2D Covalent Organic Framework Direct Osteogenic Differentiation of Stem Cells

Abstract

2D covalent organic frameworks (COFs) are an emerging class of crystalline porous organic polymers with a wide-range of potential applications. However, poor processability, aqueous instability, and low water dispersibility greatly limit their practical biomedical implementation. Herein, a new class of hydrolytically stable 2D COFs for sustained delivery of drugs to direct stem cell fate is reported. Specifically, a boronate-based COF (COF-5) is stabilized using amphiphilic polymer Pluronic F127 (PLU) to produce COF-PLU nanoparticles with thickness of ≈25 nm and diameter ≈200 nm. These nanoparticles are internalized via clathrin-mediated endocytosis and have high cytocompatibility (half-inhibitory concentration ≈1 mg mL −1 ). Interestingly, the 2D COFs induce osteogenic differentiation in human mesenchymal stem cells, which is unique. In addition, an osteogenic agent-dexamethasone-is able to be loaded within the porous structure of COFs for sustained delivery which further enhances the osteoinductive ability. These results demonstrate for the first time the fabrication of hydrolytically stable 2D COFs for sustained delivery of dexamethasone and demonstrate its osteoinductive characteristics.

Drug Delivery to the Brain: Recent Advances and Unmet Challenges

“…Nanoparticles (NPs) such as liposomes, polymeric NPs, inorganic NPs, etc., are being used as drug carriers for decades [ 80 , 81 , 82 , 83 , 84 , 85 ]. Drug loading in NPs enhances circulation life of hydrophobic drugs in blood, protect nucleic-acid-based therapeutics from serum nucleases, or reduce the adverse off-target effects of drugs [ 86 , 87 , 88 , 89 , 90 ]. Surface of NPs can be engineered with PEG to achieve longer circulation life or with cell-penetrating peptide to enhance cellular uptake [ 91 ], or with targeting ligand to selectively deliver the payloads at targeted tissue [ 92 ].…”

Covalent organic frameworks: linkage types, synthetic methods and bio-related applications

“…Bhunia et al also reported new 2D COF–polymer nanoparticles for drug delivery by combining colloidal COF-5 and an amphiphilic polymer, which was the first report demonstrating the osteoinductive ability of COFs. 218 They not only found that the 2D COF was able to induce osteogenic differentiation of hMSCs in the absence of an osteoinductive agent, but also loaded the osteoinducing agent dexamethasone within the porous structure of COFs to further enhance the osteoinductive ability, demonstrating the impressive features and great potential of COFs for wider applications.…”

Regulation of metabolic microenvironment with a nanocomposite hydrogel for improved bone fracture healing

“…Covalent organic frameworks (COFs) are emerging crystalline porous organic polymers for the sustained delivery of drugs [ 22 ]. For example, Bhunia et al fabricated a boronate-based COF loaded with dexamethasone and demonstrated that the hydrolytically stable COF nanocomposite was able to induce MSC osteogenic differentiation in the absence of an osteoinductive agent [ 23 ]. Hydrogels are widely applied in bone tissue engineering for cell adhesion and drug delivery due to their controllable mechanical properties, superior biocompatibility, and excellent drug loading capacity [ 24 , 25 ].…”