Paralyzed rats with spinal cord injury were implanted with degradable 3D piezoelectric scaffolds and ultrasound excitation was used to achieve wireless and controlled electrical stimulation, thereby promoting the repair of their spinal cord injuries.
This is not a fantasy, but the result of a realistic experiment. The reviewer commented on the study: "In the body electrical stimulation has important application prospects in tissue engineering, the new concept of ultrasound combined with degradable piezoelectric scaffold to achieve controlled in vivo electrical stimulation is very meaningful. ”
This is undoubtedly good news for regenerative medicine, so how does it do it?
Fig. 丨Wireless electrical stimulation based on biodegradable 3D piezoelectric scaffold promotes spinal cord injury repair. (Source: ACS Nano)
Recently, a team from Huazhong University of Science and Technology and Wuhan University of Technology developed a biodegradable 3D piezoelectric scaffold that uses programmable ultrasound to control its function in vivo electrical stimulation wirelessly and wirelessly.
In addition, they also successfully verified that the 3D piezoelectric scaffold has a significant repair function for rat spinal cord injury in related experiments in rat models, showing a new solution for the in vivo electrical stimulation protocol of regenerative medicine.
Recently, a related paper was published in ACS under the title "Wirelessly Powered Electrical-Stimulation Based on Biodegradable 3D Piezoelectric Scaffolds Promotes the Spinal Cord Injury Repair" Nano on [1].
Related papers (Source: ACS Nano)
The first author of the paper is Chen Ping, a doctoral student at Huazhong University of Science and Technology, and the co-corresponding authors of the paper are Professor Luo Zhiqiang, School of Life Science and Technology, Huazhong University of Science and Technology, and Professor Dai Honglian, State Key Laboratory of Composite New Technologies of Wuhan University of Technology.
The "3-in-1" function of the 3D piezoelectric bracket
The team used electrospinning to prepare polylactic acid nanofibers and potassium sodium niobate nanowires into 3D piezoelectric scaffolds, which realized the functional "three-in-one" on the same piezoelectric biomaterial, that is, it simultaneously satisfies the biodegradability, controllable electrical stimulation function and tissue engineering porous scaffold function of the material.
In fact, the research on the use of electrical stimulation in tissue repair processes has received widespread attention at home and abroad. However, most studies involve implanted electrodes being led out of the skin and using electrical stimulation equipment in vitro to conduct related studies.
In essence, the "wireless and controllable" technology to achieve in-body electrical stimulation is the highlight of the research, and the key point is the programmable control of ultrasound. In other words, the user can independently control the time node, stimulation duration, and stimulation intensity of electrical stimulation according to demand.
GIF丨Walking test after spinal cord injury repair in rats (Source: Huazhong University of Science and Technology)
In experiments, the researchers found that wireless electrical stimulation based on ultrasound drive and 3D piezoelectric nanofibers can differentiate neural stem cells into neurons in vitro. At the same time, in vivo studies have shown that in vivo electrical stimulation provided by this 3D piezoelectric stent favors motor recovery and promotes spinal cord injury repair if appropriate ultrasound irradiation is performed.
It is reported that the study lasted two and a half years, based on the team's previous research results on ultrasound-inspired peripheral nerve-controllable electrical stimulation of implantable nanogenerators in the field of tissue engineering neurorepair.
In general, the use of piezoelectric materials for neurorepair has been reported, and the team members found that potassium sodium niobate nanowire piezoelectric materials have good biodegradability and biocompatibility in related research.
Therefore, they further asked, can degradable high-performance piezoelectric materials be used for nerve repair? Therefore, in addition to studying the application of neuromodulation, they also tried to study the neurorepair of piezoelectric materials.
Figure丨3D piezoelectric scaffolds combined with ultrasound-excited to promote repair of spinal cord injury areas (Source: ACS Nano)
The team carried out independent research and development in programmable ultrasound, built a miniaturized ultrasonic excitation and control device suitable for tissue engineering applications, and realized wireless and controllable in vivo electrical stimulation by using programmable ultrasound combined with degradable 3D piezoelectric scaffolds.
