RESUMO
Our previous study reported that an osteopontin-derived peptide SVVYGLR activates the adhesion, migration and tube formation abilities of endothelial cells in vitro. The present study investigated angiogenesis due to synthetic SVVYGLR and mutant peptides in vivo. Mutant peptides (n = 7) were synthesized by substituting alanine (A) for one of the 7 amino acids comprising SVVYGLR. In dorsal air sac assay, mouse dorsal skin 5 days after implantation of a chamber filled with SVVYGLR had approximately the same number of newly formed blood vessels to that filled with vascular endothelial growth factor (VEGF). The ability of angiogenesis due to SVVAGLR was significantly lower than that due to other 6 mutant peptides and SVVYGLR. This indicates that tyrosine (Y) plays an important role in angiogenesis due to SVVYGLR.
Assuntos
Indutores da Angiogênese/farmacologia , Células Endoteliais/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Sialoglicoproteínas/farmacologia , Motivos de Aminoácidos , Substituição de Aminoácidos , Indutores da Angiogênese/química , Animais , Células Endoteliais/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Osteopontina , Sialoglicoproteínas/química , Sialoglicoproteínas/fisiologia , Tirosina/fisiologiaRESUMO
In tissue engineering, biodegradable polymer materials with both high biocompatibility and high strength are very important as scaffolds for long term use. Therefore, in this research, we tried to prepare the three types of poly(L-lactic acid) (PLLA)/calcium phosphate (CP) hybrid composite for a scaffold biomaterial. The effects of addition of different CP on both biocompatibility and mechanical properties were evaluated. CP powders and voids were three-dimensionally and uniformly distributed in the solid samples and porous composite samples. These compositions of CP and PLLA greatly improved the cellular adhesiveness, which increased as the volume fraction of CP in the composite increased. For the porous samples, cells migrated into the pores. This study demonstrated that a composite of PLLA and CP is an effective new scaffold material that results in better osteoconductivity, bone regeneration, and mineralization and has moderately high strength.
Assuntos
Implantes Absorvíveis , Regeneração Óssea , Fosfatos de Cálcio , Ácido Láctico , Osteoblastos/efeitos dos fármacos , Polímeros , Alicerces Teciduais , Células 3T3 , Animais , Bioengenharia , Fosfatos de Cálcio/síntese química , Fosfatos de Cálcio/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Ácido Láctico/síntese química , Ácido Láctico/farmacologia , Masculino , Teste de Materiais , Camundongos , Poliésteres , Polímeros/síntese química , Polímeros/farmacologia , Porosidade , Ratos , Ratos Sprague-Dawley , Engenharia TecidualRESUMO
Angiogenesis plays an important role in various pathological conditions as well as some physiological processes. Although a number of soluble angiogenic factors have been reported, extracellular matrix also has crucial effect on angiogenesis through interaction with endothelial cells. Since recent reports showed osteopontin had some angiogenic activity, the effect of the SVVYGLR peptide, novel binding motif in osteopontin molecule, on angiogenesis was examined in this study. Synthetic peptide SVVYGLR did not have proliferative effect on endothelial cells but adhesion and migration activity to endothelial cells. Furthermore, SVVYGLR had as potent activity for tube formation in three-dimensional collagen gel as vascular endothelial growth factor which is known to be the strongest angiogenic factor. Electron microscopical analysis showed a number of microvilli on the endothelial luminar surface and tight junction formation in the luminar intercellular border between endothelial cells, indicating SVVYGLR induced cell porarity and differentiation of endothelial cells. This small peptide might be expected to stimulate angiogenesis to improve some ischemic conditions in the future because of some advantages due to smaller molecular weight.