| POLYMERS Vol.66 No.9 |
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COVER STORY
Polymers for Modern Medical Treatment |
| COVER STORY: Highlight Reviews |
| Development of Small-Diameter Vascular Graft Made from Silk | Tetsuo ASAKURA |
| <Abstract> Bombyx mori silk fibroin (SF) fiber is a well-known excellent fiber for textile. However, the SF fiber has also a long history of use in sutures. There are large demands for surgical revascularization of small-diameter (less than 6 mm in diameter) vascular grafts, but no available artificial grafts at present. Thus the SF was used as artificial blood vessel material. The grafts with 1.5 mm in inner diameter and 10 mm in length, were implanted into rat abdominal aorta by us and proved to be excellent grafts with remarkably high patency (ca. 85%, n = 27 at 12 months) after grafting with remodeling. Endothelial cells and smooth muscle cells migrated into the SF graft early after implantation, and became organized into an endothelium and a media-like smooth muscle layer. Several attempts of the preparation of SF grafts and the animal implantation experiments are described together with the scope of the future works about the development of the small-diameter SF vascular grafts. Keywords: Bombyx Mori Silk Fibroin / Small-Diameter Vascular Graft / Patency Remodeling / Endothelium / Smooth Muscle Layer |
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| Polymer Nanomedicine | Yukio NAGASAKI |
| <Abstract> Reactive oxygen species (ROS) are known to play various roles in many important events in vivo. However, excessive production of ROS causes significant adverse side effects to the living body. Numerous drugs have been applied to reduce excessive amounts of generated ROS. However, low molecular weight (LMW) antioxidants spread non-specifically to the entire body and internalize in healthy cells. Because the living body obtains energy via the mitochondrial electron transport chain, such LMW antioxidants suppress this kind of normal redox reaction to cause severe damage to normal organs and the body. In order to improve the selective anti-oxidant character in vivo, we have designed redox polymer nanomedicines (RNP), which possess self-assembling character in aqueous media. Because RNP hardly internalize in healthy cells, it showed extremely low toxicity in vivo, unlike LMW antioxidants. The author introduces recent progress in redox nanomedicine in this review. Keywords: Nanomedicine / Antioxidants / Nanoparticles / Injectable Gels / An Electron Transport Chain / Cancer / Alzheimer’s Disease / Ulcerative Colitis / Tissue-Antiadhesive / Peritoneal Dialysis |
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| An Innovative Surgical Sealant with Strong Bonding Strength | Ryo MIZUTA, Akihiro NISHIGUCHI, Tetsushi TAGUCHI |
| <Abstract> Surgical sealants are widely used clinically. Fibrin sealant is a commonly used sealant, but is ineffective under wet conditions during surgery. In this study, we developed surgical sealants composed of hydrophobically modified Alaska pollock-derived gelatins (hm-ApGltns) with different alkyl chain lengths from C3 to C18 and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG). The burst strength of the hm-ApGltns-based sealant was evaluated using a fresh porcine blood vessel and was found to increase with increasing alkyl chain length. The maximum burst strength was observed when stearoyl-group modified ApGltn (C18-ApGltn)/4S-PEG based sealant was used, displaying 3-fold higher burst strength than the original ApGltn (Org-ApGltn)/4S-PEG sealant, and 10-fold higher than the commercial fibrin sealant. C18-ApGltn/4S-PEG based sealant was biodegraded in rat subcutaneous tissue within 8 weeks without severe inflammation. Therefore, the developed sealant has potential applications in the field of cardiovascular surgery as well as thoracic surgery. Keywords: Tissue Adhesive / In Situ Gel / Gelatin / Fish / PEG |
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| COVER STORY: Topics and Products |
| Development of Polylactic acid Micro Blood Collection Needle Aimed for Zeroing Infectious Garbage of Medical Needles by Learning from Nature | Mitsuo FUKUDA |
| <Abstract> I was often asked “why did you think about developing a blood collection needle with polylactic acid”. When I worked at a medical equipment company, there were some cases where drugs leaked from the affected part of a syring due to the pressure applied at the time of the drug administration, resulting in peritonitis and death. Because I witnessed this, I thought that it would be better if the needle and the medicine are unified when the injected medicine is administered into the body. It is better if the needle can directly reach the affected part and can be directly administered without leaking the medicine. This was the trigger for development of a new system. This is a product of imagining that the body will absorb the needle and the medicine togerther without using an injection metal needle and a syringe. As a necessary condition for realization, I thought that a safe and secure medical needle other than a metal needle is indispensable, starting from the point of whether it is possible to make a needle using a biocompatible material. The needle was perfected by experimentation and testing. Keywords: Biocompatible & Biodegradable Polymer / Biomimicry / Polymer Needle / Vaccination / DDS / Medical Waste / Medical Device / GLP / Blood Lancet / Sharps Injure / Second Infections |
