A.P. Pêgo

Copolymers of trimethylene carbonate and ε-caprolactone for porous nerve guides: Synthesis and properties

Copolymers of trimethylene carbonate and ε-caprolactone were synthesized and characterized with the aim of assessing their potential in the development of a flexible and slowly degrading artificial nerve guide for the bridging of large nerve defects. The effect of the monomer ratio on the physical properties of the polymers and its influence on the processability of the materials was investigated. Under the applied polymerization conditions (130°C, 3 days using stannous octoate as a catalyst) high molecular weight polymers (Mn above 93 000) were obtained. All copolymers had glass transition temperatures below room temperature. At trimethylene carbonate contents higher than 25 mol% no crystallinity was detected. A decrease in crystallinity resulted in the loss of strength and decrease in toughness, as well as in an increased polymer wettability. Amorphous poly(trimethylene carbonate), however, showed excellent ultimate mechanical properties due to strain-induced crystallization (Tm = 36°C). Low crystallinity copolymers could be processed into dimensionally stable porous structures by means of immersion precipitation and by combination of this technique with the use of porosifying agents. Porous membranes of poly(trimethylene carbonate) could be prepared when blended with small amounts of high molecular weight poly(ethylene oxide). Poly(trimethylene carbonate) and poly(trimethylene carbonate-co-ε-caprolactone) copolymers with high ε-caprolactone content possess good physical properties and are processable into porous structures. These materials are most suitable for the preparation of porous artificial nerve guides.

Biodegradable elastomeric scaffolds for soft tissue engineering

Elastomeric copolymers of 1,3-trimethylene carbonate (TMC) and epsilon-caprolactone (CL) and copolymers of TMC and D,L-lactide (DLLA) have been evaluated as candidate materials for the preparation of biodegradable scaffolds for soft tissue engineering. TMC-DLLA copolymers are amorphous and degrade more rapidly in phosphate-buffered saline (PBS) of pH 7.4 at 37 degrees C than (semi-crystalline) TMC-CL copolymers. TMC-DLLA with 20 or 50 mol% TMC loose their tensile strength in less than 5 months and are totally resorbed in 11 months. In PBS, TMC-CL copolymers retain suitable mechanical properties for more than a year. Cell seeding studies show that rat cardiomyocytes and human Schwann cells attach and proliferate well on the TMC-based copolymers. TMC-DLLA copolymers with either 20 or 50 mol% of TMC are totally amorphous and very flexible, making them excellent polymers for the preparation of porous scaffolds for heart tissue engineering. Porous structures of TMC-DLLA copolymers were prepared by compression molding and particulate leaching techniques. TMC-CL (co)polymers were processed into porous two-ply tubes by means of salt leaching (inner layer) and fiber winding (outer layer) techniques. These grafts, seeded with Schwann cells, will be used as nerve guides for the bridging of large peripheral nerve defects.

Preparation of degradable porous structures based on 1,3-trimethylene carbonate and D,L-lactide (co)polymers for heart tissue engineering

Biodegradable porous scaffolds for heart tissue engineering were prepared from amorphous elastomeric (co)polymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA). Leaching of salt from compression-molded polymer-salt composites allowed the preparation of highly porous structures in a reproducible fashion. By adjusting the salt particle size and the polymer-to-particle weight ratio in the polymer-salt composite preparation the pore size and porosity of the scaffolds could be precisely controlled. The thermal properties of the polymers used for scaffold preparation had a strong effect on the morphology, mechanical properties and dimensional stability of the scaffolds under physiological conditions. Interconnected highly porous structures (porosity, 94%; average pore size, 100 microm) based on a TMC-DLLA copolymer (19:81, mol%) had suitable mechanical properties and displayed adequate cell-material interactions to serve as scaffolds for cardiac cells. This copolymer is noncytotoxic and allows the adhesion and proliferation of cardiomyocytes. During incubation in phosphate-buffered saline at 37 degrees C, these scaffolds were dimensionally stable and the number average molecular weight (Mn) of the polymer decreased gradually from 2.0 x 10(5) to 0.3 x 10(5) in a period up to 4 months. The first signs of mass loss (5%) were detected after 4 months of incubation. The degradation behavior of the porous structures was similar to that of nonporous films with similar composition and can be described by autocatalyzed bulk hydrolysis.

