title: Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells.
abstract: OBJECTIVE
  To develop a biomaterial composite for promoting proliferation and migration of neural stem cells (NSCs), as well as angiogenesis on the materials, to rescue central nervous system (CNS) injuries.
  
  
  METHODS
  A delivery system was constructed based on cross-linked hyaluronic acid (HA) hydrogels, containing embedded BDNF and VEGF-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery and support for NSCs in the CNS. The surface morphologies were evaluated by SEM and AFM, mechanical property was investigated by rheological tests, and release kinetics were performed by ELISA. Bioactivity of released BDNF and VEGF was assessed by neuron and endothelial cell culture, respectively. Compatibility with NSCs was studied by immunofluorescent staining.
  
  
  RESULTS
  Release kinetics showed the delivery of BDNF and VEGF from PLGA microspheres and HA hydrogel composite were sustainable and stable, releasing ~20-30% within 150 h. The bioactivities preserved well to promote survival and growth of the cells. Evaluation of structure and mechanical properties showed the hydrogel composite possessed an elastic scaffold structure. Biocompatibility assay showed NSCs adhered and proliferated well on the hydrogel.
  
  
  CONCLUSIONS
  Our created HA hydrogel/PLGA microsphere systems have a good potential for controlled delivery of varied biofactors and supporting NSCs for brain repair and implantation.
authors.affiliation: Beijing Institute for Neuroscience, Beijing Center of Neutral Regeneration and Repair, Key Laboratory for Neurodegenerative Disease of The Ministry of Education, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yue Teng
authors.initials: YT
authors.lastname: Wei
authors.forename: Zhao Hui
authors.initials: ZH
authors.lastname: Zu
authors.forename: Rong Kai
authors.initials: RK
authors.lastname: Ju
authors.forename: Mu Yao
authors.initials: MY
authors.lastname: Guo
authors.forename: Xiu Mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Qun Yuan
authors.initials: QY
authors.lastname: Xu
authors.forename: Fu Zhai
authors.initials: FZ
authors.lastname: Cui
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
chemical_list: D001672:Biocompatible Materials; D019208:Brain-Derived Neurotrophic Factor; D003692:Delayed-Action Preparations; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid