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Construction And Application Of Hierarchical Biomass Micro/Nano Structure Based On PLGA And Cellulose

Posted on:2022-01-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:D Q GaoFull Text:PDF
GTID:1484306608485764Subject:Biological materials engineering
Abstract/Summary:
Tissue engineering was an interdisciplinary consisting of engineering,chemistry,materials,cell biology and medicine.For biomimetic native tissue,tissue engineering scaffolds were designed to mimic hierarchical structure and dynamic behavior of extracellular matrix(ECM).Moreover,against the background of the lack of autologous organs and the severe immune response of allogeneic organs,tissue engineering scaffolds using renewable resources provided the potential solutions for tissue regeneration.Biomass materials were renewable resources,low cost of production,biodegradable,and biocompatibility.They can be extracted from agricultural or forestry plants,such as cellulose and polylactide(PLA),which were considered as alternatives to petro-materials.On the one hand,however,some biomass materials had worse solubility than synthetic polymers.On the other hand,biomass materials had heterogeneous structure,complicated components,and hardly controllable properties.Therefore,their high-value applications were limited in the field of biomedical materials.In this study,a synthesized polymer poly(vinyl alcohol)(PVA)was used as raw to prepare two-dimensional(2D)nanofibrous film and three-dimensional(3D)hydrogel.The basically fabricating approaches to tissue engineering were explored,and the scaffolds prepared using synthesized polymer were as a comparation with the scaffolds prepared using biomass materials.Then hybrid fabricating approaches were employed to produce hierarchical tissue constructs with micro and nano scales using PLGA and cellulose as raw materials for biomedical applications.Rat full-thickness excisional model and mice subcutaneously implantating model were employed to evaluate the 3D hierarchical micro/nano construct for wound healing and vascularization.Finally,the four-dimensional(4D)scaffolds were fabricated,the influence factors to its deformation were investigated.The research content can be catogried into 5 sections:(1)Electrospinning technology parameters were explored to fabricate 2D nanofiber membranes and investigate the influence factors to the morphologies of the nanofibers.PVA was electrospun from aqueous solution and crosslinked by ethanol solution and following by heat treatment to improve water stability of the PVA nanofibers.The whole preparing process is environment friendly.Inspired by the adhesive property of mussel,3,4Dihydroxyphenethylamine(DOPA)was incorporated into epidermal growth factor(EGF)protein by a bioorthogonal approach,which was more efficient binding to the scaffold than physical adsorption.(2)An antibacterial 3D PVA hydrogel loading silver sulfadiazine(AgSD)was synthesized by e-beam irradiation.Their properties that may be influenced by e-beam,such as crosslinking degree,antibacterial property,and biocompatibility,were investigated.AgSD was mixed with PVA solution in water suspension and ammonia solution,respectively.The results indicated that the AgSD in ammonia solution will release nano Ag particles after e-beam irradiation.However,its structure and antibacterial property were not influenced by e-beam irradiation,and when the concentration of AgSD was 0.35%,the hydrogel can kill the bacteria effectively.(3)A bilayer 3D scaffold with micro and nano topographies were constructed.Solvent exchange deposition modeling(SEDM)was developed using poly(lactide-co-glycolide)(PLGA)as raw materials.Compared to fused deposition modeling(FDM)3D printing polyester,SEDM printing microfibrous mesh showed better flexible property,its tensile strength was higher by 1.53 times than that of FDM samples.Electrospinning technology was employed to fabricate nanofibers packed onto the surface of flexible SEDM samples.The inner layer provided macropores for cells and tissues ingrowth.After SEDM printing samples were composited with electrospinning membranes,the nanofiber membranes served as outer layer.The tensile strength of the bilayer structure was improved by 1.57 times than that of SEDM samples.Moreover,nanofiber membranes can prevent bacterial invasion.After binding DOPAEGF to the bilayer scaffold,the hierarchical scaffold can successfully promote 16 mm of fullthickness wound healing of rats.(4)A degradable nanofibrous fibrin hydrogels were composited with a microfibrous aerogel to construct a biphasic gel with cross-scale microenvironment that can promote cell adhesion and support angiogenesis.Firstly,cellulose short microfiber with 100~2000μm of length and polyethylene(PE)short microfiber with 900 μm of length were employed to assemble into microfibrous aerogels using freeze-casting and heat crosslinking.The aerogels had macropores(>100μm)and high porosity(95.01%)can allow host cells or tissues infiltration.After compositing with the fibrin hydrogel,the biphasic gel can remain stable structure in water because the hydrogel phase provided viscous support and absorbed water.In the inadequate vascularization of subcutaneous(SUBQ)space of mice,the blood vessels density inside the biphasic gel can reach 74.73 vessels/mm2 after 6 weeks of SUBQ implantation.Compared to a composite of commercially surgical felt and fibrin hydrogel,the blood vessel density infiltration was approximate 2.3-fold higher in the biphasic gel after 4 weeks of SUBQ implantation.(5)A 4D tissue engineering scaffold was prepared by dispersing cellulose short microfiber and NIH3T3 cells into fibrin hydrogel matrix,wherein cells as actuators led the shape deformation of the biomaterial.The length and concentration of cellulose short fibers,and cell density can control its shape deformation.This 4D biomaterial platform was easy to handle and had great potential in the field of drug screening or 4D bioprinting.
Keywords/Search Tags:biomass materials, tissue engineering, hierarchical micro/nano structure, PLGA, cellulose
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