Journal of Simulation and Analysis of Novel Technologies in Mechanical Engineering 

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Feasibility study of mechanical properties of alginates for  neuroscience application using finite element method

Maryam Karimianmanesh1, Elham Azizifard2, Naghmeh Javidanbashiz2, 

Mehran Latifi1*, Atefeh Ghorbani3, Sheyda Shahriari4 

1Department of Mechanical Engineering, Najafabad Branch, Islamic Azad University, Isfahan, 8514-3131, Iran 2Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran

Biotechnology Department., Falavarjan Branch, Islamic Azad University, Isfahan, Iran 

4Institute of Psychiatry, Psychiatry and Neuroscience, Kings College London, London, UK   

(Manuscript Received — 02 Feb. 2022; Revised — 24 Mar. 2022; Accepted — 26 Mar. 2022) 


Alginate is a natural polysaccharide that is extracted from alga sources mainly laminaria. Alginate is  readily processable for applicable three-dimensional (3D) scaffold materials such as hydrogels,  microspheres, microcapsules, sponges, foams and fibers. Alginate hydrogels have been particularly  attractive in wound healing, drug delivery, neuroscience and soft tissue engineering applications. As  these gels retain structural similarity to the extracellular matrices (ECM) in tissues and can be  manipulated to play several critical roles. The nervous system is a crucial component of the body and  damages to this system, either by of injury or disease which can result in serious or potentially lethal  consequences. In this research, the aim is to simulate nerve fibers in Abaqus simulation software by  finite element method (FEM). Also, the use of a similar material such as alginate can be used to  validate this simulation. Restoring the damaged nervous system is a great challenge due to the  complex physiology system and limited regenerative capacity. Currently, most of neural tissue  engineering applications are in pre-clinical study, in particular for use in the central nervous system,  however collagen polymer conduits aimed at regeneration of peripheral nerves have already been  successfully tested in clinical trials. In this study, due to the complexity of measuring nerve endurance,  static simulation was used in Abaqus software and the results showed that paired strings are stronger  than the number of individuals and the string plays a key role in the center. 

Keywords: Biocompatible materials, Hydrogel, Tissue engineering, Nerve regeneration 

1- Introduction

Alginate is a group of compounds that are generally considered safe by the Food and  Drug Administration (FDA). The  mechanical properties of alginate  hydrogels are determined by the sequence  and composition of its constituent  monomer chains [1-3]. Alginate is used as  the salt of sodium, and due to the addition  of salts of divalent cations such as calcium and barium, etc., and special trivalent cations such as iron and aluminum, which  cause ionic bonding and crosslinking of  carboxyl groups of polymer chains [4-7] the mechanical strength of alginate  hydrogels depends on the tendency of the cations to alginate. Studies have shown  that the chemical structure, molecular size  and process of hydrogel gel formation play  an important role in its properties such as  swelling, stability, biodegradability, safety and biocompatibility properties [8-14].  Large proteins such as fibrinogen can  easily pass-through calcium alginate  hydrogels. Only cells and some high  molecular weight enzymes such as catalase  remain completely in the alginate hydrogel [15-21]. Alginate is biocompatible and  harmless to the body and is used in the  food industry as a thickener and stabilizer. This biocompatible hydrogel has been  considered today due to its ease of  preparation and its suitable properties for  encapsulating cells. The alginate scaffold  is formed by the cross-linking of calcium  cations and can be degraded by the  removal of calcium [22-28]. Alginate  lattice congestion in hydrogels is related to  the hardness of the alginate, which is  directly affected by the cation concentration. The results of studies have  shown that increasing the hardness of the  hydrogel leads to a decrease in the  permeability of the hydrogel and  consequently a decrease in the viability  and proliferation of encapsulated nerve  stem cells [29-36]. It is used in the food,  cosmetics and pharmaceutical industries  [37-45]. The beneficial properties of  alginate, such as biocompatibility and non stimulation of the immune system, are  probably related to its hydrophilic  properties [46-51]. As cells are not  damaged during the gel formation and ion  crosslinking process, it is widely used to release drugs, encapsulate cells, and  regenerate tissue [52-55]. Extracellular  matrix (ECM) polysaccharides affect  axonal conduction, function, synaptic  evolution, and cell migration [56].  Therefore, polysaccharide scaffolds and polysaccharide-modified scaffolds, such as  alginate, are crucial to the development of  neural tissue engineering. Alginate  polysaccharide sequences can act as  functional groups in the ECM of the brain,  which can modulate signal transduction  pathways to guide cell migration and nerve  growth. Alginate has been used to fill  cavities in brain and spinal cord injuries in  mice. It has also been used to stop  astrogliosis in damaged central nervous  system areas [54-55]. In this study, the aim  was to predict the properties of neural  neurons with the supports of Abaqus  software and finite elements analysis  (FEA) according to the existing variables  worked for polymer alginate.

2- Physical characteristics  

Many scaffolds used in soft tissue  engineering generally fill the space  normally occupied by the host tissue and  act as a framework for the cells that will  repair the lesion in the future. In addition  to being able to withstand the load that  enters the tissue naturally, the graft also  needs to be able to provide the strength  needed for the growth of cells on the  scaffold [58-62]. Alginate ion bonds have a  stronger mechanical strength when they are  formed by adding divalent cations with a  higher affinity for the polymer. The presence of these variables in the  biomechanics of the scaffold makes it  possible to create a suitable ECM for each  tissue in accordance with the physiological  characteristics of the tissue in question [62- 64]. In most cases, cells cannot attach to  hydrogels because they lack receptors, except for collagen, which is one of the  proteins that make up the extracellular matrix. Because hydrogels are hydrophilic,   ECM proteins cannot readily be absorbed on their surfaces [13]. The best way to modify hydrogel levels to provide cell binding receptors is to bind an ECM protein or a peptide sequence by covalent bonding to the hydrogel surface [14]. For this purpose, peptide sequences are mainly used. This sequence is naturally present in ECM proteins such as laminin, fibronectin and collagen. Numerous studies have been performed to prove that the peptide mentioned above can bind to alginate by  covalent bonding, and it has been shown to improve the attachment of nerve cells [15- 18]. Studies have shown that YIGSR and  IKVAV sequences promote a greater  number of neurites in each neuron as well  as selective binding of neurons [16-21].