Enhanced mechanical properties of 1,3-trimethylene carbonate polymers and networks

Poly(1,3-trimethylene carbonate), poly(TMC), has often been regarded as a rubbery polymer that cannot be applied in the biomedical field due to its poor dimensional stability, tackiness and inadequate mechanical properties. In this study we show that high molecular weight, amorphous poly(TMC) is very flexible, tough and has excellent ultimate mechanical properties. A number average molecular weight of 100,000 was determined to be a critical value below which the polymer has negligible mechanical properties and poor dimensional stability. This corresponds to a molecular weight that is 40 times higher than the molecular weight between entanglements. The dependency of the mechanical properties levels off at values above 200,000. This very high molecular weight poly(TMC) shows good recovery after mechanical deformation, considering that the only resistance to chain flow is due to chain entanglement. Poly(TMC) cross-linked upon gamma-irradiation, resulting in the formation of an insoluble network. The degree of cross-linking increases with the radiation dose. The final mechanical properties of the high molecular weight poly(TMC) rubbers improve upon irradiation. Especially, the creep resistance increased, while the Youngs modulus and tensile strength were not significantly affected. These biodegradable cross-linked rubbers may find wide application in soft tissue engineering where tough and elastomeric scaffolds are desirable.

Physical properties of high molecular weight 1,3-trimethylene carbonate and D,L-lactide copolymers.

High molecular weight statistical copolymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA) were synthesized and characterized with the aim of assessing their potential in the development of degradable and flexible materials for application in the biomedical field. Under the applied polymerization conditions (130 °C, 3 days using stannous octoate as a catalyst) monomer conversion was high or almost complete, and high molecular weight polymers (_Mn above 170 000) were obtained. Significant improvement of the mechanical performance of these materials was observed in comparison to results previously reported for TMC and DLLA based copolymers of lower molecular weight. For the entire range of compositions the polymers are amorphous with a glass transition temperature ranging between −17 °C for poly(TMC) and 53 °C for poly(DLLA). The polymers vary from rubbers to stiff materials as the content of TMC decreases. All polymers are hydrophobic with very low equilibrium water absorption (<1.5 wt %). Thermal analyses and tensile tests were performed on polymer samples after water uptake. Due to a plasticizing effect of the water, the thermal properties, and consequently the mechanical performance, of the copolymers with higher content of DLLA were the most affected. After water absorption, the polymer mechanical behavior can change from glassy to rubbery, as observed for the copolymer with 80 mol % of DLLA. The obtained results suggest that these copolymers are promising candidates as biomaterials in the preparation of degradable medical devices and systems.

Effect of nerve graft porosity on the refractory period of regenerating nerve fibers

OBJECT In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration. METHODS Microporous (1-13 microm) and nonporous nerve grafts made of a copolymer of trimethylene carbonate and epsilon-caprolactone were tested in an animal model. Twelve weeks after surgery, nerve and muscle morphological and electrophysiological results of regenerated nerves that had grown through the synthetic nerve grafts were compared with autografted and untreated (control) sciatic nerves. Based on the observed changes in the number and diameter of the nerve fibers, the predicted values of the electrophysiological parameters were calculated. RESULTS The values of the morphometric parameters of the peroneal nerves and the gastrocnemius and anterior tibial muscles were similar if not equal in the rats receiving synthetic nerve grafts. The refractory periods, however, were shorter in porous compared with nonporous grafted nerves, and thus were closer to control values. CONCLUSIONS A shorter refractory period enables the axon to follow the firing frequency of the neuron more effectively and allows a more adequate target organ stimulation. Therefore, porous are preferred over nonporous nerve grafts.