RESUMO
The 45S5-bioactive glass (BG) composition is the most commonly investigated amongst BG-based bone substitutes. By changing BG compositions and by addition of therapeutically active ions such as boron, the biological features of BGs can be tailored towards specific needs and possible drawbacks can be overcome. The borosilicate glass 0106-B1 (composition in wt%: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3) has demonstrated pro-angiogenic properties. However, the osteogenic performance of the 0106-B1-BG and its influence on cell viability and proliferation in vitro as well as its osteogenic and angiogenic properties in vivo have not been investigated. Therefore, in this study, the impact of 0106-B1-BG and 45S5-BG on osteogenic differentiation, viability and proliferation on human mesenchymal stromal cells (MSCs) was assessed in vitro. Furthermore, MSC-seeded scaffolds made from both BG types were implanted subcutaneously in immunodeficient mice for 10 weeks. Osteoid formation was quantified by histomorphometry, vascularization was visualized by immunohistological staining. Additionally, the in vivo expression patterns of genes correlating with osteogenesis and angiogenesis were analyzed. In vitro, the impact of 45S5-BG and 0106-B1-BG on the proliferation, viability and osteogenic differentiation of MSCs was comparable. In vivo, scaffolds made from 0106-B1-BG significantly outperformed the 45S5-BG-based scaffolds regarding the amount and maturation of the osteoid. Furthermore, 0106-B1-BG-based scaffolds showed significantly increased angiogenic gene expression patterns. In conclusion, the beneficial angiogenic properties of 0106-B1-BG result in improved osteogenic properties in vivo, making the 0106-B1-BG a promising candidate for further investigation, e.g. in a bone defect model.
Assuntos
Indutores da Angiogênese/administração & dosagem , Substitutos Ósseos/administração & dosagem , Boro/química , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Cerâmica/química , Regulação da Expressão Gênica/efeitos dos fármacos , Vidro , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Modelos AnimaisRESUMO
The design and development of antisense oligonucleotides and ribozymes for the treatment of diseases arising from genetic abnormalities has become a real possibility over the past few years. Improvements in oligonucleotide chemistry have led to the synthesis of nucleic acids that are relatively stable in the biological milieu. However, advances in cellular targeting and intracellular delivery will probably lead to more widespread clinical applications. This review looks at recent advances in the in vitro and in vivo delivery of antisense oligodeoxynucleotides and ribozymes.
RESUMO
Antisense oligonucleotides, ribozymes and DNAzymes have emerged as novel, highly selective inhibitors or modulators of gene expression. Indeed, their use in the treatment of diseases arising from genetic abnormalities has become a real possibility over the past few years. The first antisense drug molecule is now available for clinical use in Europe and USA. However, their successful application in the clinic will require improvements in cellular targeting and intracellular delivery. This review aims to look at recent advances in the in vitro and in vivo delivery of antisense oligodeoxynucleotides and ribozymes.
