Substance P/dexamethasone-encapsulated PLGA scaffold fabricated using supercritical fluid process for calvarial bone regeneration.

Poly(lactic-co-glycolic acid) (PLGA) scaffolds encapsulated with substance P (SP) and dexamethasone (Dex) by the supercritical CO2 foaming method were fabricated to treat calvarial bone. We compared the release profiles of SP and Dex according to the incorporation methods using encapsulation or dipping. Ninety percent of the SP or Dex molecules in the scaffolds prepared by the encapsulating method were released by day 14 or day 6, respectively. In vivo real-time assays for human mesenchymal stem cell (hMSC) tracking were performed to confirm the MSC recruitment abilities of the scaffolds. The results showed that the optical intensity of the SP-encapsulated group was 2.59 times higher than that of the phosphate-buffered saline group and 1.3 times higher than that of the SP-dipping group. Furthermore, we compared the angiogenesis activity of the scaffolds. In the SP-encapsulated group, 72.9  ±  2.6% of the vessels showed matured features by 1 week, and it increased to 82.0  ±  4.6% after 4 weeks. We implanted the scaffolds into rat calvarial defects. After 24 weeks, SP- and Dex-encapsulated scaffolds showed 67.1% and 26.2% higher bone formation than those of the Dex-encapsulated group and SP-encapsulated group, respectively, and they formed 36.1% more bone volume compared with the SP- and Dex-dipped scaffolds. Consequently, the results of this study suggest that SP- and Dex-encapsulated scaffolds made by the supercritical CO2 foaming method could be a good treatment modality to treat critical bone defects without cell transplantation by recruiting autologous stem cells and forming new bone tissues.