The mission of this lab is to develop innovative medical technologies based on the science of biomaterials, DDS, and molecular biology. We aim at regulating biofunctions of host cells and the biomaterials, obtaining proof-of-concept of the therapeutic strategies by animal studies, and pursuing their clinical applications in collaboration with hospitals and companies.

1.mRNA-based therapeutics: a new paradigm of gene therapy
Gene therapy is defined as introducing genetic information for therapeutic purposes. Besides the conventional strategy of protein replacement for congenital gene defects, gene therapy may have wide application, including vaccination against cancer and infectious diseases, regenerative medicine by in situ cell regulation by introducing “therapeutic” gene(s), and the ultimate goal of “gene” therapy by the technology of gene editing. In addition, cell therapy combined with ex vivo gene introduction is also a promising field.Messenger RNA (mRNA) is a new tool for introducing the genetic information. Direct delivery of mRNA into cells is highlighted as a safe and effective method without concerning the risk of random integration into the genome. Despite the fact that mRNA delivered in the body would be susceptible to highly active RNases that are ubiquitous in the extracellular space, we have established a drug delivery system (DDS) based on synthesized polymers, polyplex nanomicelle, to transport mRNA into target cells by preventing its degradation. We have already achieved in vivo mRNA administration for therapeutic purposes of various organs and tissues including brain, spinal cord, bone, articular cartilage, skeletal muscle, and liver. The mRNA-based therapy is indicated for treatment of various diseases including the fields of gene therapy, cell therapy, and regenerative medicine.

2. Generally-modified spheroid cell culture system for cell transplantation
Cell transplantation therapy is an attractive strategy for various medical fields. One serious problem is that the therapeutic effects may be limited by the death of transplanted cells or the decrease in cell activity due to unfavorable microenvironments such as ischemia, hypoxia, or inflammation. We established an injectable spheroid system for cell transplantation therapy, based on three-dimensional (3D) spheroid cell culture system for preserving cell-to-cell interaction using micropatterned plates coated with a thermosensitive polymer. In addition, the genetic modification of the cells using a biocompatible non-viral gene carrier, polyplex nanomicelle, was integrated for augmenting the therapeutic effects of cell transplantation. This system can be used for many applications of cell transplantation therapy.

3. Development of functional dental implants
Although dental implant treatment has already been clinically applied and excellent clinical progress has been reported, some cases demonstrate the unexpected disorder. Because natural teeth integrate the bone via periodontal ligament to exert their functions, the osseointegration, which is a healing form of current dental implant, is thought to be one of the causes. In this department, we are working on the development of periodontal ligament-bonded dental implant material, and we are trying to elucidate the mechanism of periodontal tissue homeostasis.

4. Interaction between biomaterials and the host tissues
To develop a new biomaterial for clinical applications, the material is requested to enhance biocompatibility and to decrease possible side effects in addition to its functionality. Biomaterials meet and interact with the living tissues at their interfaces. We evaluate phenomena of material-tissue interfaces and try to clarify the mechanism through material science and biological methods. These findings based on surface science contribute to develop new biomaterial designs.

The objective and principle of this graduate course is to educate students with materials knowledge demanded to medical and dental doctors who are leading medical professionals and bioscientists who are capable of carrying out their own research at an international level in the area of their special fields of science, respectively.