東京大学 伊藤研究室

Center for Disease Biology and Integrative Medicine Faculty of Medicine, The University of Tokyo

Japanese

Research

Introduction of research areas in Ito Lab;

  • Research area 1: Hydrogels for medical uses
  • Research area 2: Particles for medical uses: from nano to micro
  • Research area 3: Application to disease treatments

Research area1:Hydrogels for medical uses

Injectable hydrogels are highly anticipated for use in minimally invasive treatments. Using natural polysaccharides and proteins as backbone, we fabricated in situ hydrogels cross-linked via biocompatible chemical reactions. Since hydrogels are easy to handle, they are anticipated for use in various areas, such as scaffolds for tissue regeneration, drug carriers, adhesion barriers, hemostatic agents and many more.

Hyaluronic acid is commonly used as a polymer backbone due to its high biocompatibility, and is important in cosmetic products, contact lens and many other health care products. Dextran, cellulose and starch derivatives, ionically cross-linkable alginate, positively charged chitosan, cell adhesive collagen and gelatin, keratin are other examples of polymer backbones.

Since natural polymers are limited in design flexibility, synthetic polymers are important to biomaterials as well. With progress in techniques for polymer synthesis, dendritic polymers have become popular in industry. With merits like low viscosity and easy surface modifications, they are gaining popularity as foam and paper coating materials. In our lab, we synthesized a novel nano-sized star polymer using chemically modified polymers as building units for future application to medically used hydrogels, as well as to colloidal dispersion system.

Other than fabrication, we also research on application process of biomaterials. The structure and functions of biomaterials are heavily dependent on both the starting material and process. As such, chemical engineering plays an important role. We are examining the gelation process using static mixers and atomizers as methods of application.

Research area2: Particles for medical uses: from nano to micro

We are synthesizing fine particles for various medical uses. Other than material composition, the size, shape and morphology are also important in determining the functions of the fine particles.

Particles of nano-order size are called nanoparticles, and they exhibit properties not found in bulk objects. For example, silicon nanoparticles used in semiconductors show fluorescence, gold nanoparticles are colored red with surface plasmon. Making use of these features, we are developing nanoparticles for imaging and drug delivery carriers.

Also, we are developing anti-cancer drug-incorporated hyaluronic acid nanogels that are spontaneously formed thorough metal coordination. Their sizes range from 10nm to hundred nm, lying in between the size of nano particles and micro particles. We aim to achieve effective drug delivery by making use of cell-ECM adhesion and ECM turnover.

Micro particles are used as drug carriers via intramuscular injection, and drug-eluting beads for embolization. Our lab focuses on the SPG membrane emulsion technique for fabrication of highly uniform micro-particles. In our lab, we are developing hemoglobin encapsulated oxygen carriers (artificial red blood cell), and drug-drug-eluting beads for embolism.

Artificial oxygen carriers prepared by membrane emulsification range from 1-20um in diameter, while those synthesized by atomizers are about 150um in diameter. As shown below, using functionalized ionically cross-linked polymers, we are developing cell-encapsulating microcapsules for use in artificial endocrine pancreas.

Research area3:Application to disease treatments

We are collaborating with the University Hospital and off-campus medical institutions to utilize hydrogels and micro-particles in treatments of diseases.

Regenerative medicine and tissue engineering

The concept of tissue engineering was proposed by a group of researchers at MIT/MGH in the 1990s. By controlling the interaction of cells, scaffolds and humoral factors, generation of artificial tissues was thought to be possible. Injectable hydrogels and microcapsules are examples of scaffold materials. In our lab, with a focus on bone and islet regeneration, we look at differentiation of cell encapsulated in hydrogels, functional expression through transplants, and angiogenesis.

Drug delivery system

DDS refers to the technique of delivering the minimum required amount of drugs to a targeted location, at a targeting timing. One fundamental concept of DDS is sustained drug release. Drug concentrations above the limit will increase side-effects, whereas drug concentrations within the limit will not result. By maintaining the desired drug concentration range over long periods of time, not only will side effects and dosage be minimized, QOL improvements can be expected. We are researching on DDS for localized administration to peritoneal dissemination of gastric cancer, mesothelioma, and liver cirrhosis.

Tissue adhesion barriers and hemostatic materials

Adhesions of peritoneal organs to neighboring organs, or peritoneal membrane after abdominal or laparoscopic surgeries, is commonly known as peritoneal tissue adhesion. The repeated resection of the liver in hepatectomies give rise to high occurrence of adhesion formation. This greatly reduces the safety of surgeries, as well as lengthens surgery time. Taking advantage of the merits of injectable hydrogels, we seek to fabricate novel adhesion barriers possible for laparoscopic use.

Hemostasis is critical during surgical procedures. Since most available hemostats are composed of fibrin sealants and collagen-based materials, we are researching on fabrication of effective hemostats using materials not derived from the blood.

These medical devices are key to minimally invasive treatments, and indispensable to safe clinical practices.