[Paper Review] Biohybrid robotics with living cell actuation

 

 

 

Biohybrid robotics with living cell actuation 

https://pubs.rsc.org/en/content/articlelanding/2020/cs/d0cs00120a

Biohybrid robotics with living cell actuation

 

 

 

 

 

 

• As simulators of organisms in Nature, soft robots have been developed over the past few decades. In particular, biohybrid robots constructed by integrating living cells with soft materials demonstrate the unique advantage of simulating the construction and functions of human tissues or organs, thus attracting extensive attention and research interest.
• Here, we present up-to-date studies concerning biohybrid robots with various biological actuators such as contractile cells and microorganisms. After presenting the basic components including biological components and synthetic materials, the controlling methods and locomotion(운동) modalities of biohybrid robots are clarified and summarized.
• We then focus on the applications, especially the biomedical applications, of the biohybrid robots including drug delivery, bioimaging, and tissue engineering. The challenges and prospects for the future development of biohybrid robots are also presented.

 

 

 

Introduction 

• Among the soft robotics, biohybrid robots constructed by the integration of living cells and flexible materials have reproduced similar organ or tissue construction and functions of organisms, and this integration is attributed to the progress of manufacturing technologies and advances in tissue engineering.
• Compared with traditional dynamical devices, biological actuators exhibit superiority in terms of intrinsic softness, environmental safety and compatibility, remarkable energy conversion efficiency, and integrated sensing and control. By employing biological components including contractile(수축성의) living tissues and microorganisms as actuators, together with effective microstructure design, biohybrid robots have realized various human like biomimetic behaviours and functions.
• In general, biohybrid robots can mimic anisotropic(비등방성) microstructures in vivo and exhibit tissue or organ functions similar to those of humans, thus becoming a novel research area because of their great potential in the biomedical field.
• Here, we present a comprehensive review of relevant research studies on biohybrid robotics with actuation of biological impetuses(자극). In Nature, organisms exhibit favourable softness and high energy-conversion efficiency, which are desirable for the fabrication of new-generation robots.
• In this review, we discuss the latest research on biohybrid robotics with various biological impetuses. After presenting the basic components, we introduce the construction of biohybrid robots, including the manufacturing methods of materials and their integration with living tissues. Subsequently, the controlling mechanisms of biohybrid robots and their present movement modes are discussed. Examples of typical biohybrid robots are also presented. Emphasis is given to the description of the applications of biohybrid robots in the biomedical field. Finally, we propose some challenges in exploiting these new-generation robots and their future prospects.

 

 

 

Basic components of the biohybrid robotics

2.1 Biological components

• Actuation is the most fundamental and indispensable element speaking of robots. Despite increasing attention being paid to the biocompatibility and biomedical applications of robots, most of the conventional actuators failed to meet the requirements of miniaturization and efficiency.
• Therefore, novel actuators with high flexibility and driving force are greatly anticipated. Nature is an ideal resource library to solve this problem because it has evolved various cells that can generate desired forces for actuation.
• Universal biological components include cardiomyocytes, skeletal muscles and microorganisms, and their employment promotes the evolution of biohybrid robots from the laboratory level to clinical stage.

1. Cardiomyocytes - can generate enough contraction force to support the movement of biohybrid robots.

2. Skeleton muscles - energy supply from ATP / more powerful and rapid / easy to manipulate their performance 

3. Microorganisms - controllability and directional movement 

4. Others - T cells - power sources for biohybrid robots / Dorsal Vessel tissues / neurons - effective actuators 

 

 

 

2.2 Synthetic materials for biohybrid robots

• Another essential part of biohybrid robots is synthetic materials. Since the biological components are directly cultured on the engineered synthetic materials to construct adaptive and biomimetic biohybrid robots, the synthetic materials are supposed to meet several requirements of favourable biocompatibility, flexible properties, tunable microstructures, etc.
• Popular substrate materials for the construction of biohybrid robots include PDMS, hydrogels, protein materials, metals and silicon products.14 In order to improve the performance of resultant biohybrid robots, the materials are usually designed with asymmetric structures to mimic the physiological environment and specific shapes to reduce resistance by using a 3D printing technique, a template assisted method, an etching approach and so on.

 

 

 

Controlling methods of biohybrid robotics

• Although biohybrid robots driven by living cells show the advantage of autonomous and efficient motion ability, their behaviour and capability to accomplish precise tasks could be further promoted by introducing external stimulations. So far, various power sources such as light, electrical signals, chemical compounds and magnetic fields have been investigated and improved. With these interventions, biohybrid robots could thus demonstrate various locomotion modalities under human command.

