Development of watertight and bioabsorbable synthetic dural substitutes.

We have developed novel watertight and bioabsorbable synthetic dural substitutes. The substitutes were designed such that they had a three-layered structure, and each layer comprised a bioabsorbable copolymer prepared from L-lactide, glycolide, and epsilon-caprolactone. Various copolymers were synthesized, and appropriate compositions were selected for preparing the substitutes based on the results of leakage tests. Experimental substitutes that prevented the leakage of saline through the suture lines between the substitutes and dura mater were prepared. An in vitro study was performed in which the substitutes were sutured to porcine dura mater, and the amount of saline leakage was measured. It was demonstrated that leakage through the suture line could be completely suppressed by using the substitutes we developed along with favorable suturing techniques.

Enhancement of peripheral nerve regeneration using bioabsorbable polymer tubes packed with fibrin gel.

Nerve conduit tubes were developed using bioabsorbable polymer membranes, and the effects of tube shape--straight or bellows-shaped tubes--and the fibrin gel filling were investigated. The mechanical properties of the tubes were examined by in vitro tests, and their effectiveness for peripheral nerve regeneration was determined by grafting into experimentally transected sciatic nerves of rats. The bellows tube showed mechanically superior properties, and when used with the fibrin gel, it induced superior tissue formation of myelinated nerve fibers as compared to other tube types. The total area of myelinated axons regenerated in the fibrin-filled bellows tube was comparable to that of an isograft control, whereas those of the other tubes demonstrated inferior regeneration. This result suggests that the mechanically superior bellows tube filled with fibrin gel is an effective graft alternative for peripheral nerve regeneration.

Regeneration of peripheral nerves by bioabsorbable polymer tubes with fibrin gel.

We developed two types of nerve conduits, straight tubes, and bellows tubes, for peripheral nerve regeneration with bioabsorbable polymer membranes. Mechanical properties of these straight and bellows tubes were analyzed. 30 straight tubes and 30 bellows tubes were implanted to a nerve defect made in a rat sciatic nerve and the nerve regeneration in the tube was investigated. A half of these tubes were utilized alone and the others were filled with fibrin gel made from coagulated plasma and implanted. Bellows tubes were superior in mechanical characteristics to straight tubes and the inner cavities of the bellows tubes were suitably maintained after implantation. At 4 weeks after operations, remyelinations were observed in the regenerated tissue at the location of the middle parts of the tubes filled with fibrin gel whereas no remyelinations in the tubes without fibrin gel. The use of fibrin gel as filling materials within the tubes significantly enhanced the nerve regeneration. The fibrin gel might be soft nanomaterials significantly enhance the regeneration of the peripheral nerves. We concluded that the developed bioabsorbable bellows tubes filled with fibrin gel were effective for peripheral nerve regeneration.

Material design of bioabsorbable inorganic/organic composites for bone regeneration.

Two new bioabsorbable inorganic/organic composite materials were developed for bone regeneration. One material used was beta-TCP/PLGC in which poly(L-lactide-co-glycolide-co-epsilon-caprolactone) and beta-tricalcium phosphate were used as the matrix and filler, respectively. The other material used was HAp/Col-a soft nanocomposite of hydroxyapatite and type I collagen. Using these composites, two bone implants were designed. The efficacy of these implants was investigated by applying them to the critical-sized bone defects that were created in the canine tibia. Although no tissue engineering techniques such as application of growth factors or stem cells was utilized, successful healing was observed. These results suggested that bone regeneration in the critical-sized defects is possible without the use of growth factors or stem cells if the materials and the bone implants are suitably designed.

Development of guided bone regeneration membrane composed of beta-tricalcium phosphate and poly (L-lactide-co-glycolide-co-epsilon-caprolactone) composites.

To create biodegradable and thermoplastic materials for guided bone regeneration, GBR, and guided tissue regeneration, GTR, membranes, composites of beta-tricalcium phosphate, TCP, and biodegradable polyesters, poly (L-lactide-co-glycolide-co-epsilon-caprolactone), PLGC, and poly (L-lactide-co-epsilon-caprolactone), PLCL, were prepared by a heat-kneading method. The composites maintained thermoplasticity and mechanical strength by formation of a chemical interaction between Ca on TCP and C=O on the lactide segment of PLGC or PLCL. The composites also indicated composite effects in pH auto-regulation property and elongation of biodegradation period, e.g., the composites maintained their mechanical strength up to 12 weeks after soaking in both physiological and phosphate-buffered saline, and the period was sufficient time to use for GBR and GTR membranes. Animal tests for GBR indicated that the present composite membrane successfully regenerated beagles' mandible defects 10 x 10 x 10 mm3 in size. These results suggested that the TCP/PLGC bioresorbable composites could be utilized for GBR and GTR therapy.

Improved extension of platelet storage in a polyolefin container with higher oxygen permeability.

This study evaluated a newly developed polyolefin bag, which has a 50%/m(2) higher oxygen permeability to extend the shelf-life of platelets. Single-donor aphaeresis platelets were pooled, separated equally into two bags, PO-80 (0.8 l capacity) and KBP-PO (1 l capacity) for control, and stored in plasma for up to 7 d. Platelet biochemical and functional parameters were monitored in bags containing high (4.2 x 10(11)/250 ml/bag, n = 9) and low (2.0 x 10(11)/200 ml/bag, n = 3) concentrations of platelets over the storage period. After 7 d of storage, the PO-80 bags containing high concentrations of platelets had a better pH (mean pH 6.74) than those stored in KBP-PO (pH 6.32, P < 0.01); none of the nine PO-80 bags with a high platelet concentration had a pH below 6.2, compared with four of nine controls (P < 0.05). Similarly, lactate values were 20.19 mmol/l and 28.09 mmol/l respectively (P < 0.05). Aerobic metabolism was maintained better with greater O(2) consumption and less lactate generation in high-platelet concentration PO-80 bags than in the control bags. A significant difference was also found in pH, pCO(2) and lactate levels between the two bags containing low concentrations of platelets during the 7-d period. The in vitro characteristics of platelets declined less over 7 d when stored in a higher oxygen permeable container than in a marketed bag.

In vitro change in mechanical strength of beta-tricalcium phosphate/copolymerized poly-L-lactide composites and their application for guided bone regeneration.

Novel composites of bioactive beta-tricalcium phosphate [Ca(3)(PO(4))(2)] and biodegradable copolymerized poly-L-lactide (CPLA) were prepared by a heat-kneading method. The mechanical and chemical changes of the composites were evaluated in vitro by soaking in physiological saline and Dulbecco's phosphate buffered saline. When soaked in physiological saline, the 3-point mechanical strength decreased rapidly from 60 to 30 MPa in the initial 4 weeks and then gradually reached a plateau; the initial decrease in the mechanical strength was ascribed to the dissolution of beta-tricalcium phosphate from the surface. The mechanical properties evident at 8-12 weeks were sufficient for the composites to be used as a biodegradable material for regeneration of bone because the hydrolysis of CPLA was inhibited in both physiological saline and phosphate-buffered saline as a result of a pH-buffering effect. Composite membranes 250-microm thick were used to regenerate large bone defects in beagle dogs: 10 x 10 x 10 mm(3) in volume in the mandible and 20 mm in length in the tibia. The afflicted areas covered with the composite membranes were almost perfectly filled with new bone 12 weeks after the operation, whereas those covered with a CPLA membrane or without any membranes were invaded by soft tissue.