title: Smurf1 knocked-down, mesenchymal stem cells and BMP-2 in an electrospun system for bone regeneration.
abstract: A sandwich-like system, fabricated with electrospun, poly(lactic-co-glycolic-acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells (rMSC), or rMSC with their Smurf1 (SMAD ubiquitin regulatory factor-1) expression knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a rat calvarial, critical-size defect. The behavior of four membrane varieties, fabricated with different PLGA copolymers, was initially studied in rMSC cultures to decide on optimal membrane degradation and cell proliferation and differentiation characteristics. PLGA75:25 provided the most stable structure, and favored the cell environment. Radiological and histological analyses indicated bone repair in animals treated with the PLGA75:25 bioactivated systems. We found no synergist interaction between BMP-2 and rMSC 8 to 12 weeks postimplantation. By contrast, synergistic defect repair of around 85% was detected after 8 weeks of combined BMP-2 and rMSC573 treatment.
authors.affiliation: Department of Chemical Engineering and Pharmaceutical Technology, and ‡Institute of Biomedical Technologies (ITB), Center for Biomedical Research of the Canary Islands, University of La Laguna , 38200 La Laguna, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Évora
authors.forename: Emiliano
authors.initials: E
authors.lastname: García-Pizarro
authors.forename: Carlos
authors.initials: C
authors.lastname: del Rosario
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-López
authors.forename: Ricardo
authors.initials: R
authors.lastname: Reyes
authors.forename: Araceli
authors.initials: A
authors.lastname: Delgado
authors.forename: José C
authors.initials: JC
authors.lastname: Rodríguez-Rey
authors.forename: Carmen
authors.initials: C
authors.lastname: Évora
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D001861:Bone Regeneration; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002454:Cell Differentiation; D049109:Cell Proliferation; D055664:Electrochemical Techniques; D055785:Gene Knockdown Techniques; D006801:Humans; D019344:Lactic Acid; D008297:Male; D008567:Membranes, Artificial; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D055396:Bone Morphogenetic Protein 2; D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C556581:Smurf1 protein, rat; D044767:Ubiquitin-Protein Ligases