Accelerating Bone Formation Inspired by Nature

Research by Iranian scientists in regenerative medicine shows that engineered scaffolds mimicking both the structure of bone cells and the piezoelectric properties of bone can direct stem cells toward forming bone tissue using only physical stimuli, speeding up the bone-building process.

Ambassador of Arjan-Social Group: Fateme Poladzadeh, PhD student of this university, with the guidance of Dr. Ali Asghar Katbab and Shadab Bagheri, one of the faculty members of the university, and with the cooperation of Shahin Bankdar, a member of the faculty of the Pasteur Institute of Iran, a research project entitled "Design and construction of a patterned substrate containing piezoelectric behavior with the ability to differentiate stem cells into osteoblast cells based on performed PVDF/PDMS/BaTiO3”.

Recalling that research has been carried out in the field of bone tissue engineering and regenerative medicine, Poladzadeh said: This field has become one of the most important research fields in the world in recent years, because with the increase in bone injuries caused by accidents, diseases and aging, the need for new methods to repair and regenerate bone tissue is felt more than in the past.

Referring to the special attention of researchers to the use of stem cells for the treatment and regeneration of damaged tissues in recent years, he stated: Nevertheless, the effective guidance of these cells towards the formation of bone tissue is still one of the main challenges in this field. Therefore, the aim of this research was to design a smart platform inspired by the biological properties of bone tissue to direct stem cells to the formation of bone tissue without using chemical agents and only by simulating the physical characteristics of natural bone tissue.

This student of Amirkabir University of Technology continued: To achieve this goal, two important features of bone tissue were reconstructed simultaneously; First, the specific structure and pattern of bone-forming cells, and second, the natural piezoelectric property of bone, which is created in response to mechanical forces in the body. It was expected that the combination of these two factors could create an environment closer to the natural conditions of the body and accelerate the bone formation process.

This researcher said about the results of this research project: The results showed that the designed substrates were able to effectively accelerate the bone differentiation process of stem cells without using chemical agents and only by using physical stimuli. The stem cells cultured on these substrates had favorable growth and survival and turned into osteogenic cells at a faster rate.

This researcher of Amirkabir University of Technology emphasized: Cell and molecular studies showed that the main markers of bone formation were activated in a short period of time, and the initial signs of bone tissue formation were observed only after seven days. These findings indicate the high ability of the designed substrates in creating an environment similar to the natural bone tissue and accelerating the bone formation process.

Stating that the importance of this achievement lies in the simultaneous use of two key physical factors, Poladzadeh stated: In this system, for the first time, the synergistic effect of the specific topography of bone cells and piezoelectric properties has been used to guide stem cells. This technology can lay the foundation for the development of safer, less expensive and closer to the natural conditions of the body in the field of regenerative medicine.

He stated that this research started with the extraction of bone cells or osteoblasts from the natural bone tissue, and reminded that: after separating the cells, their surface structure was patterned by the cell molding method so that the topography of the plasma membrane of the bone-forming cells could be accurately reconstructed on the engineered substrates.

Poladzadeh continued: The research was done in two separate stages. In the first stage, the performance of polydimethylsiloxane (PDMS) substrates containing barium titanate (BaTiO3) nanoparticles was investigated in vitro, and in the second stage, PDMS substrates containing electrospun polyvinylidene fluoride (PVDF) nanofibers and PVDF/BaTiO3 nanofibers were evaluated. The purpose of designing this system was to reconstruct the surface topography properties and the electromechanical behavior of the natural bone tissue at the same time.

He said: After making the substrates, their effectiveness in inducing bone differentiation of stem cells was checked. At this stage, the stem cells extracted from fat tissue were cultured on the substrates and by applying mechanical strains in the physiological range, the growth rate, viability and bone differentiation of the cells were measured through biological tests and using quantitative and qualitative evaluations.

Poladzadeh named the uniform dispersion of barium titanate nanoparticles in the PDMS substrate as well as the proper distribution of PVDF nanofibers in this system as the most important challenges of the project and added: extraction of human cells from natural tissues, coordination with medical centers, long-term cell culture and control of possible contamination were also sensitive and time-consuming parts of this research.

He explained about the applications of the results of this research project: the achievements of this research can be used in the field of bone tissue engineering, regenerative medicine, cell therapy and the development of smart biomaterials. This technology can be used in the future to produce bone cells needed in the treatment of complex fractures, bone defects and injuries caused by diseases.

Poladzadeh pointed out that this achievement can also be used in the design of advanced tissue engineering scaffolds, bioactive implants and the production of knowledge-based products related to regenerative medicine.

About the publication of the results of this research, he said: Part of the results of this project, which is dedicated to the design and evaluation of molded substrates containing barium titanate nanoparticles, has been published in the form of a scientific article in the Journal of Materials Chemistry B.

This student of Amirkabir University of Technology considered the main innovation of this article to be the simultaneous use of two important physical factors including the specific topography of bone cells and piezoelectric properties in a single system and noted: The results showed that the synergistic effect of these two factors can create conditions close to the natural bone environment without the need for chemical agents and accelerate the bone formation process. The second part of this research, based on the use of PVDF nanofibers containing barium titanate, is being prepared for publication in scientific journals.

He mentioned the next step of this research is conducting in vivo studies and animal tests and said: At this stage, the differentiated cells can be placed on biodegradable scaffolds and implanted at the site of bone damage or directly injected into the site of damage so that the amount of tissue regeneration can be evaluated in real body conditions. The implementation of this step can pave the way for technology to enter therapeutic and industrial applications.

Poladzadeh explained that smart piezoelectric materials were used in this research along with cell molding technology to create an environment close to the actual conditions of the body, and continued: Unlike many common methods, this method does not depend on chemical agents to induce cell differentiation and uses physical stimuli inspired by nature.

He stated that the most important competitive advantage of this technology is directing stem cells towards bone formation without the need for chemical agents, and he noted: In addition to reducing costs, this feature can increase the safety and stability of the production process of therapeutic cells. Designed substrates are reusable and can be used for a long time in cell culture processes. By reducing the need for long-term cell passages, this method prevents the change of phenotype and loss of quality of cells, and as a result, the produced cells will be more suitable for therapeutic applications.

According to this researcher, this achievement can be used in the development of new methods of cell therapy, the production of bone cells to repair bone lesions, the construction of smart tissue engineering substrates, the development of bioactive implants, and the advancement of regenerative medicine technologies.