Goal: Design hybrid culture/testing instrumentation platform for pre-clinical surgical evaluation of 3D-printed artificial lung tissue scaffolds.
The mission of Lung Biotechnology is to manufacture an unlimited supply of transplantable organs before the end of the decade using next-generation 3D-printing and cellularization techniques. Hydrogel tissue scaffolds are printed using custom developed SLA 3D-printers and proprietary bioink resin formulations. Human small airway epithelial cells are cultured on hydrogel surfaces to create multivascular network. Efficacy is evaluated in benchtop testing and functional animal testing (rabbit/pig) for gas exchange quantification.
3D-printed lung scaffold scaffold
Culture systems for properly securing hydrogel scaffolds were needed for proper cell culture and surgical testing.
Key Challenges
Model complexity (10um capillary diameter, 100um capillary airway interface)
Hydrogel scaffold robustness
Complex cellularization task
Previous methods of support and transportation for animal testing of hydrogel organs
Product evaluation with pre-clinical animal surgeons using porcine models.
CAD (SolidWorks/OnShape).
Rapid SLA 3D-print prototyping
Creative problem solving for novel materials.
May - October 2022
External engineering: 3D Systems
Surgical stakeholders: Revivacor
Internal development teams:
Engineering: 4 members
Research and development: 4 members
Component exploded: Silicone guide wires used to stabilize hydrogel scaffolds during cell culture.
1L Pyrex lab bottle with GLS80® standard lid
Key Design Specifications:
Standardized GLS80® 1L bottle housing
Must suspend hydrogel scaffold securely without damage
Rollable for cellularization (lock hydrogel scaffold into axially-aligned plane)
Testable vertically/horizontally
Autoclavable
Scalable manufacturing
Quick operation and functional alignment (nozzles/etc.)
Biocompatible materials
Surgical Platform Evaluation (OR)
Bioreactor Parts:
Silicone hammock wire cage
Axial anchor
Lid insert
Materials:
0.162” 316L steel wire
FormLabs Surgical Guide/Biocompatible Resin
0.5 mm silicone sheet
Device Operation Workflow:
Drop anchor into bottle
Close device around lobe and seat into bottle
Insert nozzle with tubes aligned and seal bioreactor with blue ring
Prototype device with hydrogel scaffold
Methods
Developed cage assembly using off-the shelf parts (McMaster) and SLA 3D-printed plastic components.
Integrated custom 180° roller using DC motor and microcontroller.
Assembly
Bend pre-cut rods using custom tools
Print parts and thread setscrew holes
Cut silicone bands and poke holes
Assemble device
Successfully secured, perfused, and and grew hydrogel organ tissue with human small airway epithelial cells. Tissue achieved functional vascularization during cell culture with developed bottle rollers.
Concluded initial surgical extra corporeal lung perfusion study evaluating hydrogel organ function. Two pig surgeries successfully completed without device leakage or malfunction.
Initial product validation with collaboraters: surgical team, cell culture, engineering.