According to relevant data in 2019, there are 270,000 spinal cord injury patients in the United States. The epidemiological statistics of spinal cord injury in my country are relatively discrete, and it is estimated that there are about 2 million SCI patients. The team of Zhang Zhijun, a researcher at Suzhou Institute of Nanotechnology and Nanobionics, Chinese Academy of Sciences, has developed a new conductive neural scaffold, providing a new strategy for the repair of SCI.
Spinal cord injury (SCI) is a common traumatic disease that often occurs in people under the age of 30. This disease can cause the interruption of the neural connection between the brain and surrounding organs , thereby causing the loss of sensory and motor functions below the damaged segment, and even causing complications such as respiratory infection , urogenital system infection, bedsores and other complications.
According to relevant data in 2019, there are 270,000 spinal cord injury patients in the United States, and the annual treatment costs exceed US$6 billion. The epidemiological statistics of spinal cord injury in my country are relatively discrete, and it is estimated that SCI patients are about 32 million of them in htmlhtml. The painful and long recovery process and expensive treatment costs have put serious burdens on SCI patients and their families.
researchers used extruded biological 3D printing to prepare loaded neural stem cell (NSC) scaffolds, which promoted the repair of spinal cord injury to a certain extent. However, this bionic scaffold is still mainly composed of the parallel arrangement structure of , which simulates the spinal cord nerve tract. It lacks bionic , which has electrophysiological functions of spinal cord tissue, and it is difficult to meet the requirements of spinal cord electrical signaling.
In response to the above challenges, Zhang Zhijun, a researcher team from the Suzhou Institute of Nanotechnology and Nanobionics of the Chinese Academy of Sciences, developed a new conductive neural scaffold based on methacrylated gelatin (GelMA), methacrylated hyaluronic acid (HAMA) and poly(3,4-ethylenedioxythiophene):sulfonated lignin (PEDOTh:LS), providing a new strategy for the repair of SCI. Related research results are published on Chemical Engineering Journal, Zhang Zhijun, researcher at the Suzhou Institute of Nanometer, Chinese Academy of Sciences, and Huang Jie, associate researcher, are the corresponding authors of . What theoretical basis is this new conductive neural scaffold based on? What technical means were used? What application prospects are there? " Science and Technology Guide " interviewed Huang Jie, associate researcher at the Suzhou Institute of Nanometer, Chinese Academy of Sciences.
Figure 1 Schematic diagram of 3D bioprinted conductive neural scaffolds promoting the differentiation of neural stem cells into neurons and repairing spinal cord injury (Source: Chemical Engineering Journal)
Please briefly introduce the scientific research results of biological 3D printing conductive neural scaffolds? What core problems has it overcome?
Huang Jie: Spinal cord injury is a serious traumatic disease of the central nervous system. It is clinically manifested as temporary or permanent loss of local or even all limb sensation and motor function below the injury level. It will not only cause serious physical and psychological damage to the patient, but also cause a huge economic burden to the entire society. Its treatment and rehabilitation have become a major problem in the medical field at present. In recent years, the construction of bionic scaffolds using biological 3D printing technology has provided new strategies for spinal cord injury repair. However, the currently developed bionic scaffold is still mainly used to simulate the spinal cord structure. lacks bionic to the electrophysiological function of spinal cord tissue, and it is difficult to meet the requirements of spinal cord nerve electrical signaling .
In response to the above challenges, this study developed a novel conductive neural scaffold based on methacrylated gelatin (GelMA), methacrylated hyaluronic acid (HAMA) and poly(3,4-ethylenedioxythiophene):sulfonated lignin (PEDOT:LS).Among them, GelMA/HAMA simulates nervous system extracellular matrix , providing mechanical support for scaffolds and providing a suitable growth environment for neural stem cells; the introduction of PEDOT:LS significantly improves the conductivity of scaffolds, achieving conductivity (0.60 S m-1) comparable to natural spinal cord white matter. By precisely adjusting the photocuring time, this scaffold exhibits similar mechanical properties to spinal cord tissue (energy storage modulus ≈1 KPa), and its porous structure and swelling properties are suitable for the growth of neural stem cells. The precursor solution was blended with neural stem cells to prepare bioink, and the conductive neural scaffold was prepared by extruded biological 3D printing technology. After
printing, the survival rate of neural stem cells exceeded 90%, and showed good proliferation behavior in the scaffold. Compared with non-conductive neural scaffolds, conductive neural scaffolds significantly promote the differentiation of neural stem cells into neurons. On this basis, a total transverse injury model of spinal cord in rats was constructed. The implanted conductive nerve stent greatly promoted the regeneration of neurons at the injury site, reduced the deposition of glial scars, and promoted the regeneration and myelination of nerve axons, effectively improving the motor function of hind limbs of rats with spinal cord injury. What was the original intention of the
team to carry out this research? How long did this study take to be completed?
