Synthesis, Characterization Of Poly(Butylene Succinate)s And Fundamental Research As Novel Biomaterials

Poly(butylene succinate) (PBS) has also been known as an important biodegradable aliphatic polyester and has attracted much interest because of its good degradation properties, excellent physical properties and processability. Due to these advantages, PBS's potential application as a novel biomaterial has been concerned; however there is little research about its fundamental evaluations for biomedical application. The in vitro biodegradation, cell cytotoxicity and cell biocompatibility of PBS, which is important to the application and development as a novel biomaterial, are studied here. A new wave of advances in modern medicine is enabling the production of a new generation of smart biomaterials. The incorporation of functional pendent groups, such as NH2, into PBS main chain is expected to possess the following advantages: (1) The presence of the functional pendent groups should result in enhanced hydrophilicity of the polymers and changing main chain structure of the polyesters, thus leading to a controllable degradation rate; (2) The hydrophilic pendent groups could tune the hydrophilic–hydrophobic balance and surface charge distribution of the polyesters, which could enhance the cell biocompatibility of material. Particularly, it provides an opportunity for covalently attaching drugs, peptides and other bioactive reagents onto the polymers, which is expected to respond to specific cellular signals. These functional polymers are expected to be used as the drug carriers in targetable and controlled delivery and intelligent scaffolds materials in tissue engineering. In this dissertation, we synthesized the PBS, PES and PBES copolyesters and further systematically discussed their in vitro biodegradation behaviors, cell cytotoxicity, cell biocompatibility and anticoagulant activity. Meanwhile, we synthesized a novel copolyester poly(butylene succinate-co- butylene aspartic acid) with lateral amine groups by melt condensation polymerization and discussed the relationship between aspartic acid contents and biodegradation behaviors, cell cytotoxicity, cell biocompatibility and anticoagulant activity. The main results of this work are summarized as follows:(1) PBS, PES and PBES were synthesized by polycondensation of 1,4-butanediol (B) with succinic acid (S) and ethylene glycol(E)using Ti(Oi-Pro)4 as the catalyst. The polymerization reaction process and the properties of copolyesters were discussed in detail.(2) Systematically discussed the potential of PBS, PES and PBES as novel biomaterials. The PBS, PES and PBES films would degrade not only by lipase Novozyme 435 but in the phosphate-buffered saline. The results suggested that the biodegradation behavior showed different phases: fast in first and got slow in second phase by Novozyme 435 while slow in the first and got accelerated in the second phase in the phosphate-buffered saline. The ethylene glycol contents of main chain related to the degradation rate by Novozyme 435 while had no significant correlation with that in the phosphate-buffered saline. MTT cytotoxicity assay showed that PBS, PES and PBES have no evident cytotoxicity. The cell attachment and cell cultivation experiments demonstrated that PBS, PES and PBES exhibited good cell biocompatibilities. In vitro tests showed PBS, PES and PBES have good antithrombogenecity. Therefore, these results provide the possibility that PBS, PES and PBES could be applied as an alternative novel biomaterial; especially for absorbable suture, absorbable bone nails,vascular prosthesis and tissue engineering scaffold.(3) A novel biodegradable copolyester poly(butylene succinate-co-butylene aspartic acid) with lateral amine residue has been synthesized through a condensation copolymerization and Pd/C catalyzed hydrogenation. The polymerization reaction process and the properties of copolyesters were discussed in detail.(4) Systematically discussed the relationship between the contents of aspartic acid and biomedical preoperties of copolyesters. P(BS-co-BCD) and P(BS-co-BD) exhibited good hydrophilicity than PBS. The degradation behavior of P(BS-co-BCD) had significant correlation with the contents of aspartic acid, the degradation rates of P(BS-co-BCD) increased with increasing contents of aspartic acid. The degradation behavior of P(BS-co-BCD) and P(BS-co-BD) were no significant differences. MTT cytotoxicity assay showed that P(BS-co-BCD) and P(BS-co-BD) have no evident cytotoxicity. The cytocompatibility experiments demonstrated that P(BS-co-BD) with NH2 functional groups showed better cell biocompatibilities as compared with the PBS for their better hydrophilic–hydrophobic balance and surface charge distribution. In vitro antithrombogenicity tests showed P(BS-co-BCD) and P(BS-co-BD) have good antithrombogenecity.(5) The preliminary applied performance of P(BS-co-BCD) in drug release was studied. A series of P(BS-co-BCD) microcapsules containing indometacin were prepared by emulsion solvent evaporation technique.