Novel osteoinductive biomimetic scaffolds stimulate human osteoprogenitor activity--implications for skeletal repair.
The development of new bone formation strategies offers tremendous therapeutic implications in a variety of musculoskeletal diseases. One approach involves harnessing the regenerative capacity of osteoprogenitor bone cells in combination with biomimetic scaffolds generated from appropriate scaffold matrices and osteoinductive factors. The aims of our study were to test the efficacy of two innovative osteoinductive agents: the osteoblast stimulating factor-1 (osf-1), an extracellular matrix-associated protein, and osteoinductive extracts of Saos-2 cells on human osteoprogenitor cells. Saos-2 extracted osteoinductive factors significantly stimulated alkaline phosphatase specific activity in basal and osteogenic conditions. Osf-1 significantly stimulated chemotaxis, total colony formation, alkaline phosphatase-positive colony formation, and alkaline phosphatase specific activity at concentrations as low as 10 pg/ml compared with control cultures. Osteoinductive factors present in Saos-2 cell extracts and osf-1 promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on 3-D scaffolds. The successful generation of 3-D biomimetic structures incorporating osf-1 or osteoinductive factors from Saos-2 cells indicates their potential for de novo bone formation that exploits cell-matrix interactions.
Yang
X B
XB
University Orthopaedics, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Green
D W
DW
Roach
H I
HI
Clarke
N M P
NM
Anderson
H C
HC
Howdle
S M
SM
Shakesheff
K M
KM
Oreffo
R O C
RO
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials; D001854:Bone Marrow Cells; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D023822:Tissue Engineering
D001672:Biocompatible Materials; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D011108:Polymers; C066845:pleiotrophin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase