The main objective of our group is to investigate and develop methods, procedures, and technologies which are applicable to basic and clinical medicines as well as basic research of biology and medicine from the viewpoint of material sciences. In our group, various types of biodegradable and non-biodegradable biomaterials of polymers, metals, ceramics, and their composites, are being designed and created aiming at their clinical applications as well as the development of experimental tools necessary for basic research of medicine and biology which scientifically support clinical medicine.

We are actively proceeding research and development (R & D) of biomaterials to assist reconstructive surgery and apply to drug delivery systems (DDS) for improved therapeutic efficacy. However, it is often difficult for patients to improve their Quality of Life (QOL) only by the therapeutic procedure of reconstructive surgery because the biomaterials applied are of poor biocompatibility and functional substitutability. For organ transplantation, there are several problems to be resolved, such as the lack of donor tissue and organ or the adverse effects of immunosuppressive agents. The two advanced medical therapies currently available are clinically limited in terms of the therapeutic procedure and potential.

Our research group is actively performing to promote various basic research and application of biomaterials to "cell biotechnology". Biomaterials are materials (polymers, metals, ceramics, and their complexes) that are used in the body or in contact with cells and body components (such as proteins, nucleic acids, polysaccharides, or lipids), bacteria, and viruses. The research area is not limited to artificial organs (medical devices) and drug delivery systems (DDS) that everyone Mr./Ms. imagines. Biomaterials provide important technologies and methodologies to support regenerative therapies, cell culture, and drug discovery screening. In cell research, drug discovery research, clothing, cosmetics, healthcare, and health foods, materials that come into contact with cells and biological components are required, and this is where biomaterials come into play.

Biomaterials are one of the indispensable items for the realization of the field of life sciences (translated as life sciences in universities and life sciences in society). In the past, "biotechnology" was researched on proteins, genes, bacteria, and viruses, but now its target has expanded to include cells. There is no doubt that biomaterials will occupy an important position in this field of "cell biotechnology" in the future. In our research group, we are promoting research and development in the field of "cell biotechnology" from the perspective of biomaterials through functional connections between industry, academia, and government.

The term "regenerative medicine" is now widely known to the general public. However, the way of thinking and perceiving it varies from person to person.

So, what is "regenerative medicine"? Here, we can classify " regenerative medicine " into "therapy" and "research" (supporting future therapy. The general image of regenerative therapy is to treat diseases by the proliferation and differentiation ability of cells transplanted in the body. This is not always a mistake. The essence of regenerative medicine is to enhance the patient's own natural healing power and treat the disease. Of course, the foundation of natural healing power is the ability of cells, and there is no doubt that cells are important. The best medical treatment for a cold is to get nourished and get a good night's sleep. For example, it is unlikely that anyone will receive a cell transplant to treat the common cold. This is because if the cellular ability in the body can be restored and the natural healing power can be enhanced, the disease will be cured naturally. In other words, regenerative therapy is also possible by enhancing the ability of cells that originally exist in the body and rejuvenating the cells. Specifically, it is to give the cells a good local environment and energize the cells. The in vivo local environment of cells consists of an extracellular matrix (the house of the cell) and humoral signaling factors (the food/drink of the cell).

If we can prepare a home out of the materials that the cells like and provide them with their food/drink using drug delivery system (DDS) technology, the cells in the body will be energized where they are needed, and we will be able to treat diseases. In addition, regenerative therapy can be realized by rejuvenating cells in the body by various methods, such as increasing the viability of transplanted cells in the body by improving cell habitat and nutrition, moving cells to necessary sites, and controlling the inflammatory response in the surrounding environment. These sets of materials, techniques, and methodologies are also useful for "research". Three-dimensional cell culture materials, technologies, and methodologies such as cell sheet stacking and cell aggregates have been researched and developed. Culturing cells under three-dimensional conditions that are close to the in vivo local cell environment, genetically modifying cell functions, and producing organoids will bring innovation to cell research and drug discovery research. Regenerative medicine will be further developed by integrating engineering and pharmaceutical technologies for creating cells and their local environment, and bridging the gap to commercialization.

There are four areas of regenerative medicine. 1) cell transplantation, 2) tissue engineering, 3) drug discovery research, and 4) gene therapy.

