Engineering Thermostable Gelatin Methacryloyl Granular Bioinks For In Situ Bioprinting
Restricted (Penn State Only)
- Author:
- Castro, Angie
- Graduate Program:
- Chemical Engineering
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- June 17, 2024
- Committee Members:
- Amir Sheikhi, Thesis Advisor/Co-Advisor
Bryan D Vogt, Committee Member
Robert Rioux, Professor in Charge/Director of Graduate Studies
Andrew Zydney, Committee Member - Keywords:
- bioprinting
GelMA
hydrogels - Abstract:
- Gelatin methacryloyl (GelMA) is a widely used biomaterial to partially mimic the extracellular matrix (ECM), promote cell activities, and enable tissue regeneration. Its crosslinkable vinyl functional groups allow for tunable mechanical properties, making it suitable for various tissue engineering applications; however, bulk GelMA hydrogel faces challenges for its application in extrusion based bioprinting (EBB). In bulk hydrogels, made up of crosslinked polymers, the stiffness is coupled with the porosity, introducing a trade-off between shape fidelity (requiring a higher stiffness) and cell viability (requiring a lower stiffness/higher pore size) in bioprinted constructs. To address this challenge, GelMA hydrogel microparticles (microgels) may be used as building blocks in a bioink to build constructs with microscale interconnected void spaces. In this way, the microgel stiffness is decoupled from the construct porosity, improving cell infiltration and viability. GelMA microgels combined with EBB platforms offer a method to construct complex tissue-mimetic structures through precise spatial control and enhanced cellular functions. However, physically crosslinked GelMA microgels must be maintained below the sol-gel transition temperature of gelatin (ranging from 25°C to 30°C), limiting their potential for in situ biofabrication. Here, we develop thermostable GelMA microgels paired with heterogeneously charged nanoparticles (NPs) to form GelMA granular bioinks, which are capable of in situ forming porous scaffolds via extrusion bioprinting. GelMA microgels were fabricated using a step emulsification microfluidic device and stabilized through partial photocrosslinking, rendering them stable at the physiological temperature (37°C) while maintaining enough unreacted vinyl groups to form stable crosslinked structures after 3D bioprinting. Reversible self-assembly of the NPs on the thermostable microgel surfaces enhance microgel-microgel interactions, yielding a shear-thinning composite nanoengineered granular bioink (NGB). This platform enables the in situ biofabrication of porous granular GelMA constructs.