Amir Sheikhi
Nittany Lion logo printed with the new bioink
There are 17 deaths daily in the United States of people waiting for an organ transplant. As well as this, a person is added to the waiting list every nine minutes, according to the Health Resources and Services Administration.
Biomaterials that can be 3D printed into complex organs shapes that are capable of hosting cells and forming tissues is a potential solution to alleviate the shortage. Attempts so far have fallen short. What are referred to as bulk hydrogel bioinks fail to integrate into the body properly and support cells in thick tissue constructs.
Researchers at Pennsylvania State University have made a potential breakthrough in this area. The team has developed a novel nanoengineered granular hydrogel bioink that makes use of self-assembling nanoparticles and hydrogel microparticles, or microgels. The team says the bioink achieves previously unattained levels of porosity, shape fidelity and cell integration.
“We have developed a novel granular hydrogel bioink for the 3D-extrusion bioprinting of tissue engineering microporous Scaffolds,” said author Amir Sheikhi, Penn State Assistant Professor of Chemical Engineering, who has a courtesy appointment in biomedical engineering.
Sheikhi continued: “We have overcome the previous limitations of 3D bioprinting granular hydrogels by reversibly binding the microgels using nanoparticles that self-assemble. This enables the fabrication of granular hydrogel bioink with well-preserved microporosity, enhanced printability and shape fidelity.”
The majority of bioinks up to this point have been based on bulk hydrogels, which are polymer networks able to hold a large amount of water while maintaining their structure. They contain nanoscale pores that limit cell-cell and cell-matrix interactions as well as oxygen and nutrient transfer.
The polymer networks also required degradation and/or remodelling to allow cell infiltration and migration, delaying or inhibiting bioink-tissue integration.
“The main limitation of 3D bioprinting using conventional bulk hydrogel bioinks is the trade-off between shape fidelity and cell viability, which is regulated by hydrogel stiffness and porosity,” Sheikhi said. “Increasing the hydrogel stiffness improves the construct shape fidelity, but it also reduces porosity, compromising cell viability.”
Amir Sheikhi
Scientists in the field attempted to tackle this issue by using microgels to assemble tissue-engineering scaffolds. The scaffolds were able to regulate the porosity of the created structures, but cell viability and migration remained an issue.
The researchers from Penn State approached the issue while maintaining the positives of granular hydrogels by increasing the stickiness of microgels to each other. The microgels cling to each other which removes the need for the tight packing together, as a result of interfacial self-assembly of nanoparticles adsorbed to microgels and preserving microscale pores.
Sheiki said: “The reversible adhesion mechanism is based on heterogeneously charged nanoparticles that can impart dynamic bonding to loosely packed microgels. Such dynamic bonds may form or break upon release or exertion of shear force, enabling the 3D bioprintability of microgel suspensions without densely packing them.”
The researchers plan to explore how the newly nanoengineered bioink can be further applied for tissue engineering and regeneration, models of organs and possibly in situ 3D bioprinting of organs (the direct printing of bioinks to create or repair at a defect site).
Amir Sheikhi
Amir Sheikhi
The journal Advanced Materials named Sheikhi as a Rising Star for the study. Other authors of the paper include chemical engineering doctoral students Zaman Ataie and Sina Kheirabadi; chemical engineering undergraduates Rhea Jiang and Carter Petrosky; mechanical engineering and biomedical engineering undergraduate Christian Vollberg; mechanical engineering undergraduate Jenna Wanjing Zhang; and biomedical engineering undergraduate Alexander Kedzierski.
The research was partially funded by the Penn State Living Multifunctional Materials Collaborative Research Seed Grant Program, the Penn State Material Research Institute and the College of Engineering’s Materials Matter at the Human Level seed grants.
Read more about other uses of 3D printing at Penn State here.
Dr. Jia Min Lee and Dr. Wai Yee Yeong from Nanyang Technological University in Singapore wrote for TCT earlier this year, explaining 3D bioprinting and what could potentially be achieved in the future with the technology.
