All engineers are familiar with the concept of assembling modular base units into complex multi-part systems. When it comes to building with “traditional” materials (i.e. metals, polymers, etc.), we have optimized the manufacturing tools and design rules required to generate the final form and function required of a system. Building complex multi-part systems with the base unit of living organisms, the cell, is not quite the same – but it has the potential to be!

The idea of “building with biology” spurred the growth of the field of biofabrication, aided by enabling technologies such as 3D bio-printing and inspired by the potential of tissue engineering and regenerative medicine. While this discipline has had (and will continue to have) tremendous clinical impact, it does leave some unexplored areas for future discovery.

Biofabrication has, for the most part, centered on reverse engineering what already exists in the body. As a field, we have imitated the “form” of tissues/organs to the best of our manufacturing ability, and done our best to ensure that “function” will follow. When seeking to replace diseased or damaged tissues and organs, this is an appropriate and efficient approach, and has generated much success.

However, there is no reason for us to restrict ourselves purely to reverse engineering when the opportunity to forward engineer non-natural forms and functions also exists. With a supply of biological materials and access to manufacturing tools that can build with such materials, we have added a new class of materials to every engineer’s toolbox and can start building beyond biology.

Why do this? To harness the dynamic response behaviors programmed into living cells – their ability to adapt to their surrounding environment in real-time. Creating machines and systems that can adaptively respond in the same way could greatly enhance our ability to tackle grand engineering challenges.

Has this been done? Examples of bio-hybrid machines have largely focused on examples of force production and locomotion, driven by primary cardiac muscle or tissue engineered skeletal muscle. A detailed protocol for building a walking bio-hybrid robot (bio-bot) powered by modular skeletal muscle bioactuators, the product of my PhD, was recently featured on the cover of Nature Protocols.

How do we teach this? Training the next generation of engineers and scientists to incorporate biological materials into the machines they design is not an easy feat, but thankfully one for which there are established precedents. Drawing inspiration from the experiential, team-based, and project based learning approaches presented in the education literature, I have worked with collaborators to establish an undergraduate course in this field. The final project involves student teams designing and building their own muscle-powered bio-hybrid machines.

What challenges remain? We don’t completely understand the design rules for building with biological materials in the same way we do for synthetic materials. This adds a layer of difficulty to bio-hybrid forward design – we must first uncover the basic rules of multi-cellular assembly and interaction from the micro- to the macro-scale, and then apply them. Whether we do this most effectively via computational modeling, conversations with basic scientists and clinicians, experimental trial and error, or some combination thereof remains to be seen.

To conclude, the “bio-hybrid revolution” is very new, growing rapidly, and has tremendous future potential. A coordinated multi-disciplinary approach promises to provide us with the tools, materials, and procedures required to build with living materials in the same way we have learned to build with synthetic materials. Perhaps the most important part of the puzzle, developing a standard of ethical practice for “building beyond biology”, will require a thorough investigation of the needs and motivations of all the relevant stakeholders (and is hence worthy of a blog post all its own). As a newly minted engineer, I am thrilled to be joining and contributing to the bio-hybrid revolution.

Acknowledgements

Thank you to Janet Sinn-Hanlon for generating the bio-bot schematic used in the poster image.

References

Raman, R., Cvetkovic, C. and Bashir, R., 2017. A modular approach to the design, fabrication, and characterization of muscle-powered biological machines. Nature Protocols, 12(3), pp.519-533.

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