No 1), 2), and 4) are "therapy", and 2), 3), and 4) are "research", but it can be seen that the key is to "energize cells" in all fields. Regarding 1), the target cells include not only stem cells, but also cancer immunotherapy such as CAR-T cells. If the cells are healthy, the therapeutic effect will be enhanced. 2) is the creation of an environment around cells using material technology. If this is done inside the body, it will be "treatment", and if it is done outside the body, the efficiency of "research" will increase. Drug screening using three-dimensional culture technology corresponds to 3). We use cells in a three-dimensional environment close to the inside of the body to evaluate drug efficacy, metabolism, toxicity, etc., and develop new drugs. 4) is centered on the modification and regulation of cellular functions at the genetic level. Internationally, all four of these areas are similarly considered to be indispensable areas of regenerative medicine. What about Japan? In the field of regenerative medicine, it is important to recognize that the target cells and related technologies are now expanding significantly. "Regenerative therapy" requires obtaining permission from the Ministry of Health, Labor and Welfare, and it takes money and time to put it into practical use. On the other hand, in cell research and drug discovery research, any material or technology can be used as long as all cells do not die, and the hurdles for commercialization are lower than the former. When aiming for commercialization, it is necessary to have a good understanding of the difference between exits to the regenerative medicine industry.

So far, from the standpoint of biomaterials, we have looked at "regenerative medicine" in the area of interdisciplinary medicine and engineering. At this point, it would be interesting to review this area from a different perspective. "Biotechnology" is a research field that has been developed in the field of fusion of biomedicine and science and engineering. The target subjects of this research are proteins, genes, bacteria, etc., and various commercializations have already been realized based on the results of the research. How about thinking that "cells" have been newly added to the target subject? We will direct the materials, tools, and technologies that have been obtained so far to the "cells" and make the most of the functions of the cells (energize the cells). This is the essence of regenerative medicine, and regenerative medicine is considered to be "cell biotechnology." Based on this idea, it is necessary to have some kind of mechanism that "crosses" the many fields of research, from basic research and applied research to its commercialization. This research group is expanding the circle of academia beyond fields and promoting functional connections between industry, academia, and government for the further development of regenerative medicine (regenerative therapy + regenerative research). Representative research topics are described below.

We are designing and creating 3-dimensional and porous constructs of biodegradability as cell scaffolds of an artificial ECM which supply the local environment of cells proliferation and differentiation. As another technology to promote the proliferation and differentiation of cells, the biodegradable carriers for the controlled release of growth factors and genes are being designed and prepared from gelatin and its derivatives. A new therapy to naturally induce tissue and organ regeneration by the controlled release of various biologically active growth factors has been achieved, and the therapeutic potentials have been scientifically demonstrated through animal experiments. Among the tissue regeneration trials, clinical experiments of angiogenic and bone regeneration therapies have been started by the controlled release technology of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) -1, and platelet-rich plasma (PRP) to demonstrate the good therapeutic efficacy. In addition, the systems of drug targeting and the local release with polymers of an organ affinity are being designed and prepared to achieve the regeneration therapy for chronic disease based on the natural healing potential of patients.

The technology and methodology of cell culture with various biomaterials and bioreactors have been explored to efficiently isolate, proliferate, and differentiate stem cells, precursors, and blastic cells. A series of this study not only aims at the preparation of cells suitable for the therapy of regenerative medicine, but also research and development (R&D) of materials, technologies, and methodologies for basic medicine and biology. They are also applicable for the research of drugs discovery to evaluate their metabolism and toxicity. In addition, non-viral vectors for low-molecular weight compounds, peptides, proteins, and nucleic acids (siRNA and decoy DNA) have been investigated to design the DDS system for gene transfection which can biologically analyze the functions of stem cells and genetically engineer cells to activate the biological functions for cell therapy.

The minimum unit of body is cell, but that of biological function is the cell aggregate. The cell culture with cell aggregates has been noted for the basic biological and medical research of cells and drug discovery (the drug development and the toxicity evaluation). However when the size of cell aggregates becomes larger, the cells in the aggregates tend to die because of the lack of nutrients and oxygen. As one trial to break through the problem, microspheres incorporation enabled cells to improve their function even in the cell aggregate.

Generally, there are few drugs which have a specific selectivity for the site of action. Therefore, the high- dose administration of drugs is necessary to achieve their in vivo therapeutic efficacy, while this often causes the adverse effects of drugs. DDS is a biomaterial-technology which allows a drug to act at the right time the right site of action at the necessary concentration. The objective of DDS includes the controlled release of drug, the prolongation of drug life-time, the acceleration of drug permeation and absorption, and the drug targeting. Various biomaterials are inevitably required to achieve every DDS objective. The drugs applicable for DDS include therapeutic drug and gene, diagnostic and preventive drugs, cosmetics, or health care substances etc. The basic idea of DDS is to efficiently enhance the biological functions of such drugs by their combination with biomaterials. Other than the therapeutic drug and gene, the DDS technology and methodology can be applied to enhance the in vivo efficacy of vaccination and diagnosis, such as magnetic resonance imaging (MRI), ultrasound diagnosis or molecular imaging. In addition, we are investigating DDS technology and methodology which are applicable to the research and development of cosmetics and health care sciences.

We molecularly design and creates biomaterials and the related technology mainly from biodegradable polymers aiming at the development of assistant materials and medical devices in surgical and physical therapies.