 

3.1 Stimulations

• Most of the biological components such as bacteria are intrinsically capable of responding to stimulations including electrical, optical, chemical and magnetic signals. Based on these intrinsic characteristics, together with the integration of control pathways, researchers have been developing biohybrid systems with controllable motion under different stimulations.

1. Optical Stimulation - photo-controllable properties 

* healing protocol - recover the funtionality of damaged optogenetic skeletal muscle bioactuators within two days 

* The heat generated by optical stimulation and some specific light sources may damage the biological components.

2. Electirical Stimulation - sequential electrical pulses generated from electrodes located at the edges of the tissues. 

3. Chemical Stimulation - chemical reagents can induce a specific behavior of bacteria

- chemical stimulation usually depends on the administration of chemicals into the culture environment to control the behaviour of biohybrid robots, with the disadvantage of poor spatial and temporal resolution owing to diffusivity.

4. Magnetic Stimulation 

 

 

3.2 Locomotion modalities 

- Swimming / Walking / Pumping - heart is a powerful tissue that pumps blood to all parts of the body 

- Because of their automatic beating capability, contractile cardiomyocytes are the first choice to serve as actuators

 

 

 

Perspectives and conclusions

• In this review, we have presented a comprehensive summary of the latest progress in biohybrid robotics, involving the development of their basic components, controlling methods, and preliminary applications. With considerable efforts of researchers, biohybrid robotics is experiencing a rapid and significant revolution, which may significantly affect various areas, including the biological, medical, and engineering fields.
• Despite great progress that has been made in the field of biohybrid robots, there are still challenges impeding laboratory research from solving the problems of the real world.
• Therefore, several important issues need to be considered and addressed during the technological development of biohybrid robotics.
  • First, the biological components of biohybrid robots need to be discussed. At present, the available cell sources are too limited to satisfy the increasing research demand. Stem cell technology is an effective way to solve this problem, and using this technology can also avoid the ethical issues and complex animal extraction processes. Although relevant stem cell differentiation protocols were developed decades ago, the current cost is still expensive and the technology cannot meet large market demands.
  • In addition, the lifetimes of most biohybrid robots are extremely short. To our knowledge, the maintenance of the movement capability of biohybrid robots cannot exceed months, which affects their practical application value, while organisms can solve this problem well. Therefore, it is necessary to search for methods that can produce long-term cell culture or even realize cell immortalization by drawing inspiration from Nature.
    
    
  • The second issue refers to the performance optimization of soft materials. To maintain the movement properties of biohybrid robots, materials should satisfy the requirements of favourable biocompatibility, stability, durability, and flexibility.
  • Although various soft materials have been widely utilized to construct biohybrid robots, these materials still have difficulty in effectively providing similar environments to those provided by organisms to induce the orientation or differentiation of cells. With this in mind, material science and manufacturing techniques should be combined more tightly to fabricate more advanced soft materials with bioinspired morphology and functionality design.
    
    
  • The third issue concerns the construction of biological systems. Virtually all biohybrid robots are cultured and tested in a liquid environment, greatly restricting their practical applications. Although attempts have been made to encapsulate biological entities in a sealed medium for atmospheric operation, the constructed biohybrid system could just maintain vitality for days.
  • Therefore, establishing a built-in circulation system or bionic vascular network similar to that of humans is a promising development direction for biohybrid robots to realize effective separation from the culture medium environment.
  • In addition, responsive elements and artificial intelligence should also be integrated into robotic systems to realize controllable or even autonomous behaviour. In this case, the circulation process could be manipulated by optical or electrical signal interference to ensure the stability of biohybrid robots.
  • Besides, the biohybrid robots based on co-culture systems of multiple cell lines have seldom been explored, although they have significance in reproducing all main muscle interfaces in vitro.
  • In addition, the majority of current biohybrid robots have been engineered to perform a single function. In fact, the prospects of robotics lie in constructing complex systems that can carry out useful tasks, which require the possession of multiple functions to adapt to different environments. In this regard, the versatility of biohybrid robots should be investigated and developed. 
• In summary, biohybrid robots demonstrate outstanding properties and possess practical potential in a wide range of fields. Future endeavours could be focused on improving the performance of biohybrid robotics and investigating their applications in biological and medical fields.
• We hope that this review will inspire researchers in this multidisciplinary area to address the issues mentioned above and to promote the development of biohybrid robotics. We firmly believe that more enormous and exciting achievements of biohybrid robotics will be accomplished in the future.