title: In situ controlled release of rhBMP-2 in gelatin-coated 3D porous poly(ε-caprolactone) scaffolds for homogeneous bone tissue formation.
abstract: In tissue engineering, incorporation of bone morphogenetic protein-2 (BMP-2) into biomaterial scaffolds is an attractive strategy to stimulate bone repair. However, suboptimal release of BMP-2 remains a great concern, which may cause unfavorable bone formation as well as severe inflammation. In this study, genipin-cross-linked gelatin entrapped with recombinant human BMP-2 (rhBMP-2) was exploited to decorate the interior surface of three-dimensional porous poly(ε-caprolactone) (PCL) scaffolds. With gelatin-coating, PCL scaffolds demonstrated enhanced water uptake and improved compressive moduli. Intriguingly, a unique release profile of rhBMP-2 composed of a transient burst release followed by a sustained release was achieved in coated scaffolds. These coated scaffolds well supported growth and osteogenesis of human mesenchymal stem cells (hMSCs) in vitro, indicating the retaining of rhBMP-2 bioactivity. When hMSCs-seeded scaffolds were implanted subcutaneously in nude mice for 4 weeks, better bone formation was observed in gelatin/rhBMP-2-coated scaffolds. Specifically, the spatial distribution of newly formed bone was more uniform in gelatin-coated scaffolds than in uncoated scaffolds, which displayed preferential bone formation at the periphery. These results collectively demonstrated that gelatin-coating of porous PCL scaffolds is a promising approach for delivering rhBMP-2 to stimulate improved bone regeneration.
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering and ‡State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Tan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Ye
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Tan
authors.forename: Meidong
authors.initials: M
authors.lastname: Lang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000737:chemistry*; D002417:Cattle; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D011091:Polyesters; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C016240:polycaprolactone; D005780:Gelatin