Evaluation of skeletal tissue repair, part 1: assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model.
Current clinical treatments for skeletal conditions resulting in large-scale bone loss include autograft or allograft, both of which have limited effectiveness. In seeking to address bone regeneration, several tissue engineering strategies have come to the fore, including the development of growth factor releasing technologies and appropriate animal models to evaluate repair. Ex vivo models represent a promising alternative to simple in vitro systems or complex, ethically challenging in vivo models. We have developed an ex vivo culture system of whole embryonic chick femora, adapted in this study as a critical size defect model to investigate the effects of novel bone extracellular matrix (bECM) hydrogel scaffolds containing spatio-temporal growth factor-releasing microparticles and skeletal stem cells on bone regeneration, to develop a viable alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-β3 or BMP-2 were placed, with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF or HSA/TGF-β3 demonstrated a cartilage-like phenotype, with minimal collagen I deposition, comparable to HSA-only control hydrogels. The addition of BMP-2 releasing microparticles resulted in enhanced structured bone matrix formation, evidenced by increased Sirius red-stained matrix and collagen expression within hydrogels. This study demonstrates delivery of bioactive growth factors from a novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of an organotypic chick femur defect culture system as a high-throughput test model for scaffold/cell/growth factor therapies for regenerative medicine.
['Smith|E L|EL|', 'Kanczler|J M|JM|', 'Gothard|D|D|', 'Roberts|C A|CA|', 'Wells|J A|JA|', 'White|L J|LJ|', 'Qutachi|O|O|', 'Sawkins|M J|MJ|', 'Peto|H|H|', 'Rashidi|H|H|', 'Rojo|L|L|', 'Stevens|M M|MM|', 'El Haj|A J|AJ|', 'Rose|F R A J|FR|', 'Shakesheff|K M|KM|', 'Oreffo|R O C|RO|']
D000328:Adult D000464:Alginates D000818:Animals D001854:Bone Marrow Cells D001861:Bone Regeneration D002417:Cattle D002645:Chickens D005109:Extracellular Matrix D005269:Femur D020723:Glucuronic Acid D006603:Hexuronic Acids D006801:Humans D020100:Hydrogels D036341:Intercellular Signaling Peptides and Proteins D032496:Satellite Cells, Skeletal Muscle D017154:Stromal Cells
Ex vivo model Bioactive growth factor delivery Bone repair ECM hydrogel scaffolds Embryonic femur