3- Mechanical simulation of central  nervous system in the FEM

Alginate has been studied as a degradable scaffold in vitro and in vivo to guide nerve fibers [17]. The study showed that the arrangement of axons relative to each other in alginate scaffold after transplantation in the spinal cord injury area was parallel t0 the control group, while in the axon control group neurons grew in different directions.  Therefore, the use of alginate can manage the major challenge of directing axon regeneration throughout the lesion site. But an important issue to consider when using alginate as a scaffold to repair nerve damage is the high rate of degradation of the substance in the body and it decomposes before axons can grow more than 2 mm at the site of the lesion [18].

Fig. 1 Investigation of elastic properties of  polymeric nerve fibers 

Therefore, in order to use an alginate  scaffold to repair nerve damage, a method  should be used to reduce its degradation  rate. Several researchers model becomes  spinal cord injury [19-26]. Researchers showed the injection of this scaffold in a  mouse. The model of spinal cord. Hemi  section produces more neurofilament in the  lesion region, On the other hand, another  study showed that alginate may provide a  suitable environment for increasing the  length of spinal cord axons [25-36]. In one  study, an alginate scaffold with a spongy  structure was used, and nerve stem cells were isolated from the hippocampus and  injected after culture, and finally the  composite structure was transplanted to the  injury site [52-54]. The obtained their  results of the study showed that the motor  symptoms improved, and the injured area  was repaired histologically. Mesenchymal  stromal cells (MSCs) have been shown to  regulate the inflammatory environment of  various tissues in the body, including the  central nervous system. Until now,  however, the success of direct use of these  cells in the brain has been limited due to  the depletion of these cells. In this study,  the TET structure with the boundary conditions of the two closed sides was used  and a force of 100 N was used.

Fig. 2 Investigation of Von Mises Stress (VMS) of  simulated nerve fibers in Abaqus software with a  force of 100 N 
Fig. 3 Myelin formation in the nervous system  begins from the embryonic period until puberty [26] 

In the study of finite elements analysis, it  can be found that most of the stress  concentration occurs in the center. It is also  shown in Fig. 1(d) that a single string in  the center and on the edges contains the most stress. Fig. 2 (a-d) shows the surface  of the filaments with 20 strands and the  cross section of the cross-section, while the  stress level boundary shown in Fig. 2 under load shows well that the fibers in the  center withstand the highest stresses. In  neuroscience, the methods of  neuroimaging, computed tomography  (CT), positron emission tomography  (PET), operative magnetic resonance  imaging (FMRI), and the study of the  inside of the brain. The application of  artificial intelligence and machine learning  in biological data and neural imagery  opens new frontiers for bioinformatics: Increasing the understanding of the  umbilical cord. Advances in this field can  eventually lead to the development of  automated diagnostic tools as well as the  precise medicine that may be taken into  consideration by considering a specific  treatment method. Prior to the advent of  machine learning algorithms,  bioinformatics algorithms had to be  handwritten to solve problems such as  predicting protein structure. The obtained  results of this study show that the stem  cells encapsulated in alginate have the  ability to be used as an improved carrier  for transplantation and also this method  has a therapeutic effect on inflammation of  the nervous system [21-36]. Transplantation of encapsulated  mesenchymal stem cells with alginate  improves cellular pathology after brain  injury [22-24]. Razavi et al. [37] studied  the safety, regulatory issues, long-term  biotoxicity, and the processing environment of hydrogels. Fig. 3 shows the  myelin formation in the nervous system  begins from the embryonic period until  puberty.


The use of a similar material such as alginate  can be used to validate for this simulation. Restoring the damaged nervous system is a  great challenge due to the complex physiology system and limited regenerative capacity.  Currently, most of neural tissue engineering  applications are in pre-clinical study, in  particular for use in the central nervous system,  however collagen polymer conduits aimed at  regeneration of peripheral nerves have already  been successfully tested in clinical trials. This  material can be used in many medical  applications, especially in the fields of  wound healing, drug transfer, cell culture  in vitro and tissue engineering. Alginate  has effective properties such as  biocompatibility, cheapness and  availability of raw material and the  possibility of applying simple changes to  prepare alginate derivatives with new  properties. Mammalian cells do not have  receptors for alginate polymers, which  make alginate gels relatively ineffective.  One way to create cell adhesion is to use  cell adhesion molecules such as laminin, fibronectin, and collagen with alginate. Alginate decomposition can be controlled  by manipulating its molecular weight and  composition. According to the strategy of  using molecules with different chemical  structure, different molecular weights, it is  possible to design and fabricate alginate  scaffolds suitable for use in various tissues,  including nerve tissue. Alginate scaffold  can play an important role in neural tissue  engineering as it maintains a structural  similarity to the ECM in tissues. However,  the use of this hydrogel as a cell scaffold in  vivo in humans requires further studies. n  this study, due to the complexity of measuring  nerve endurance, static simulation was used in  Abaqus software and the results showed that  paired strings are stronger than the number of  individuals and the string plays a key role in  the center. 


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