title: The application of human bone marrow stromal cells and poly(dl-lactic acid) as a biological bone graft extender in impaction bone grafting.
abstract: Concerns over disease transmission, high costs and limited supply have led to interest in synthetic grafts in the field of impaction bone grafting (IBG). Poly(DL-lactic acid) (PLA) grafts are attractive alternatives due to their biocompatibility, established safety and versatile manufacturing process. This study examined the potential of PLA scaffolds augmented with human bone marrow stromal cells (HBMSCs) in IBG. In vitro and in vivo studies were performed on impacted morsellised PLA seeded with HBMSC and compared to PLA alone. In vitro samples were incubated under osteogenic conditions and in vivo samples were implanted subcutaneously into severely compromised immunodeficient mice, for 4 weeks. Biochemical, histological, mechanical and 3D micro-computed tomography analyses were performed. HBMSC viability, biochemical activity and histological evidence of osteogenic cellular differentiation, post-impaction were observed in vitro and in vivo in PLA/HBMSC samples compared to impacted PLA alone. In vitro PLA/HBMSC samples demonstrated evidence of mechanical enhancement over PLA alone. In vivo studies showed a significant increase in new bone and blood vessel formation in the PLA/HBMSC constructs compared to PLA alone. With alternatives to allograft being sought, these studies have demonstrated PLA/HBMSC living composites, to be a potential prospect as a biological bone graft extender for future use in the field of IBG.
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD, UK. bbolland@btinternet.com
authors.forename: Benjamin J R F
authors.initials: BJ
authors.lastname: Bolland
authors.forename: Janos M
authors.initials: JM
authors.lastname: Kanczler
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Ginty
authors.forename: Steve M
authors.initials: SM
authors.lastname: Howdle
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Dunlop
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011091:Polyesters / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D033081:Shear Strength; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D000469:Alkaline Phosphatase