Fabrication and characterization of aligned fibrin nanofiber hydrogel loaded with PLGA microspheres

Abstract

Developing novel biomaterials that deliver multiple regulatory signals is crucial to tissue regeneration by creating an ideal regenerative microenvironment. The purpose of the study is to develop a bioactive hydrogel delivering biomimetic joint regulatory cues of low elasticity, aligned structure, and neurotropic factors for nerve regeneration. Here a hierarchically aligned fibrin nanofiber hydrogel (AFG) loaded with drug-encapsulated poly(DL-lactic-co-glycolic acid) (PLGA) microspheres (PLGA@AFG) was prepared via electrospray and electrospinning. Firstly, drug-nanoencapsulated PLGA microspheres were prepared by electrospray method. Then electrospinning process was used to fabricate the aligned nanofiber hydrogel loaded with PLGA microspheres. Scanning electron microscope (SEM) and laser scanning confocal microscope were engaged to characterize the morphology and drug distribution of the composite hydrogel. The drug release behavior was observed by the use of Congo red as the model drug in vitro. The results proved the composite hydrogel maintained the aligned structure and soft properties of the AFG, and achieved a more reasonable drug release behavior for reducing the initial burst release comparing to the PLGA microspheres. Human umbilical mesenchymal stem cells (hUMSCs) were cultured on the PLGA@AFG composite hydrogel. The stem cells exhibited remarkable elongation along the long axis of the AFG with a bipolar morphology, indicating the good biocompatibility of the PLGA@AFG and the regulatory effect of the aligned structure on cell attachment.