RNA interfering molecule delivery from in situ forming biodegradable hydrogels for enhancement of bone formation in rat calvarial bone defects
| Autor: | Cong Truc Huynh, Samuel Herberg, Alexandra McMillan, Phuong N. Dang, Minh Khanh Nguyen, Davood Varghai, Hooman Riazi, Eben Alsberg, Oju Jeon |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Small interfering RNA Bone Regeneration Biomedical Engineering 02 engineering and technology Bone healing Mesenchymal Stem Cell Transplantation Biochemistry Article Biomaterials 03 medical and health sciences Rats Nude Drug Delivery Systems Tissue engineering RNA interference Absorbable Implants Animals Humans RNA Small Interfering Bone regeneration Molecular Biology Chemistry Mesenchymal stem cell Skull RNA Hydrogels Mesenchymal Stem Cells General Medicine Cells Immobilized 021001 nanoscience & nanotechnology Cell biology Rats 030104 developmental biology Self-healing hydrogels Heterografts RNA Interference 0210 nano-technology Carrier Proteins Biotechnology |
| Zdroj: | Acta biomaterialia. 75 |
| ISSN: | 1878-7568 |
| Popis: | RNA interference (RNAi) may be an effective and valuable tool for promoting the growth of functional tissue, as short interfering RNA (siRNA) and microRNA (miRNA) can block the expression of genes that have negative effects on tissue regeneration. Our group has recently reported that the localized and sustained presentation of siRNA against noggin (siNoggin) and miRNA-20a from in situ forming poly(ethylene glycol) (PEG) hydrogels enhanced osteogenic differentiation of encapsulated human bone marrow-derived mesenchymal stem cells (hMSCs). Here, the capacity of the hydrogel system to accelerate bone formation in a rat calvarial bone defect model is presented. After 12 weeks post-implantation, the hydrogels containing encapsulated hMSCs and miRNA-20a resulted in more bone formation in the defects than the hydrogels containing hMSCs without siRNA or with negative control siRNA. This localized and sustained RNA interfering molecule delivery system may provide an excellent platform for healing bony defects and other tissues. Statement of Significance Delivery of RNAi molecules may be a valuable strategy to guide cell behavior for tissue engineering applications, but to date there have been no reports of a biomaterial system capable of both encapsulation of cells and controlled delivery of incorporated RNA. Here, we present PEG hydrogels that form in situ via Michael type reaction, and that permit encapsulation of hMSCs and the concomitant controlled delivery of siNoggin and/or miRNA-20a. These RNAs were chosen to suppress noggin, a BMP-2 antagonist, and/or PPAR-γ, a negative regulator of BMP-2-mediated osteogenesis, and therefore promote osteogenic differentiation of hMSCs and subsequent bone repair in critical-sized rat calvarial defects. Simultaneous delivery of hMSCs and miRNA-20a enhanced repair of these defects compared to hydrogels containing hMSCs without siRNA or with negative control siRNA. This in situ forming PEG hydrogel system offers an exciting platform for healing critical-sized bone defects by localized, controlled delivery of RNAi molecules to encapsulated hMSCs and surrounding cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect