC milling of medical grade plastics following FDA 820.30 and ISO 13485 quality guidelines.
Component verification with precision height gauges and flow testing at full range of flowrates.
Modular Bioreactor Unit Fabrication
Modular Bioreactor Unit Fabrication
CAD Design
CNC Machining
Component verification
Graft Fixation/Release Redesign
Graft Fixation/Release Redesign
Addressed key manufacturing operator usability issue: cartilage damage from bioreactor loading.
Prototyped features with SLA 3D-printed FormLabs Biomed clear/elastic resin components.
Utilized flexible nature of PDMS to create clamping insert that positions and secures cartilage implant. Reduces operator error by ensuring graft is fully seated against bioreactor floor.
Designed plastic snap-fit clamp that engages walls to secure graft in PDMS insert. Clamp design eliminates screws for ease-of-use with gloves in aseptic environment.
Implant bioreactor loading frequently caused cartilage damage because of force/precision required.
Flexible PDMS graft insert design and protoype
Project Timeline
Project Timeline
Redesign bioreactor systems for scalable production within ISO 5 cleanroom environment.
Solve key functionality/usability issues in benchtop bioreactors for manufacturing operations.
Prototype system components and iterate on designs.
Produce/verify systems and ship to CDMO commercial manufacturing for phase I/II clinical trial.
Results
Results
Successfully designed, manufactured, and verified performance of implant perfusion systems for use in GMP manufacturing.
Newly developed scalable culture systems resulted in a 12x increase in implant manufacturing batch size.
Bioreactor implant loading feature improvements led to significant decrease in risk of nascent cartilage damage and 37.5% reduction in assembly time.
Provisional patent filed for bioreactors systems for use in maturation and preservation of osteochondral allografts.
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