Physical and Osteogenic Properties of ZIF Nanoparticles-Containing Hydrogel Delivery System

Objectives: Here, we aimed to incorporate Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles and Bone Morphogenetic Protein (BMP-2) molecules into gelatin modified by methacryloyl hydrogel (GelMA) and investigate its physical properties and ability towards osteogenesis.
Methods: ZIF-8 nanoparticles were synthesized and incorporated solely into GelMA hydrogel (ZIF@GelMA) or in association with BMP-2 molecules (BMP@ZIF@GelMA). The control group consisted of only GelMA. All hydrogels were characterized by Scanning Electron Microscopy (SEM), rheological analysis, and compressive strength. The degradation ratio and BSA release of BMP@ZIF@GelMA were analyzed throughout the following time points: 0, 1, 3, 7, 14, and 28. Human Mesenchymal Stem Cells (hMSCs) were encapsulated into all hydrogels, and samples were collected for immunofluorescence staining of Integrin b-1 and Osteocalcin. We used q-PCR to analyze the regulation of MAPK, Alkaline Phosphatase, Collagen Type I, Osteocalcin, and Runt-Related Transcription Factor 2 after cell encapsulation.
Results: SEM characterization showed that ZIF@GelMA and BMP@ZIF@GelMA exhibited a porous structure resembling GelMA. The modified hydrogels have consistent viscoelastic characteristics, while BMP@ZIF@GelMA revealed a slightly elevated elastic mode and is more resistant to deformation when compared to the other groups. BSA@ZIF@GelMA showed a balanced degradation rate and a sustained and controlled release of BSA, with the release percentage gradually increasing as time progressed. The ZIF@GelMA upregulated the expression of Integrin b-1 and Osteocalcin, and when BMP-2 was introduced into the hydrogel, the expression levels of the markers were elevated. While within the BMP@ZIF@GelMA hydrogel, there was a pronounced expression of several pivotal genes integral to bone formation and cellular adhesion.
Conclusions: In the comprehensive analysis of BMP@ZIF@GelMA hydrogel, several key findings emerged that underscore its potential in bone regeneration and cellular adhesion, offering exciting prospects for advanced therapeutic applications, particularly in the realm of bone regeneration and cellular adhesion, warranting further exploration and clinical trials.