Development of a Biomaterial Scaffold Integrated with Osteoinductive Oxysterol Liposomes to Enhance Hedgehog Signaling and Bone Repair
Autor: | Takashi Sono, Min Lee, Chung-Sung Lee, Aaron W. James, Ginny Ching Yun Hsu |
---|---|
Rok vydání: | 2021 |
Předmět: |
Male
Stromal cell Bone Regeneration Pharmaceutical Science 02 engineering and technology Bone healing Thiophenes Cholesterol analog 030226 pharmacology & pharmacy 03 medical and health sciences Mice 0302 clinical medicine Osteogenesis Apatites Drug Discovery medicine Animals Humans Hedgehog Proteins Bone regeneration Endochondral ossification Cyclohexylamines Bone Transplantation Tissue Scaffolds Chemistry Skull Cell Differentiation Mesenchymal Stem Cells Oxysterols X-Ray Microtomography 021001 nanoscience & nanotechnology Hedgehog signaling pathway Cell biology Disease Models Animal medicine.anatomical_structure Liposomes Molecular Medicine Female Bone marrow 0210 nano-technology Smoothened Signal Transduction |
Zdroj: | Molecular pharmaceutics. 18(4) |
ISSN: | 1543-8392 |
Popis: | Bone repair requires the tightly regulated control of multiple intrinsic and extrinsic cell types and signaling pathways. One of the positive regulatory signaling pathways in membranous and endochondral bone healing is the Hedgehog (Hh) signaling family. Here, a novel therapeutic liposomal delivery vector was developed by self-assembly of an Hh-activating cholesterol analog with an emulsifier, along with the addition of Smoothened agonist (SAG) as a drug cargo, for the enhancement of Hh signaling in bone regeneration. The drug-loaded nanoparticulate agonists of Hh signaling were immobilized onto trabecular bone-mimetic apatite-coated 3D scaffolds using bioinspired polydopamine adhesives to ensure favorable microenvironments for cell growth and local therapeutic delivery. Results showed that SAG-loaded liposomes induced a significant and dose-dependent increase in Hh-mediated osteogenic differentiation, as evidenced by in vitro analysis of bone marrow stromal cells, and in vivo calvarial bone healing, as evidenced using all radiographic parameters and histomorphometric analyses. Moreover, favorable outcomes were achieved in comparison to standards of care, including collagen sponge-delivered rBMP2 or allograft bone. In summary, this study demonstrates using a nanoparticle packaged Hh small molecule as a widely applicable bone graft substitute for robust bone repair. |
Databáze: | OpenAIRE |
Externí odkaz: |