Uncovering the Healing Potential of Biorobotics

Scientists using human cells have introduced a way to create a multicellular, biological robot (or biobot), self-constructing, motile platform that in the lab had wound healing ability.

Called Anthrobots because of their human origin and biorobotics platform potential, each Anthrobot begins as a single cell, according to a recent paper.

The research offers glimpses into the eye-opening capabilities of cells, including how engineered cells could revolutionize efforts to create complex tissues for clinical applications in regenerative medicine and more. The research also suggests that leveraging morphogenetic tissue plasticity could enable development of “self-constructing living structures by design with predictable and programmable functional properties and numerous practical uses, greatly extending the current abilities of traditional fabrication practices in diverse fields as robotics…, architecture, sustainable construction, and even space exploration,” the authors wrote.

But we’re not there yet, according to the paper’s senior author, Michael Levin, PhD, a distinguished professor, Vannevar Bush chair of biology, and director of the Tufts Center for Regenerative and Developmental Biology at Tufts University in Boston, MA.

“It's still basic research, not yet clinical, and our furthest data are about its ability to repair nerve damage in vitro,” Levin told MD+DI. “Our current treatments are ‘low agency’ — drugs and implanted materials that are ‘dumb,’ in the sense that they don't make decisions or solve problems. They just do one thing, and we hope it's what we want, in the right amount.”

This is, however, the beginning of a new kind of medicine that uses cells and tissues, which are smart and have problem-solving competencies in physiological space, to help heal, Levin said.

A living device’s nuts and bolts

Levin and colleagues used human lung epithelium cells from adult donors of various ages and sexes in part because of the cells’ “cilia-powered locomotive abilities,” according to the study, as well as their ability to form organoids.

These scientists found that after they cultured the cells in an extra cellular matrix for two weeks and transferred them into a minimally viscous habitat, they prompted the organoids’ normally inward cilia to turn outward. The cilia became oar-like, driving what the researchers found were diverse motility patterns ranging from loops to lines and speeds from five to 50 microns.

“Anthrobots self-construct in vitro, via a fully scalable method that requires no external form-giving machinery, manual sculpting, or embryonic tissues and produces swarms of biobots in parallel,” according to the paper. “They move via cilia-driven propulsion…, living for 45 [to] 60 days.”

Anthrobots, they found, could interact with human tissue in the lab, moving across scratches in human neuronal monolayers and inducing gap closures.

What’s different?

This self-construction is a key differentiator. Early examples of biobots were hybrids of biological cells and supporting inert chemical substances. So, in addition to living cells, biobots were engineered cell lines with programmable features designed to use and intensify biological cells’ innate functionality.

Levin was senior author on a previous paper, which illustrated an approach resulting in “Xenobots, the first fully biological biobots created by sculpting or molding amphibian embryonic cells into multicellular structures that can spontaneously locomote without external pacing.”

In his latest research, Levin and colleagues wanted to address whether the capacity of genetically unaltered cells to generate a self-propelled, multicellular living structure was limited to amphibian embryonic cells, as well as whether such a living structure can be constructed by coaxing the initial seed cell to self-construct rather than having to individually sculpt or mold the structure.

The method Levin and colleagues used to produce the cilia-out spheroids from human airway epithelium was similar to one described by Boecking et al in which scientists grew airway organoids embedded in a collagen-rich matrix and cultured them in air-liquid-interface inserts.

“After this initial [air-liquid-interface] culture period of 14 days, the mature airway organoids are dissolved from the collagen matrix and replated into a fresh same matrix of similar composition (to remove catabolites) for another 14 days. It is in this second 14-day period that cilia localization on the surface is accomplished by administering R-Spondin-2 (RSPO2) and Noggin into the matrix,” according to the paper by Levin et al.

Levin and colleagues used the initial proliferation of individual normal human bronchial epithelials into spheroids with cilia-lined lumen by culturing them as embedded in a gel-based matrix.

“However, in our method, upon dissolution of spheroids from matrix at the end of this 14-day period, the cilia-in spheroids are not plated back into the matrix, and instead, the cilia localization into the spheroid cortex is achieved by culturing these spheroids in low-adhesive environments,” according to the paper.

Levin and coauthors observed cilia localization within one week, which makes their method faster and less laborious than that of Boecking et al.

Many questions still remain, including what other cells can make Anthrobots?

Biotech company Astonishing Labs helped to fund this research. The company, according to news on Science.org, plans to use the technology to treat neurological disease and nerve and spinal cord injuries, as well as to help heal burns.