Huang Jie: Spinal cord injury repair has always been a world problem, mainly because neurons after injury cannot be regenerated. In response to this problem, our team has used biological 3D printing technology to build a series of bionic scaffolds since 2017 and promote the regeneration of neurons at the damage by loading neural stem cells. In the study, we found that the conduction of electrical signals plays a very important role in promoting the regeneration of neurons. To this end, we constructed a neural scaffold that mimics the spinal cord structure to simulate the electrical conduction characteristics of spinal cord tissue, further improving the repair effect of the scaffold. This study took 2 years to complete .
At this stage, what are the ways to treat spinal cord injuries in clinical practice?
Huang Jie: Currently, the main ways to treat spinal cord injuries in clinical practice are surgery, medication and rehabilitation treatment. surgical treatment mainly performs internal and external decompression and internal fixation, stabilizes the spine, prevents further aggravation of damage, and creates good conditions for spinal cord recovery. Drug treatment main purpose is to improve the microenvironment of the damaged site, including inhibiting inflammation and edema , and play a role in protecting nerve cells. The drugs that are currently used are: sodium methylprednisolone succinate, ganglioside, etc. Rehabilitation treatment mainly restores the patient's muscle strength, self-care ability, etc. through rehabilitation training, including exercise training, electrical stimulation treatment, weight loss gait training, acupuncture and psychological intervention.
Can these measures effectively restore patients' sensory and motor functions?
Huang Jie: Whether can restore the patient's sensory and motor function depends on the type and degree of the injury . Severe spinal cord injury will cause lifelong paralysis and it is difficult to recover; minor injuries can restore part of the perception and motor function when properly treated.
The rapid development of tissue engineering technology provides a new strategy for SCI repair. When can the development of this bionic scaffold be traced back to?
Huang Jie: The concept of tissue engineering was proposed in 1987. Shortly after that, scientists used directional arrangement of carbon filaments to induce the directional growth of nerve cells to treat spinal cord injury rats. 2000 , tissue engineering technology has been widely used in the research on spinal cord injury repair.
As of now, how many types have been developed?
Huang Jie: At present, neural scaffolds can be divided into several categories according to their function: neural scaffolds that provide mechanical support for damaged tissues, neural scaffolds that induce directional growth of endogenous cells, neural scaffolds that load exogenous neural stem cells to replace necrotic nerve cells, neural scaffolds that load neural factors and drugs to promote the growth of cells neural scaffolds that improve the microenvironment of the damaged site, neural scaffolds that promote electrical signaling, neural scaffolds that promote vascular ization of the damaged site, etc. How many types of bionic neural scaffolds have been invested in clinical treatment at present?
Huang Jie: At present, there are more than ten clinical trials in the world, such as NeuroRegenScaffoldTM developed by the team of Dai Jianwu researcher researchers. Their clinical experimental results show that implanting a stent will not cause adverse symptoms to the human body and will have a certain effect on the recovery of sensory function. What are the biggest advantages of the biological 3D-printed conductive neural scaffold developed by the team this time compared with other scaffolds based on traditional tissue engineering methods?
Huang Jie: Natural spinal cord tissue has a certain spatial order in its appearance structure and cell distribution, and there is electrical signal transmission between neurons. Compared with traditional tissue engineering scaffolds, the biological 3D printed conductive neural scaffold we developed this time can accurately control the spatial arrangement of cells and materials on the one hand, and simulate the bionic three-dimensional structure of the spinal cord. On the other hand, can restore the conduction of spinal cord electrical nerve signals . The two combined induce the differentiation of neurons at the injury to improve the therapeutic effect of spinal cord injury rats.
