Abstract:
:There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release platform for bone repair.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Smith EL,Kanczler JM,Gothard D,Roberts CA,Wells JA,White LJ,Qutachi O,Sawkins MJ,Peto H,Rashidi H,Rojo L,Stevens MM,El Haj AJ,Rose FR,Shakesheff KM,Oreffo ROdoi
10.1016/j.actbio.2014.05.025subject
Has Abstractpub_date
2014-10-01 00:00:00pages
4197-205issue
10eissn
1742-7061issn
1878-7568pii
S1742-7061(14)00237-2journal_volume
10pub_type
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pub_type: 杂志文章
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doi:10.1016/j.actbio.2017.01.003
更新日期:2017-03-01 00:00:00
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