In vitro and in vivo evaluation of acellular diaphragmatic matrices seeded with muscle precursors cells and coated with VEGF silica gels to repair muscle defect of the diaphragm.
In this work, a bioartificial system consisting of VEGF-loaded porous silica gel and myoblasts cultured on acellular diaphragmatic matrix (ADM) has been implanted to repair a surgically created diaphragmatic defect in Lewis rats. ADMs exerted a strong angiogenic response on chorio-allantoic membrane. Cytotoxicity, VEGF release and matrix erodibility in vitro tests demonstrated that the silica support was nontoxic and that the VEGF bioactivity was maintained after matrix entrapment and it was released within a timeframe that can be modulated by synthesis parameters. Different grafts composed by ADMs with and without autologous male myoblasts or/and VEGF-loaded porous silica gel have been implanted to repair previously created diaphragmatic defects in female Lewis rats. Patches composed of ADMs and myoblasts appeared well preserved until 8 weeks, and contained multinucleated cells and cholinergic fibers. At 8 weeks, the implanted cells were still present inside the patches. The disappointing results obtained when VEGF was delivered by porous silica gel were probably due to an abnormal angiogenic response following an excess of local growth factor concentration. Taken together, these results confirmed that our matrices contained biologically active angiogenic factors which were per se sufficient to induce neo-vessels formation, thus allowing the survival of implanted myoblasts.
Conconi
Maria T
MT
Department of Pharmaceutical Sciences, University of Padua, Padua, Italy.
Bellini
Silvia
S
Teoli
Debora
D
de Coppi
Paolo
P
Ribatti
Domenico
D
Nico
Beatrice
B
Simonato
Enea
E
Gamba
Pier G
PG
Nussdorfer
Gastone G
GG
Morpurgo
Margherita
M
Parnigotto
Pier P
PP
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D003964:Diaphragm / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005782:Gels; D006801:Humans; D020007:Implants, Experimental; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects / Q000637:transplantation / Q000648:ultrastructure; D016062:Porosity / Q000187:drug effects; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D005782:Gels; D042461:Vascular Endothelial Growth Factor A; D012822:Silicon Dioxide