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| Development of Novel Polymer Based Pre-Fillable Syringe that can Resolve Serious Issues for Biopharmaceutical Drugs | Yoshihiko ABE |
| <Abstract> Pre-fillable syringes, which are widely used as containers of biopharmaceutical drugs, have some problems that need to be resolved for the stabilization of biopharmaceutical drugs. Among some issues, we selected four serious problems that are protein aggregation by silicone oil, breakage of glass barrels, protein oxidation and aggregation by radicals, and drug denaturation by leachables from the syringe system. We developed new technologies to resolve these issues. To eliminate the breakage with barrels and reduce protein aggregation, polymer based syringe systems were developed with silicone oil free technology called i-coating®. In addition, by choosing low extractable contact materials and selecting steam sterilization, we could achieve a low leachable syringe system called PLAJEX®, which can minimize protein oxidation and aggregation. These new syringe systems can keep the biopharmaceutical drugs stable and attribute to maximum drug efficacy. Keywords: Cyclic Olefin Polymer / Chlorinated Butyl Rubber / Silicone Oil Fee / Sterilization / Extractable and Leachable / Stability / Protein Oxidation / Protein Aggregation |
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| Development of Thermo-Responsive Cell Cultureware, UpCell®, for Regenerative Medicine | Setsuko HASHIMOTO |
| <Abstract> The cell sheet engineering technology was developed by Prof. Teruo Okano of Tokyo Women’s Medical University. Cells grown to confluency on the intelligent cultureware coated with temperature-responsive polymers (poly(N-isopropylacrylamide)：PIPAAm) can be detached from the surface without enzymatic digestion but just by lowering the temperature. CellSeed developed a series of cultureware products (UpCell®). In collaboration with academia, CellSeed is also developing therapeutic applications such as esophageal epithelium cell sheets and regeneration of cartilage tissue using cell sheets. Endoscopic Submucosal Dissection (ESD) has become very popular as an early phase treatment of the esophageal cancer. The stricture formation of the esophageal duct after ESD needs to be overcome. Ohki et al. at Tokyo Women’s Medical University have developed a new treatment using cell sheets prepared from the patient’s oral mucosa to prevent the stricture. CellSeed is running a clinical trial in Japan aiming to obtain a product license. Keywords: Thermo-Responsive Surface / Nanometric Poly(N-isopropylacrylamide) Layer / Cell Sheet Engineering / Regenerative Medicine |
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| Polymer Science and I: A Personal Account |
| In the Research of Interfaces | Daiki MURAKAMI |
| <Abstract> The author has coninued the research of “Interfaces” for the last 15 years. The knowledge of basic physical chemistry and many good human connections always helped the author in his change of research areas from liquid interfaces to polymer interfaces, and finally to bio interfaces. |
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| Front-Line Polymer Science |
| Self-Healing of Tough Polymers by Ubiquitous Stimuli | Naoko YOSHIE |
| <Abstract> Polymers crosslinked with dynamic bonds potentially have self-healing ability. Macroscopic breaking and healing of such polymer materials correspond to dissociation and re-association of the dynamic bonds, respectively. When thermodynamically controlled, these polymers definitely heal under any conditions. However, due to the reduced mobility of macromolecules, dynamic bonds in rigid polymers cannot display re-bonding ability under most practical conditions. So, healing is usually controlled by kinetics and allows to proceeds only in soft and flexible polymers. In this review, recent attempts to strengthen autonomous healing polymers and design strategies of rigid polymers that can heal by ubiquitous stimuli such as heat and immersion in solvent, solution of crosslinking agent and water. Keywords: Self-healing / Dynamic Bond / Mechanical Strength / Autonomous Healing / Water-Assisted Healing |
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