Enhanced Osteogenic Differentiation of hMSCs Using BMP@ZIF-8-Loaded GelMA Nanocomposite Hydrogels with Controlled
Weihao Yuan1, Luiza de Almeida Queiroz Ferreira1,2, Ronit Khade1
1Weintraub Center for Reconstructive Biotechnology, Section of Prosthodontics, School of Dentistry, University of California, Los Angeles, California 90095, United States.
Abstract:
Hydrogels are highly versatile materials with immense potential for tissue engineering and regenerative medicine owing to their biocompatibility, tunable mechanical properties, and ability to mimic the natural extracellular matrix. Their 3D porous structure allows for the encapsulation and delivery of bioactive molecules, making them ideal candidates for drug delivery systems. In tissue repair, particularly for bone regeneration, hydrogels can serve as carriers that release therapeutic agents in a controlled manner, thus enhancing the healing process. Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles and recombinant human Bone Morphogenetic Protein (rhBMP-2) molecules were incorporated solely (ZIF@GelMA) or in association (BMP@ZIF@GelMA) into gelatin modified by a methacryloyl hydrogel (GelMA) to investigate its physical and osteogenic properties. Hydrogels were characterized by Scanning Electron Microscopy and rheological tests. We analyzed hydrogel degradation and the BSA release profile of BMP@ZIF@GelMA samples throughout 0, 1, 3, 7, 14, and 28 days. Cell adhesion and bone formation markers were analyzed for hydrogel-encapsulated human dental pulp cells by using immunocytochemistry and molecular analysis. ZIF@GelMA and BMP@ZIF@GelMA exhibited a porous and viscoelastic structure with increased storage modulus when rhBMP2 was present. BSA@ZIF@GelMA showed a balanced degradation rate and a controlled release of BSA. The ZIF@GelMA upregulated the expression of cell adhesion and bone formation genes, and when BMP-2 was introduced, the levels of markers were remarkably elevated. BMP@ZIF@GelMA hydrogel presents several favorable factors to promote cellular adhesion and bone regeneration, thus encouraging further prospects for advanced therapeutic applications in tissue repair.
