Functionalization And Biomedicine Application Of Poly(Lactide-co-glycolic Acid) Nanofibers

Biomedical materials can treat,repair or reconstruct damaged tissues and organs,and they are widely used in cardio-cerebrovascular,orthopedic,neurosurgery,drug delivery carrier,plastic surgery and other medical branches,which have become the key area and priority theme of national program for long-and medium-term scientific and technological development.The electrospun nanofiber with high porosity,large specific surface area and diverse functional design,can imitate directly or indirectly the natural tissue structure in micro and macro structure to repair or reconstruct tissue,which have unique advantages in biomedical fileds.This thesis centered on the electrospinning technology,constructed four PLGA-based bioactive composite nanofiber and focused on their biocompatibility and biochemical functions.(1)The temperature responsive shape-memory scaffolds(PLGA/CS@PLGATMC)were prepared by combining electrospinning and tape casting.The scaffolds were composed of an inner layer of aligned nanofibrous membrane of poly(lactide–glycolide)/chitosan(PLGA/CS)to regulate cell adhesion,proliferation and morphology and an outer layer of poly(lactide–glycolide–trimethylene carbonate)(PLGATMC)for programming the deformation.The smooth muscle cells(SMCs)behaviors and functions were dependent on the PLGA/CS ratios of membranes,and the scaffold with PLGA/CS 7:3 membrane exhibited the most suitable ability to regulate SMC behaviour,which was attributed to the coactions of the surface chemistry and nanotopography.Compared with the random nanofibers,the aligned PLGA/CS composite nanofibers were more favorable for cell growth.In addition,the PLGA/CS@PLGATMC scaffold could be deformed into a temporary planar at 20 °C for convenient seeding and attachment of SMCs and then immediately self-rolled into 3D tube at 37 °C.It was found that the smooth muscle cells on the three-dimensional tubular PLGA/CS@PLGATMC scaffold presented a high density of living cells,and the aligned nanofibers as the inner layer of the scaffold could induce the smooth muscle cells circumferentially oriented.Due to the excellent structural similarity and biocompatibility,temperature responsive PLGA/CS@PLGATMC shape-memory scaffolds have great potential in the application of small-diameter vascular scaffolds.(2)Based on ?-? conjugation and electrostatic attraction interaction between graphene oxide(GO)and polydopamine(PDA),PLGA-PDA-GO scaffolds were fabricated by immobilizing GO on PLGA electrospun nanofiber.In addition to the enhancement of thermal stability and mechanical strength,the surface roughness,hydrophilicity and electro-activity of the scaffolds were significantly improved by immobilization of GO.The scaffolds showed good inhibition of HT-29,and immobilized GO was observed to be in contact with but not internalized in HT-29 cells.The cytotoxicity mechanism of scaffolds towards HT-29 was attributed to intracellular activated reactive oxygen species that result from the physical interaction of the sharp GO edges and electrical signals of ?-? stacking between PDA and GO.The PLGA-PDA-GO scaffold had good inhibition of HT-29 cells and had potential application in inhibiting cancer cells.(3)Curcumin(Cur)was encapsulated into PLGA/CS fibers via electrospinning technology for the fabrication of p H responsive PLGA/CS/Cur composites.The encapsulated Cur still retained its antioxidant capacity which increased with the increase of Cur contents.The PLGA/CS/Cur composite nanofibers showed a good release control of Cur.The predominant release of Cur from composite fibers at p H 7.4 was Fickian diffusion;the release of Cur at p H 2.0 belonged to diffusion swelling mechanism.First-order model could well describe the diffusion behavior.As a p H response composite nanofibers,the accumulative release percentages of Cur from PLGA/CS/Cur was higher at p H 2.0 compared with 7.4 within the same period.In addition,the inhibition effect of PLGA/CS/Cur composite nanofibers toward HT-29 cells in an acidic environment was better than that in the neutral.The composite nanofibers could be used for p H responsive drug delivery.(4)PLGA/polylysine(PLGA/?-PL)composite nanofibers were constructed by incorporating bioactive ?-PL into PLGA nanofibrous mats via electrospinning technology.?-PL not only affected the surface chemical properties,but also enhanced thermal stability of the composite fiber scaffolds.Compared with pure PLGA,PLGA/?-PL composite nanofibers could provide more binding sites for cell adhesion,which was favourable to cell proliferation and differentiation.In addition,PLGA/?-PL composite nanofibers had good antibacterial activities toward S.aureus and E.coli.The antibacterial activity towards S.aureus was better than that towards E.coli due to the different cell membrane constituent and structure.The overall results demonstrated that the four electrospun PLGA-based composite nanofibers promise to be new biomedical materials for tissue engineering scaffolds,drug release and wound dressings,which can provide design strategies,theoretical and technical support for new PLGA-based composite nanofiber.