Assembling organ building blocks (OBBs) will become a viable method to create human tissue to fill the gaps in organ donation. But, despite more than two decades of work, it most projects aren’t ready for commercial manufacturing.

“There’s a level of complexity that needs to occur for the cells to come together as a tissue,” notes Michael J. Yost, PhD, vice chairman of surgery for research and the interim executive director of the Medical University of South Carolina (MUSC) Foundation for Research Development. None-the-less, “Bioprinting grafts isn’t that far away…maybe five to eight years.”

Bioprinting functional organs is much further in the future. “The leap from printing a graft to printing an organ will be formidable,” he cautions.

“OBBs composed of multicellular spheroids, organoids, and assembloids offer an important pathway for creating organ-specific tissues with the desired cellular-to-tissue-level organization,” Jennifer Lewis and colleagues point out in a recent paper. Organ biomanufacturing is a two-step process. First develop functional units with all the necessary cellular components, and then assemble them into organ-specific tissue complete with vasculature.

Challenges include cell sourcing, vascularization, maturation, function, standards development, and clinical translation, as well as the self-assembly of the tissue blocks. The most immediate challenges, however, may be establishing vascularization and overcoming the immune system’s rejection.

“When we put a graft on a tissue bed (even an autologous graft) the body perceives that as different and mounts an innate inflammatory response,” Yost says. The challenge (and the focus of much of his research) is to communicate with the patient’s immune system so it allows the tissue to engraft and still maintain its full response capability” to respond to pathogen. “We haven’t gotten around that yet.

“We’re making incremental progress,” Yost says, but much remains to be done. For example, “The depth and breadth of expertise needed for vascularization is formidable.” There also is incomplete understanding of the overlap and intersection of certain needed fields, including structural engineering, chemistry, vascular biology, tissue skeletal biology, and immunology.

A handful of biotech companies are pioneering the field. Humacyte may be the furthest along, with products in Phase III clinical trials. Its stem-cell-based approach is yielding engineered arteries that can be grafted into a patient with only a minimal immune response.

“That’s a viable approach, but it’s just a steppingstone along the way,” Yost says.

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