Professor Luo Zhiqiang said: "The immunomodulatory effect of electrical stimulation in vivo is another unexpected finding in this study. As a follow-up to this work, we are investigating the importance of electrical stimulation in regulating immunity, including its role in repair processes such as myocardium, nerves, and bone tissue. ”
New treatment options for regenerative medicine
The 3D piezoelectric scaffold in this study has excellent piezoelectric properties and provides new ideas for regenerative medicine. Specifically, the application potential of this technology lies in the following three aspects:
First, applications in electronic medicine, such as wireless deep brain stimulation for Parkinson's disease or vagus nerve stimulation for inflammation through ultrasound excitation.
Second, in vivo electrical stimulation for tissue repair, such as repair of tissues such as nerves and myocardium. In addition, immunomodulation in vivo electrical stimulation also has potential applications.
Third, the use of wireless electricity to stimulate the controlled and slow release of drugs.
Professor Law graduated from the Department of Physics at Nanyang Technological University in Singapore and engaged in postdoctoral research on organic electronic devices and bioelectronic devices in the Department of Chemistry at the University of Chicago. In 2016, he returned to China to join the School of Life Science and Technology of Huazhong University of Science and Technology to establish an independent research group, whose main research direction is bioelectronic materials and devices.
It is understood that the current research direction of Professor Luo Zhiqiang's team is neural engineering electronic materials and devices, including materials and devices used in neuromodulation and neural tissue engineering, such as the use of implantable miniature electronic devices for neuromodulation to treat Parkinson's disease, and electroactive biomaterials for the repair of peripheral nerves and spinal nerves.
In addition, they are actively working with other teams to explore the aspects of cardiovascular tissue engineering and bone tissue engineering in body electrical stimulation.
Group photo of some members of Professor Luo Zhiqiang's team (Source: Luo Zhiqiang)
The research group recently used ultrasonic technology and implantable piezoelectric materials to solve the problem of wireless in vivo electrical stimulation, which laid a good foundation for this new research [2,3].
Previously, they comprehensively analyzed motor function recovery and histological evaluation studies, confirmed that ultrasound-driven in vivo electrical stimulation is beneficial to promote neural regeneration, and provided a new strategy for using ultrasound to respond to biodegradable piezoelectric nanopower materials and devices to deliver electrical stimulation in vivo in tissue engineering.
In addition, the team previously developed an implantable piezoelectric thin-film nanogenerator that promotes peripheral nerve repair through ultrasound-driven electrical stimulation, a device that can respond to programmable external energy sources in real time.
In terms of clinical collaboration, the team is working with clinicians and has developed a variety of electrical stimulation protocols, and related research is ongoing. At the same time, the team also said that they will continue to pay attention to issues such as the power generation capacity of functional materials, the controllability of electrical stimulation and the biodegradability of materials.
Figure丨 Electrical stimulation in the body helps to recover from exercise and promote the repair of spinal cord injury areas (Source: ACS Nano)
It is worth noting that the 3D piezoelectric scaffold in this study is non-toxic and harmless in the composition of potassium sodium niobate. The team demonstrated the promising possibilities of 3D piezoelectric scaffolds in spinal cord repair, and one of the issues that cannot be ignored if it is promoted to the clinic in the future is that the degradation process of niobium and whether its metabolism is chronic and other details need to be further explored.
Luo Zhiqiang also believes that some more friendly biological piezoelectric materials, such as piezoelectric proteins, may be one of the better research directions, and his team is also exploring in this direction. He pointed out that how to improve the performance of piezoelectric proteins while also achieving slow degradation and other series of problems are the direction he and his team want to further explore.
The next step is for the team to collaborate with the stem cell team, hoping to use this technology in combination with induced pluripotent stem cells for adjuvant therapy for spinal cord injury repair.
"Our earlier studies through controlled electrical stimulation found that immune regulation is important in tissue repair. Subsequently, how the effect affects stem cell therapy is also the direction we will continue to explore. Luo Zhiqiang said.
Resources:
1.Ping Chen et al. ACS Nano 16, 10, 16513–16528(2022). https://doi.org/10.1021/acsnano.2c05818
2.Ping Wu et al. Nano Energy 102, 107707（2022）. https://doi.org/10.1016/j.nanoen.2022.107707
3.Ping Chen et al. Nano Energy 86 ，106123（2021）. https://doi.org/10.1016/j.nanoen.2021.106123