Study On Structure Regulation And Biological Applications Of Electrospun Functional Fibrous Scaffold

Tissue defect and dysfunction caused by external injury and physical disease is one of the main hazards affecting human life and health,and also a major problem in clinical treatment.The development of biomedical materials provides an effective way to solve this problem.Among them,electrospun fibrous scaffolds have high specific surface area and extracellular matrix-like structure,which are conducive to cell adhesion and growth,showing great application prospects in the biomedical field.However,it is still difficult to meet the different needs of different tissues by relying only on the three-dimensional porous structure of fibrous scaffolds.Therefore,it is of great significance to accurately regulate the structure and function of fibrous scaffolds according to the specific pathological background（tissue microenvironment）.In this paper,we designed and prepared four different types of electrospun fibrous scaffolds for the purposes of fiber material structure regulation and performance optimization,and we investigated the fibrous scaffolds with different structures and functions to promote or inhibit different biological processes,such as skin trauma repair and malignant tumor treatment.The main research contents and conclusions of this paper are as follows:（1）Gradient topological fibrous scaffold for regional cell regulation:In this study,electrospinning technology and block copolymer self-assembly were combined to prepare fiber scaffolds with gradient micro/nano topology via selective solvent steam annealing,and the contact guidance effect of gradient structure on cell morphology,growth,migration behavior,and function was investigated.Material characterization revealed that during the selective solvent vapor annealing process,block copolymer molecular chains can self-assemble to form ordered nanostructures（lamellar and cylindrical nanostructures）,whereas oriented cylindrical fibers cross-link to form continuous film-like structures.In vitro cell experiments revealed that the scaffold with gradient micro-nano topology could guide cell morphology,migration behavior,and protein expression,as well as achieve regional cell regulation.（2）Fibrous scaffold with enhanced antibacterial activity and cell manipulation for promoting wound-healing:In this study,a photothermal responsive fibrous scaffold was fabricated by synthesizing therapeutic nano-agents with photothermal conversion performance and loaded with antibacterial drugs,and then loading them within aligned polycaprolactone/gelatin（PCL/Gel）fibrous matrix（with a melting point close to the photothermal treatment temperature）.The photothermal-chemo antibacterial activity and cell regulation of the prepared fibrous scaffold were studied in terms of skin wound repair.The results of material characterization revealed that near infrared（NIR）laser irradiation-triggered hyperthermia causes fiber melt,resulting in topology changes based on the photothermal conversion of therapeutic nano-agent and the lower melting point of the fibrous matrix.In vitro and in vivo tests revealed that hyperthermia,ciprofloxacin hydrochloride（CIP）and Zn²⁺released from fibers could effectively kill E.coli and S.aureus（antibacterial rate higher than98.5%）,and changes in fiber topological structure could realize stage-specific regulation of cell morphology and behavior.The prepared photothermal responsive composite fibrous scaffold can effectively promote the repair and regeneration of infected skin wounds.（3）pH/photothermal-responsive phase change fibrous scaffold for preventing postoperative tumor recurrence:In this study,the pH-responsive ZIF-8 shell was synthesized in situ on the surface of temperature-responsive polybutylene succinate/lauric acid（PBS/LA）phase change fibers.The photothermal conversion agent gold nanorod（GNR）and anti-cancer drug doxorubicin hydrochloride（DOX）were introduced into the core layer phase change fiber after its structure was optimized.A core-shell phase change fiber combined with photothermal and chemotherapy was prepared to investigate the application effect of the fiber scaffold in programmed drug delivery and tumor recurrence inhibition.The optimized core-shell phase change fiber has good photothermal conversion performance and photothermal stability,as demonstrated by material characterization.Core-shell phase change fibers exhibit stimulative and program-responsive drug release behavior when exposed to acid environment or laser irradiation.In vitro and in vivo experiments revealed that NIR laser-triggered hyperthermia and drug release could effectively remove residual tumor cells（tumor ablation rate is about 90.3%）,while also inhibiting tumor cell recurrence and metastasis.（4）Temperature-regulating phase change fiber scaffold for mild photothermal-chemotherapy of tumors:In this study,a composite phase change fiber with controlled drug release performance and temperature regulation effect was prepared by using porous carbon fiber as substrate loaded phase change material LA,anticancer drug DOX and heat shock protein inhibitor Apoptozole（Az）.The application effect of the fiber scaffold in postoperative mild photothermal-chemo therapy and alleviating hyperthermia damage to normal tissue cells was explored.The results of material characterization showed that the mass ratio of LA in the scaffolds was up to 84.5%,and the melting enthalpy was 151.5 J/g.Under NIR laser irradiation,the prepared fibrous scaffold exhibited excellent photothermal conversion performance,temperature regulation and photothermal responsive drug release behavior.Furthermore,in vitro and in vivo studies revealed that the composite phase change fibrous scaffold could effectively remove residual tumor cells while also minimizing the thermal damage to surrounding healthy tissues.