Growth factors delivery from PLGA microspheres within hyaluronic acid hydrogels for enhancing neural repair and angiogenesis: in vitro

摘要

Introduction: In this study, a biocomposite mimicking "niche" for promoting proliferation, differentiation and migration of neural stem cells (NSCs) as well as angiogenesis is to be developed for central nervous system (CNS) injuries treatment. Materials & Methods: BDNF and VEGF were loaded by poly(lacticco-glycolic acid) (PLGA) microspheres and then embedded in a cross-linked hyaluronic acid hydrogel for angiogenesis and support of NSCs in the CNS. The physical properties of the complex gels were evaluated by SEM, AFM and rheological tests. The BDNF and VEGF release kinetics were preformed by ELISA. Then the released factors were added to culture media of primary neurons and endothelial cells to assess the bioactivities, respectively. At last, NSCs were seeded in the gels and cultured for 5 days to study the survival and proliferation by morphology and CCK-8 test. Results & Discussion : The morphologies showed that growth factor-loaded microspheres of about 2 μm were embedded in the gel, which presented a typical rheological characteristic of hydrogel (Fig. 1,2). The encapsulated BDNF and VEGF were released sustainably and stably from PLGA microspheres and complex gels with an effective concentration at least for 150 hours (Fig.3). The bioactivities of the two factors were preserved well to promote the survival and growth of neuron and endothelial (Fig.4). In addition, NSCs survived and proliferated well when cultured in the gel which provided a good environment and support for them (Fig.5). Conclusion : This complex gels had a good potential for delivery of growth factors and neural stem cells for brain implantation. With the properties of angiogenesis and neurons protection as well as suitable to the brain tissue, it would be very useful in tissue engineering for brain tissue injury repair.