Injectable polymers （IP） are polymer materials exhibiting in situ sol-to-gel transition. The authors have studied temperature-responsive biodegradable IP forming hydrogels in response to increasing temperature （around body temperature）. Moreover, the authors have developed IP formulations exhibiting arbitrarily controllable duration time of gel state and expanded medical and pharmaceutical applications of the IP formulations. On the other hand, genetically engineered cells or stem cells themselves are emerging as novel pharmaceutical modalities. Cellular therapy is expected to be a treatment technique to overcome intractable diseases. In this paper, we introduce our recent studies of IP-assisted cellular therapies （myocardial infarction therapy and cancer immunotherapy）.

View full abstract

Through recent cell biology researches, phase transition/separation of biomolecules has emerged as an essential biophysical mechanism underlying subcellular organization of the cell. Membrane-less organelles, a class of intracellular structures assembled through phase transition/separation, are involved in a wide variety of both physiological and pathological phenomena. Membrane-less organelles are thus promising targets for arbitrarily manipulating cellular functions. In this review, the author summarizes development of synthetic biology molecular tools that manipulate assembly and disassembly of a representative membrane-less organelle, stress granules. Open challenges and future perspectives in the field will also be discussed.

View full abstract

Inflammation is defense system regulated by immune cells, and its dysregulation is implicated in various diseases. To improve the efficacy and safety of inflammatory disease therapies, biofunctionalized polymers have been designed and their nanoparticulation technologies have been developed. In this paper, we present the design of biofunctionalized biopolymers based on polyamines and hyaluronic acid and their application to the regulation of cellular functions. These polyamine-based therapies using biofunctionalized biopolymers may serve as a novel inflammation therapy against intractable inflammatory diseases such as ulcerative colitis.

View full abstract

Living cells are expected to be one of the functional active pharmaceutical ingredients, and the development of in vitro cell manipulation techniques are desired. Cells express their functions not only on the surface of the substrate but also in contact with biointerfaces of various dimensions such as molecular assemblies （nanogel aggregates） and hydrogel environments （three-dimensional environments） in vitro. Therefore, in order to develop new cell manipulation techniques, it is essential to prepare platform interfaces using biomaterials as elements focusing on biocompatibility and cell affinity. In this article, it is proposed that introduce a biointerface technology that extends cell affinity to various dimensions by molecular design of phospholipid polymers 2-methacryloyloxyethyl phosphorylcholine （MPC） polymers.

View full abstract

In this article, I will introduce our original photoresponsive materials and their applications to cell migration studies. The first one is a photoresponsive substrate for dynamic cell patterning. We investigated the influence of gravity vector on collective cell migration by inducing cell migration in the inverted state. The second one is an azobenzene-bearing hydrogel, whose stiffness changes by irradiation of UV/VIS light. We found the breast cancer cells exhibited transient epithelial-mesenchymal transition responses against sudden stiffening of the substrates.

View full abstract

When materials come into contact with biological fluids, water immediately adsorb onto the surface of materials. Water molecules play a crucial role in nanobiointerfacial interactions, including protein adsorption/desorption and cell adhesion/deadhesion on materials. To understand the role of water in the interaction of proteins and cells at biological interfaces, it is important to compare particular states of hydration water with various physicochemical properties of hydrated materials. Here, we discuss the fundamental concepts for determining the interactions of proteins and cells with hydrated materials along with selected examples corresponding to our recent studies, poly（2-methoxyethyl acrylate） （PMEA）, PMEA derivatives, zwitterionic polymers, poly（ethylene glycol）, and poly（2-oxazoline）s, and other polymers including biopolymers （DNA, RNA, proteins, and polysaccharides）. The states of water were analyzed by differential scanning calorimetry, time-resolved in situ attenuated total reflection infrared spectroscopy, solid-states NMR, surface force measurements, and wide variety of analytical techniques. We found that intermediate water which is loosely bound to a polymer, is a useful indicator of the biocompatibility of polymer surfaces. This finding on intermediate water provides novel insights and helps develop novel experimental models for understanding protein adsorption/cell adhesion in a wide range of polymers, and helps guiding principles to design functional polymers such as those used in biomedical applications.

View full abstract

Nepic^Ⓡ is an autologous cultured corneal epithelium for treatment of limbal stem cell deficiency approved in 2020 as the 1st regenerative medicine product in the ophthalmology field of Japan. Japan Tissue Engineering Co., Ltd. （J-TEC） has introduced the techniques developed by Prof. G. Pellegrini, a world authority on stem cell research, and established the manufacturing method of cultured corneal epithelium. Cells （enzymatically） isolated from patient’s own limbal tissue are cultured to produce the finished cultured corneal epithelium with maintaining corneal epithelial stem cells. Corneal epithelial stem cells from Nepic^Ⓡ provide corneal epithelial cells after transplantation and recover homeostasis of patient’s corneal epithelium.

View full abstract

In the injector market, the transition from in-hospital injection to home injection is accelerating due to changes in the market environment, awareness, and behavior, and expectations for the use of Motorized Digital Injectors are increasing year by year. Our company has developed the OSTABALO^Ⓡ Injector, which is a dedicated injector for the osteoporosis treatment drug OSTABALO^Ⓡ subcutaneous injection cartridge 1.5mg, which is manufactured by TEIJIN PHARMA LIMITED. This report describes our efforts in product development, the features of Motorized Digital Injector, the differences from non-Motorized Digital Injector, and considers the possibilities of Motorized Digital Injectors.

View full abstract