title: Poly-L-lactide acid-modified scaffolds for osteoinduction and osteoconduction.
abstract: Poly-L-lactide acid (PLLA) scaffold has been modified to enhance its osteoconductive and osteoinductive properties in view of a bone tissue engineering application. Two approaches have been followed: (i) coating with laminin or fibronectin and (ii) grafting with arginine-glycine-aspatic acid (RGD) or SIKVAV peptides. Moreover we have added a bioactive molecule 1,25-(OH)₂ D3 into the scaffold that shows better cellular interaction to implement osteoinduction and osteogenesis. The two coatings promoted only cell adhesion in the very short term while even if grafted scaffolds had cell seeding efficiency similar to ungrafted PLLA, the grafted ones supported better the proliferation of seeded human osteoblast (hOB) and human mesenchymal stem cells (hMSCs) over 1 week of culture. Our data showed that in view of bone integration and bone regeneration, PLLA grafting with RGD can be considered a good substrate to induce hOB adhesion and proliferation but having no significant effect on the osteogenic induction, the scaffold has to be reinforced with osteoinductive molecules. It can be concluded from reverse transcriptase polymerase chain reaction results, alkaline phosphatase activity and mineralization assays that 1,25(OH)₂ D3 reinforced RGD-PLLA keeps increased cell proliferation supported by an upregulation of the studied osteogenic markers and induced hMSCs differentiation into osteoblasts demonstrating osteoinductivity and osteoconductivity of the new formulated scaffold. These results can lead to a future application of RGD-D3-PLLA as an osteogenic material for bone replacement..
authors.affiliation: Dipartimento di Scienze del Farmaco, University of Eastern Piedmont, Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bosetti
authors.forename: L
authors.initials: L
authors.lastname: Fusaro
authors.forename: E
authors.initials: E
authors.lastname: Nicolì
authors.forename: A
authors.initials: A
authors.lastname: Borrone
authors.forename: S
authors.initials: S
authors.lastname: Aprile
authors.forename: M
authors.initials: M
authors.lastname: Cannas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013718:Tensile Strength / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D011091:Polyesters; D012710:Serum Albumin, Bovine; C033616:poly(lactide)
keywords: PLLA; bone tissue engineering; calcitriol; human mesenchymal stem cells; human osteoblasts