Tissue Engineering Based Bio-Electromechanical Hybrid Robotic Systems for Biomedical Applications

基於組織工程的生物機電混合系統及其在生物醫學方面的應用

Student thesis: Doctoral Thesis

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Award date3 Jan 2018

Abstract

Modern medical development relies on combining different types of robotic systems to provide complex therapeutic operations, during which tissue-engineering based bio-hybrid systems present inherent biological advantages in signal interaction, self-sustainability, and environment adaption. However, it is still a challenge to implement those systems for different medical applications, with issues including deficient electricity supplies, limited functions, and non-bioactive interfaces. This dissertation presents a series of bio-hybrid systems that integrate tissue-engineered, active elements with mechanical or electronic interfaces, with the aim of addressing these bottlenecks and promoting the development of the next generation of bio-hybrid medical systems.

First, in chapter 2, a bio-hybrid device called a “cell generator” is explored to address the electricity supply issue to tissue-engineered, medical machines. The controllable, cell-based machine can harvest energy from the natural dynamics in the bioactive, living environment to generate electricity for various biomedical applications, overcoming the drawbacks of existing toxic, non-biodegradable, and unsustainable powering techniques. The “cell generator” device is based on an array of piezoelectric microcantilevers wrapped in three-dimensionally patterned cardiac cells. The spontaneous contraction of the engineered cardiac constructs provides a mechanical energy source for electricity generation. We demonstrate that a single “cell generator” unit with 40 cantilevers can output peak voltages of ~70 mV, and a larger array of 540 cantilevers can directly generate a pulsed output as high as ~1 V. When integrated with an electrical rectification and storage circuit, we further demonstrate that the “cell generator” can provide functional outputs and work as a self-powered neural stimulator to evoke action potentials in cultured, neuronal networks. This demonstration of “cell generator” technology provides an innovative perspective of exploiting live, biological powering systems for biomedical, micro-scale, robotic devices in the human body.

Moreover, to achieve multiple functions on the bio-hybrid devices, a novel concept of a transformable robot is proposed in chapter 3. A tissue-engineered, floating-plane robot is demonstrated, and its motion functions can be remotely controlled by transforming the mechanical structure in response to near-infrared stimuli. By emulating the swimming of whales, the floating-plane robot is actuated by a “muscular tail-fin,” which works as a cellular engine powered by the synchronized contraction of striated, cardiac microtissues cultured on a flexible membrane. For transition from a moving to a stationary state, the robot is optically triggered to transform from a spread to a retracted form, thus minimizing the propulsion output from the “tail-fin” and effectively switching “off” the cellular engine. The cyclic, programmable transformation relies on a heterogeneously structured, photosensitive hydrogel, which can be induced to deform within a few seconds by near infrared (NIR) irradiation. The response rate is almost two orders of magnitude faster than existing shape-tunable hydrogel materials, thus empowering an instant transformation process for the floating-plane robot. This new concept of a bio-hybrid transformer robot and its realization will open a promising pathway for the development of multi-functional and intelligent soft robotic systems.

In addition, in chapter 4, to enhance the sensitivity and efficiency of the tissue-engineered robotic systems in medical diagnostics and signal exchange, a promising two-dimensional material, MXene, is explored to act as a bioactive interface for biosensing applications. Based on the ultrathin, conductive MXene micropatterns, simple and effective MXene field-effect transistors (FETs) are fabricated and employed to perform the highly sensitive, label-free detection of dopamine, as well as to monitor spiking activity in primary hippocampal neurons. The MXene FET biosensor is well compatible with neuron cells in long-term cultures, presenting a high sensitivity to detecting neurotransmitters and probing neural activity in primary hippocampal neurons. The excellent features of the MXene materials guarantee good interfacing of neuron cells with the electronic components in the system, which enable the real-time, label-free monitoring of neuronal spiking activities. Meanwhile, the transparent, ultrathin layers of MXene micropatterns do not interfere with traditional, optical, microscopic observation of the cells, so that calcium imaging for neural activity can be simultaneously conducted and compared with electrical measurements using MXene FETs. The excellent performance of the MXene FET makes it a potential candidate for acting as a bio-electrical interface for the tissue-engineered robotic systems, which would improve the efficiency of extensive medical operations, including implant-based, in situ monitoring; drug delivering; and muscular or neural stimulation.

In summary, the presented studies explore three different bio-hybrid systems, spanning from a “cell generator” and a “cell transformer” to an “MXene-biosensor,” with the goal of improving the functionality and efficiency of the tissue-engineering-based medical devices, which would largely optimize disease diagnose/treatment processes and promote the fabrication of self-sustaining medical devices. The qualitative and quantitative results established in these studies may lead to the development of novel investigative and therapeutic devices integrated with biological, active components.

    Research areas

  • Tissue engineering, bio-hybrid system, medical applications