S.-H. Hyon

Thermal characterization of polylactides

Abstract Three important thermal characteristics of polylactides have been measured and discussed. These are glass transition temperature, melting temperature, and degradation behaviour. The glass transition temperatures at infinite molecular weight for l - and d,l -optical isomers were 58 and 57°C, respectively. Melting temperature for the crystalline l -isomer was 184°C at infinite molecular weight. Number-average molecular weight, melt viscosity, differential scanning calorimetry, infra-red analysis and thermogravimetric analysis were used to study the degradation behaviour under different conditions. Polylactides were found to be highly sensitive to heat, especially at temperatures higher than 190°C. Most of the degradative reactions were thought to involve the highly concentrated ester bond on the main chain. These reactions included thermohydrolysis, depolymerization and cyclic oligomerization, intermolecular and intramolecular transesterifications. Low molecular weight compounds associated with the polymer seemed to play an important role in lowering the molecular weight at high temperatures, as well as the hydroxyl end group of the main chain. The compounds include water, monomers, oligomers, and polymerization catalysts. Removal of the non-polymeric contents and blocking the hydroxyl end-group enhanced the thermal stability of the polymers. The increased amount of the polymerization catalyst in the end product contributed to the degradative reactions.

Polymer-hydroxyapatite composites for biodegradable bone fillers

A number of composites made from biodegradable polymers and hydroxyapatite were studied in vivo and in vitro in an attempt to develop biodegradable artificial bone fillers. Histological observation in rats revealed that polylactic acid, of low molecular weight (PLAoligomer), was rapidly resorbed and replaced by newly formed bone tissue when incorporated with hydroxyapatite and this suggested that the incorporated hydroxyapatite seemed to play an active role in the new bone formation. In vitro testing revealed that the solubility of hydroxyapatite was markedly enhanced when mixed with PLAoligomer.

Development of an artificial articular cartilage

Abstract We have attempted to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which lubrication and load-bearing mechanisms of natural and artificial joints are compared. We investigated poly (vinyl alcohol)-hydrogel (PVA-H) which has been recognized as a rubber-like gel and have improved the mechanical properties of this gel through a new synthetic process. In this article we report the biocompatibility and various mechanical properties of the new, improved PVA-H from the aspect of its usefulness as artificial articular cartilage. As regards the lubrication, we measured the change of thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading and found that the PVA-H had a thicker fluid film under higher pressure than polyethylene (PE). The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times as large as that of PE. Histological findings of the articular cartilage and synovial membranes around the PVA-H implanted for 8–52 weeks showed neither inflammatory nor degenerative changes. The PVA-H artificial articular cartilage could be attached to the underlying bone using an osteochondral composite material. Although there remain still some problems to solve, PVA-H seems to be a very interesting and promising material which meets the requirements of artificial articular cartilage.

Preparation of transparent poly(vinyl alcohol) hydrogel

A transparent hydrated gel is prepared from a poly(vinyl alcohol)(PVA) solution in a mixed solvent consisting of water and dimethyl sulfoxide(DMSO). Upon cooling the PVA solution below the room temperature, a gel is formed as a consequence of crystallization of PVA molecules. Exchange of DMSO in the formed gel with water gives the hydrated PVA gel which is high in tensile strength, water content, and light transmittance.

Effects of residual monomer on the degradation of DL-lactide polymer

The effects of remaining monomer on hydrolysis of poly(DL-lactide) were examined by adding different amounts of monomer to purified polymer samples. The existence of monomer in the polymerization products was found to enhance hydrolytic degradation of the polymer. A porous texture was observed on the SEM photographs of degraded materials, which led to the conclusion that the remaining monomer enabled water molecules to gain better access to the polymer matrix through this porous structure. The effects of molecular weight and chemical composition of polylactides on the hydrolytic degradation were also studied. Poly(DL-lactic acid) with higher molecular weights showed longer retention of the initial properties such as molecular weight and tensile strength. Copolymerization of DL-lactide with glycolide enhanced the hydrolysis, probably because of increased hydrophilicity of the polymers.

Evaluation of a bilayer artificial skin capable of sustained release of an antibiotic

A bilayer artificial skin, composed of an upper silicone sheet and a lower collagen sponge, has been developed by modifying a technique proposed by Yannas and Burke. We have applied it clinically with success, but infection sometimes occurred in the area where the artificial skin was placed. To use it safely in an infected wound, we developed a new type of artificial skin capable of sustained release of antibiotic. Microspheres of poly-L-lactic acid containing an antibiotic, were installed in the upper silicone sheet. The usefulness of the new type of artificial skin was suggested by in vitro studies.

Melt Spinning of Poly-L-Lactide and Hydrolysis of the Fiber in Vitro

It has been widely recognized that biocompatibility of a polymeric material is the minimal requisite for use as a surgical implant. What we mean by the biocompatibility is different from one implant to another, depending on the purpose and the duration of implantation. For instance, nonthrombogenicity is required for the material to be used as a small vascular graft, while strong bioadhesion with host tissues is needed if the polymer is used for artificial tracheas. On the other hand, soft biomaterials are often demanded which give no mechanical stimulus to the surrounding tissue, as IUD and contact lens. The biocompatibility involves all of these properties, implying that it is difficult to give a clear single definition to the term “biocompatibility”.

Controlled cisplatin delivery system using poly(D,L-lactic acid)

Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe.

Preservation of rat aortic tissue transplant with green tea polyphenols.

Green tea polyphenols have recently attracted medical attention as bioactive agents with anticancer, antimicrobial, and antiviral effects. We discovered their new usage as preservative agents for tissue transplants. We preserved rat aortas in a DMEM solution containing polyphenols extracted from green tea leaves. The preserved aortas retained original structures and mechanical strength, and were devoid of any undesirable cell secretions for over a month under physiological conditions. In addition, aortas from Lewis rats preserved for a month and transplanted to allogenic ACI rats completely avoided rejection by the host, suggesting that the polyphenols have immunosuppressive actions on the aortic tissues. From these results, we conclude that polyphenol treatment of aortic tissue transplant can maintain its viability for extended periods of time either before or after transplantation, and the method can be applicable to other transplantation situations.

New biodegradable oligoesters for pharmaceutical application.

Tartaric acid, malic acid, and glyceric acid were copolycondensed with glycolic acid at various molar ratios in feed to quickly synthesize biodegradable oligoesters. They were likely to have a moderately cross-linked structure with relatively low molecular weights and hydrophilic groups on the chains. In addition to macroscopic gels which were insoluble in any solvents, we could obtain the oligoesters which were insoluble in water but soluble in N,N-dimethylformamide. The degradation rate of the oligoesters was higher than that of lactic acid (LA) oligomers having molecular weights of a few thousands. On the contrary, their glass transition and flow temperatures were much higher than those of LA oligomers, indicating that their handling during the preparation of drug delivery dosage forms was much improved. The formulation of microspheres containing drugs from the oligoesters revealed that they were useful as biodegradable matrices having high degradation rates.