Fabrication Of PCL/PLGA Porous Material Based On Supercritical CO₂ Technology And Its Application In Tissue Engineering

The fabrication of scaffolds takes a key role in tissue engineering and the biodegradability and biocompatibility are essential for scaffolds.Have passed FDA certification,PCL and PLGA are officially listed as pharmaceutical excipients in the US Pharmacopoeia.PCL is a semi-crystalline polyester with good toughness and large elongation at break,while its degradation cycle is long and the melt strength is low,thus it cannot support cell structure in the microcellular foaming process.PLGA is biodegradable and holds good biocompatibility and controllable degradation rate.However,its low ductility and short degradation cycle restrict its clinical application in long-term tissue repairing.Therefore,blending PCL and PLGA can not only improve the degradation rate and the melt strength,but also can support the cell structure during the microcellular foaming process.Supercritical CO₂ foaming is known worldwide for its environmental friendly process and has been commonly applied in the fabrication of tissue engineering scaffolds.In this paper,a PCL/PLGA porous scaffold was fabricated based on supercritical CO₂ foaming technology.The foaming behavior and cell structure regulation were systematically studied.Then the mechanical properties were analyzed.Finally,Human umbilical vein endothelial cells?HUVECs?were cultured to evaluate the biocompatibility of the scaffolds.The works are listed as below:Chapter One:Blends with different PLGA contents were prepared by a twin-screw extrude and the phase morphology and rheological properties were studied.The morphology of the mixture showed that PLGA was uniformly dispersed in the PCL?act as matrix?,forming a typical sea-island phase structure,and the storage modulus and viscosity of the blends increased with the increasing PLGA content,which would contribute to support the cell structure during the foaming process.Then,taking 20%wt PLGA as an example,the effect of process conditions on cell morphology was systematically studied.Further,the blends was subjected to supercritical CO₂ foaming at 50?,2000 PSI,and 1 h and the effect of different PLGA content on the cell morphology was studied.It was found that as the increase of PLGA content,the diameter of the cell decreased and the cell density increased.This mainly due to the increase of heterogeneous nucleation points and the improved melt strength,which was correspondent to the properties of the blends mentioned above.Furthermore,the porosity and the open content of the scaffolds were analyzed and the main reason of the low porosity was the increased melt strength,which restricted the growth of the cells.The highest open cell ratio was discovered in10%wt PLGA,which is mainly due to the proper heterogeneous nucleation point and the moderate melt strength.The opening mechanism of foams with different PLGA content were analyzed.Chapter two:The mechanical properties of the porous scaffolds were investigated and the results showed that as the PLGA content increased,the compressive strength increased.The mechanical properties of the blend foam were predicted by the Gibson-Ashby model,and it was inferred that the elastic deformation of porous polymers with lower expansion ratios depends more on the cell walls than on the cells.Furthermore,the morphology of the cells subjected to different strains was observed by SEM,and the failure mechanism of the foam during compression was analyzed.Finally,the fatigue test results showed that the fatigue failure of the specimen cracked at one end,tore an opening,and then extended to the other end along an approximate straight line until a complete failure.The peak stress of the specimen showed a three-stage trend with the fatigue loading process:the initial stage,stable stage and acceleration stage.The strain energy density of the sample gradually decreased with fatigue loading,and the strain energy density of the 5%wt PLGA during cycling was higher than that of the other four groups,indicating that its fatigue resistance is better,which proved that the fatigue life of the 5%wt PLGA was the highest.Chapter three:Ultrasonic cavitation was applied in the process of the foam in order to fabricate an open-cell scaffold.It was found that the surface opening effect was the best at 0?,the cell diameter on the surface and density would increase as the ultrasonic time prolonged appropriately.HUVECs were cultured onto the porous scaffolds with different surface open-cell content.Live-Dead staining were used to observe cell proliferation,nucleus and F-actin were stained to observe the cell morphology on different scaffolds.The results showed that with the increase of the surface open-cell content,the number of living cells on the scaffold increased,and the cells with variable morphology spread evenly,and tended to connect each other.