title: Resveratrol-conjugated poly-ε-caprolactone facilitates in vitro mineralization and in vivo bone regeneration.
abstract: Incorporation of osteoinductive factors in a suitable scaffold is considered a promising strategy for generating osteogenic biomaterials. Resveratrol is a polyphenol found in parts of certain plants, including nuts, berries and grapes. It is known to increase DNA synthesis and alkaline phosphatase (ALP) activity in osteoblasts and to prevent femoral bone loss in ovariectomized (OVX) rats. In the present study resveratrol was coupled through a hydrolysable covalent bond with the carboxylic acid groups in porous poly-ε-caprolactone (PCL) surface grafted with acrylic acid (AA). The osteogenic effect of this new scaffold was evaluated in mesenchymal cell culture and in the rat calvarial defect model. We found that the incorporation of resveratrol caused increased ALP activity of rat bone marrow stromal cells and enhanced mineralization of the cell-scaffold composites in vitro. After 8 weeks the calvarial defects implanted with resveratrol-conjugated PCL displayed a higher X-ray density than the defects implanted with control PCL. Bone-like structures, positively immunostained for bone sialoprotein, were shown to be more extensively formed in the resveratrol-conjugated PCL. These results show that incorporation of resveratrol into the AA-functionalized porous PCL scaffold led to a significant increase in osteogenesis.
authors.affiliation: Department for Clinical Science, Intervention and Technology, Division of Orthopedics, Karolinska Institute, Stockholm, Sweden. yan.li@ki.se
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Staffan
authors.initials: S
authors.lastname: Dånmark
authors.forename: Ulrica
authors.initials: U
authors.lastname: Edlund
authors.forename: Anna
authors.initials: A
authors.lastname: Finne-Wistrand
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.forename: Maria
authors.initials: M
authors.lastname: Norgård
authors.forename: Eva
authors.initials: E
authors.lastname: Blomén
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.forename: Urban
authors.initials: U
authors.lastname: Lindgren
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D019919:Prosthesis Implantation; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D017550:Spectroscopy, Fourier Transform Infrared; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000179:Acrylates; D011091:Polyesters; D013267:Stilbenes; C016240:polycaprolactone; D000469:Alkaline Phosphatase; C036658:acrylic acid; D000077185:Resveratrol