Abstract
Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca and Sr ions was investigated. MOFs were generated by choosing osteoinductive Ca and Sr metals, and an organic ligand 1,3,5 tricarboxylicbenzene (H3BTC) as a linker. These MOFs were able to induce in vitro biomineralization from pre-osteoblastic MC3T3 cells and human mesenchymal stem cells (hMSCs). Moreover, these MOFs (when loaded with dimethyloxalylglycine (DMOG)) induced vascular endothelial production from hMSCs. qRT-PCR analysis performed on hMSCs (isolated from femoral heads of patients undergoing joint arthroplasty) treated with MOFs crystals suggested that the CaSr-MOFs by themselves can upregulate osteogenic genes in hMSCs, which is the first time to our knowledge that this has been observed from MOFs.
Highlights
Hydroxyapatite remains the state-of-the-art material for osteogenesis because of its ability to provide a large reservoir of Ca for bone mineralization[1]
We were able to show that a small molecule drug dimethyloxalylglycine (DMOG), which is a prolyl hydroxylase (PHD) pathway inhibitor and involved in bone regeneration, can be loaded into the Metal-organic frameworks (MOFs)
Room temperature synthesis was chosen as that would preserve the activity of drugs that could potentially be encapsulated in the future
Summary
Received: 16 May 2019 Accepted: 23 August 2019 Published: xx xx xxxx applications. Naomi Joseph[1], Harrison D. We were able to show that a small molecule drug dimethyloxalylglycine (DMOG), which is a prolyl hydroxylase (PHD) pathway inhibitor and involved in bone regeneration, can be loaded into the MOFs. we were able to show that a small molecule drug dimethyloxalylglycine (DMOG), which is a prolyl hydroxylase (PHD) pathway inhibitor and involved in bone regeneration, can be loaded into the MOFs Using this new material, we performed a series of in vitro tests, including bone mineralization deposit assays, alkaline phosphatase production, and qRT-PCR-based analysis of osteogenic gene expression in pre-osteoblasts and human mesenchymal stem cells. 1 ml of H3BTC solution was added to the salt solution and gently stirred This solution was allowed to sit at room temperature for 3 days for MOF crystallization, washed and dried (as described in the previous paragraph).
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