Integrated experimental and bioinformatics analysis reveals ECM-integrin and redox signaling associated with PMMA/NiO...

Poly(methyl methacrylate) (PMMA) is widely used in dental and craniofacial applications; however, its clinical performance is limited by poor surface wettability, moderate mechanical strength, and restricted biological activity. Integrating nanomaterial engineering with computational biology offers an opportunity to better understand biomaterial-cell interactions and support the rational design of functional biomaterials.

Nickel oxide (NiO) nanoparticles were synthesized via chemical precipitation and incorporated into PMMA to fabricate nanocomposites. Physicochemical characterization included contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Vickers hardness testing. Biocompatibility was evaluated using zebrafish embryo developmental assays. To explore biological processes potentially associated with biomaterial-cell interactions, bioinformatics analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING protein-protein interaction (PPI) network analyses were performed.

Incorporation of NiO nanoparticles improved the surface and mechanical properties of PMMA, reducing the contact angle from 105.35° to 90.46° and increasing Vickers hardness compared with unmodified PMMA. Structural and morphological analyses confirmed successful synthesis and homogeneous nanoparticle incorporation. Zebrafish embryo studies demonstrated minimal developmental toxicity, supporting the biocompatibility of the nanocomposite. Bioinformatics analyses identified significant enrichment of pathways related to extracellular matrix organization, cell adhesion, focal adhesion, PI3K-Akt signaling, and oxidative stress regulation. Protein-protein interaction analysis revealed highly interconnected networks associated with ECM-integrin signaling and redox homeostasis, highlighting biological processes potentially associated with biomaterial-cell communication.

PMMA/NiO nanocomposites exhibited improved physicochemical performance and favorable biocompatibility characteristics. The integration of experimental characterization with bioinformatics and network-based analyses provides a systems-level perspective on biomaterial-associated cellular processes and identifies ECM-integrin signaling and oxidative stress-related pathways as candidate biological processes for future experimental validation. These findings support the continued development of PMMA/NiO nanocomposites for oral and craniofacial biomedical applications.