title: Sustained delivery of recombinant human bone morphogenetic protein-2 from perlecan domain I - functionalized electrospun poly (ε-caprolactone) scaffolds for bone regeneration.
abstract: BACKGROUND
  Biomaterial scaffolds that deliver growth factors such as recombinant human bone morphogenetic proteins-2 (rhBMP-2) have improved clinical bone tissue engineering by enhancing bone tissue regeneration. This approach could be further improved if the controlled delivery of bioactive rhBMP-2 were sustained throughout the duration of osteogenesis from fibrous scaffolds that provide control over dose and bioactivity of rhBMP-2. In nature, heparan sulfate attached to core proteoglycans serves as the co-receptor that delivers growth factors to support tissue morphogenesis.
  
  
  METHODS
  To mimic this behavior, we conjugated heparan sulfate decorated recombinant domain I of perlecan/HSPG2 onto an electrospun poly(ε-caprolactone) (PCL) scaffold, hypothesizing that the heparan sulfate chains will enhance rhBMP-2 loading onto the scaffold and preserve delivered rhBMP-2 bioactivity.
  
  
  RESULTS
  In this study, we demonstrated that covalently conjugated perlecan domain I increased loading capacity of rhBMP-2 onto PCL scaffolds when compared to control unconjugated scaffolds. Additionally, rhBMP-2 released from the modified scaffolds enhanced alkaline phosphatase activity in W20-17 mouse bone marrow stromal cells, indicating the preservation of rhBMP-2 bioactivity indicative of osteogenesis.
  
  
  CONCLUSIONS
  We conclude that this platform provides a sophisticated and efficient approach to deliver bioactive rhBMP-2 for bone tissue regeneration applications.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, 2212 Jeong H. Kim Building, College Park, MD, 20742, USA. ychiu1@umd.edu.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Eliza L
authors.initials: EL
authors.lastname: Fong
authors.affiliation: Department of BioSciences, Rice University, 6500 Main Street, Houston, TX, 77030, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Grindel
authors.affiliation: Department of Orthodontics, The University of Texas Health Science Center at Houston, 7500 Cambridge St, Houston, TX, 77054, USA.
authors.forename: Fred K
authors.initials: FK
authors.lastname: Kasper
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX, 77030, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Harrington
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX, 77030, USA.|Department of BioSciences, Rice University, 6500 Main Street, Houston, TX, 77030, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
keywords: Alkaline phosphatase; Bone morphogenetic protein; Bone regeneration; Heparan sulfate; Perlecan/HSPG2; Poly(ε-caprolactone)