Granular Bioink hydrogel for tissue bioprinting

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Every day in the United States, 17 people die while waiting for an organ transplant, and every nine minutes another person is added to the transplant waiting list, according to the Health Resources and Services Administration. One potential solution to address the shortage is to develop biomaterials that can be printed in three dimensions (3D) as complex organ shapes, capable of hosting cells and forming tissues. Attempts so far have failed, with so-called bulk hydrogel bioinks not integrating properly into the body and not supporting cells in thick tissue constructs.

Now, Penn State researchers have developed a new nanotechnology-based granular hydrogel bioink that uses self-assembled nanoparticles and hydrogel microparticles, or microgels, to achieve levels of porosity, shape fidelity, and cellular integration. never achieved before. The team published their approach in the journal Small.

“We have developed a novel granular hydrogel bioink for extrusion 3D bioprinting of microporous tissue-engineered scaffolds”, said corresponding author Amir Sheikhi, a Penn State assistant professor of chemical engineering who has a courtesy appointment in biomedical engineering. “We overcame previous limitations of 3D bioprinting granular hydrogels by reversibly linking the microgels using self-assembling nanoparticles. This enables fabrication of bioink granular hydrogel with well-retained microporosity, better printability and form fidelity.”

To date, the majority of bio-inks are based on bulk hydrogels – networks of polymers that can hold a large amount of water while retaining their structure – with nanoscale pores that limit cell interactions. -cell and cell-matrix as well as the transfer of oxygen and nutrients. They also require degradation and/or remodeling to allow cell infiltration and migration, delaying or inhibiting bioink-tissue integration. For more information, see the IDTechEx report on 3D bioprinting 2018 – 2028: technologies, markets, forecasts.

“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,” said Sheikhi. “Increasing hydrogel stiffness improves construct shape fidelity, but also reduces porosity, compromising cell viability.”

To overcome this problem, scientists in the field have started using microgels to assemble tissue-engineered scaffolds. Unlike bulk hydrogels, these granular hydrogel scaffolds were able to form 3D constructs in situ, regulate the porosity of the structures created, and decouple hydrogel stiffness from porosity. Cell viability and migration remained an issue, however, Sheikhi said. To achieve the positive characteristics during the 3D printing process, granular hydrogels must be tightly packed, compromising the space between the microgels and negatively impacting porosity, which in turn negatively impacts viability and cell motility.

The Penn State researchers’ approach addresses the problem of “blocking” while retaining the positive characteristics of granular hydrogels by increasing the adhesion of the microgels to each other. The microgels cling to each other, eliminating the need for tight packing due to interfacial self-assembly of adsorbed nanoparticles on the microgels and preserving microscale pores.

“Our work is based on the premise that nanoparticles can adsorb onto surfaces of polymeric microgels and reversibly adhere the microgels to each other, without filling the pores between the microgels”, said Sheikhi. “The reversible adhesion mechanism is based on heterogeneously charged nanoparticles that can impart dynamic bond to loosely packed microgels. Such dynamic bonds can form or break upon release or exertion of a shear force, allowing 3D bioprinting of microgel suspensions without packing them densely.”

Researchers say this technology can be extended to other granular platforms composed of synthetic, natural or hybrid polymeric microgels, which can be joined together using similar nanoparticles or other physical and/or chemical methods. , such as charge-induced reversible binding. , host-guest interactions or dynamic covalent bonds. According to Sheikhi, the researchers plan to explore how nanotechnology-based granular bioink could be further applied to tissue engineering and regeneration, on-chip organ/tissue/disease models, and in situ 3D bioprinting of organs.

“By addressing one of the persistent challenges in 3D bioprinting of granular hydrogels, our work could open new avenues in tissue engineering and functional organ printing,” said Sheikhi.

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