Study On Fabrication And Properties Of Biodegradable Polyesters Using Ferric Compounds As Catalysts For Esophageal Tissue Engineering Research

Aliphatic polyesters are one kind of biomedical materials which have been much studiedin recent decades. Among them, the biomaterials derived from poly（L-lactide）（PLLA） have beenwidely used in biomedical and pharmaceutical applications due to their low immunogenicity, goodbiocompatibility and be able to acceptance by living organism etc. However, there are two majorproblems in fabricating esophageal tissue engineering scaffolds using this kind of aliphatic estericpolymers. Firstly, the biomaterials based on PLLA were usually synthesized by the ring-openingpolymerization of cyclic ester monomer using stannum compounds as catalysts. The catalystmolecules covalently link to the ultimate product chain. When they were applied in vivo, stannumwill accumulate in body as the material gradually degraded, resulting in poisoning the human body.Secondly, the common polyesters have certain biodegradability and good cytocompatibility, buthave the defects in the mechanical strength and elasticity, which can’t meet the requirements ofsoft tissue engineering like esophagus and vessel, and particularly, retard the development of theesophageal tissue engineering..According to the requirements of the scaffold properties in esophageal tissue engineeringresearch, a series of polyester materials were prepared using low toxic ferric compounds ascatalysts. Firstly, the ring-opening polymerization of L-lactide （L-LA） and copolymerization of L-LA and ε-caprolactone （ε-CL） using ferric compounds like FeCl₃, iron（III） acetylacetonate（Fe（acac）₃）, iron（II） acetylacetonate （Fe（acac）₂） and iron（III） ethoxide as catalysts wereinvestigated. The polymeric products were characterized by technologies including GPC,¹HNMR, ICP-AES and DSC. From the results, we concluded that Fe（acac）₃and Fe（acac）₂were theefficient catalysts. The optimal reaction conditions were as follows, the reaction temperature1300C,[n （catalyst）/n （L-LA）]1.0×10^-3and the reaction time32h. The catalytic reaction belongs tothe coordination-insert mechanism.Secondly, an oligomer poly（lactide-co-ethylene glycol-lactide） dimethacrylate （PLEGDMA）was synthesized using Fe（acac）₃as the catalyst. It was further used to react with polyethyleneglycol diacrylate（PEGDA） and N-isopropyl acrylamide （NIPAAm） upon UV irradiation to form a degradable cross-linked polymer. PLEGDMA was analyzed to confirm its chemistry using FTIRspectroscopy,1H NMR spectra and Gel Permeation Chromatography （GPC）. The thermodynamicproperties, mechanical behaviors, surface hydrophilicity and degradability of the cross-linked filmswere systematically evaluated by differential scanning calorimetry （DSC）, tensile tests and contactangle measurements. The effects of reaction variables such as PEGDA content and reactants ratiowere optimized to achieve a material with excellent properties. It can be concluded that F-2k,which was prepared from the prepolymer obtained by the copolymerization of PEG（Mn,2000Da）and L-LA with the best ratio, was determined to be the optimising substrate with a lower Tg, highermechanical strength, better hydrophilicity and degradability than those of all other specimens.Using a tubular mold patented in our group, a tubular scaffold with predetermined dimension andpattern was fabricated, which aims at guiding the growth and phenotype regulation of esophagealprimary cells like fibroblast and smooth muscle cell towards fabricating tissue engineeredesophagus in future.Finally, fibroblasts and SMCs were seeded on the F-2k materials. The morphology andgrowth of both cells were characterized individually by cell number counting, SEM, H&E andimmunohistochemistry staining etc. It was concluded that cells can grow well on the films. Theymaintain their morphology and functional differentiation after cultured in vitro for7days,according to the immunohistochemistry analysis. Therefore, the cross-linked PLLA-based polymerfabricated under the present protocol is biocompatible. It is expected to be useful as esophagealtissue engineering scaffold materials which will promote esophageal tissue engineering researchand clinical application in future.