title: Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects.
abstract: BACKGROUND
  Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM).
  
  
  METHODS
  The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5).
  
  
  RESULTS
  PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups.
  
  
  CONCLUSIONS
  Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus.
authors: Department of Orthopedics and Rheumatology, University Hospital Marburg, Marburg, Germany.
authors: Markus D
authors: MD
authors: Schofer
authors: Philip P
authors: PP
authors: Roessler
authors: Jan
authors: J
authors: Schaefer
authors: Christina
authors: C
authors: Theisen
authors: Sonja
authors: S
authors: Schlimme
authors: Johannes T
authors: JT
authors: Heverhagen
authors: Maximilian
authors: M
authors: Voelker
authors: Roland
authors: R
authors: Dersch
authors: Seema
authors: S
authors: Agarwal
authors: Susanne
authors: S
authors: Fuchs-Winkelmann
authors: Jürgen R J
authors: JR
authors: Paletta
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D004560:Electricity; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D019651:Plastic Surgery Procedures / Q000379:methods*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)