Figure 2 Motor function recovery in SCI rats after treatment with conductive neural scaffolds. Figure A is the BBB score; Figure B is the slope test results of SCI rats at 8 weeks postoperatively; Figure C is the hind limb extension status of SCI rats at 8 weeks postoperatively. (Source: Chemical Engineering Journal)
What are the advantages and disadvantages of the new generation of scaffolds based on new conductive hydrogels compared with the team's previously produced scaffolds with loaded neural stem cells (NSCs) using extruded biological 3D printing?
Huang Jie: Compared with the scaffolds developed previously, the main advantage of the conductive neural scaffold developed this time is that gives the scaffold the conductivity matching the spinal cord tissue . The conductive scaffold is conducive to the recovery of nerve electrical signaling function, which can further promote the differentiation of neural stem cells into neurons. The main disadvantage is that the conductive neural scaffold is cured by photocrosslinking, and blue light exposure may have a certain impact on the vitality of neural stem cells.
Do you think there is still something worth optimizing for this R&D result?
Huang Jie: In the construction of scaffolding, you can consider developing Multifunctional biological 3D printing scaffolding , for example, loading a variety of drugs and neural factors to promote the repair of spinal cord injury. In addition, the mechanism of action of spinal cord injury repair can also be explored in depth, such as the conduction mechanism of conductive neural stents to electrical nerve signals.
Did the team go through some difficulties during the research process? And how to overcome it?
Huang Jie: Neural stem cells are extremely sensitive and fragile cells, so they put high requirements for the design of materials and the printing process of scaffolds. The design of conductive neural scaffolds should take into account multiple functions. : it has mechanical strength and conductivity that matches spinal cord tissue; porous structure is suitable for neural stem cell growth; good biocompatibility , degradability, printability, etc.It also meets the conditions such as the scaffolding is stable and does not collapse during printing and the high cell survival rate after printing.
In the entire research process, we also explored a little bit, combined with the foundation of the previous work, on the one hand, finds inspiration from existing research , and on the other hand, continues to try , optimize the types and ratios of materials, explore printing parameters, conditions, etc., and find solutions to problems in practice.
Can you talk about the application prospects of this biological 3D printing conductive neural scaffold? When is it expected to be applied to clinical treatment on a large scale?
Huang Jie: In this study, SD rat was used as an animal model, and good treatment results were achieved. However, before clinical treatment, more large animals need to be selected, such as beagle , monkeys, etc., for experiments to verify their safety and effectiveness.
Spinal cord injury repair is a global medical problem. It requires a large number of scientific research teams, medical institutions, medical management departments, etc. to cooperate to promote a new treatment method to the clinic. This technology will take a long way to go for large-scale clinical treatment.
Figure 3 Conductive neural scaffold implantation promotes myelin regeneration (immunofluorescent staining diagram of longitudinal sections of spinal cord) Immunofluorescent staining of Olig2 (A) and MBP (B) and quantitative analysis of Olig2 (C) and MBP (D). (Source: Chemical Engineering Journal)
What do you think are the problems that hinder the promotion and application of this achievement at this stage?
Huang Jie: The main problems that hinder the promotion and application of this result at this stage include: 1. The long-term safety and stability of the scaffold in large animals, which also require long-term research and a large number of experiments to support; 2. The mechanism of the conductive scaffold in the body of nerve signaling is not clear, and in-depth research is still needed.
Can you talk about the team’s next stage of research plan and goals?
Huang Jie: The next stage of the research work of the team will be carried out from three aspects: 1. Research on the safety and effectiveness of stents in large animals; 2. Research on the repair of other electroactive tissues, such as the brain, peripheral nerves, myocardium, skin, etc.; 3. Further research on the mechanism of action of conductive stents in the body.
Huang Jie, associate researcher at the Suzhou Institute of Nanotechnology, Chinese Academy of Sciences, and deputy director of the Department of Nanobiology. Graduated from , Department of Materials and Chemistry and Chemical Engineering, Soochow University, , and a doctoral student. In recent years, it has been mainly engaged in the development of new polymer hydrogels and its application in stem cell regenerative medicine; the design and synthesis of various nanomaterials, and its application in stem cell tracer and tumor imaging. As the first author or corresponding author, he has published more than 20 papers in journals such as Advanced Materials, Advanced Functional Materials, Biomaterials, Small and other journals.
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