Synthesis and Biological Evaluation of Cell Affinitive Oligo(poly(ethylene glycol) fumarate)-Gelatin Methacrylate (OPF-GELMA) Interpenetrating Network Hydrogels.

Hybrid hydrogels that integrate mechanical tunability with biological activity are critical for regenerative medicine. Oligo(poly(ethylene glycol) fumarate) (OPF) offers controllable network formation but lacks intrinsic cell affinity. Here, we incorporated gelatin methacrylate (GelMA) into OPF networks to develop an interpenetrating network (IPN) hybrid OPF-GELMA hydrogel that combines the mechanical versatility of OPF with the bioactivity of GelMA. The crosslinked hydrogels with varying GelMA content exhibited GelMA-dependent modulation of swelling, gel fraction, compressive stiffness, and microstructure. Increasing GelMA concentration reduced water uptake while significantly enhancing mechanical strength and proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Moreover, GelMA incorporation markedly enhanced rBMSC osteogenic differentiation, as demonstrated by elevated alkaline phosphatase activity and increased Runx2 expression. These results demonstrate that OPF-GELMA hydrogels enable synergistic regulation of biochemical and mechanical cues, providing a versatile scaffold platform for bone tissue engineering and regenerative medicine applications.