Multifunctional methacrylated gelatin-hyaluronic acid-psoralen hydrogel for bone defect repair: Synergistic anti-inflammatory, ROS-scavenging, and osteoinductive effects

Sep 24, 2025International journal of biological macromolecules

Gelatin-hyaluronic acid hydrogel with psoralen for bone repair: Combined anti-inflammatory, antioxidant, and bone-growing effects

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Abstract

An injectable, photocurable composite hydrogel, GelMA-HA-PSO, shows potential for minimally invasive bone defect repair.

GelMA-HA-PSO hydrogel is composed of methacrylated gelatin, hyaluronic acid, and psoralen.
The hydrogel's exceptional injectability allows it to adapt to complex bone defect geometries.
In vitro studies indicate the hydrogel exhibits biocompatibility and reduces reactive oxygen species levels.
It suppresses pro-inflammatory cytokine expression in macrophages, suggesting anti-inflammatory properties.
Enhanced alkaline phosphatase activity and upregulation of osteogenesis-related genes indicate osteogenic potential.
The incorporation of hyaluronic acid improves the hydrogel's mechanical properties and swelling capacity.

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Bone defects arising from trauma, tumors, or infections pose clinical challenges, primarily due to the limitations of current biofiller materials, which often fail to conform to irregular defect geometries and mitigate post-surgical complications such as inflammation and oxidative stress. To address these issues, we developed an injectable, photocurable composite hydrogel, GelMA-HA-PSO, which is composed of methacrylated gelatin (GelMA), hyaluronic acid (HA), and psoralen (PSO). A key highlight of our design is its minimally invasive potential, enabled by the hydrogel's exceptional injectability and in situ photo-crosslinkable properties. This unique combination allows the hydrogel to seamlessly adapt to complex and irregular bone defects during clinical procedures, offering a significant advantage over traditional materials. The injectable nature of GelMA-HA-PSO facilitates precise delivery to the defect site, while its photocuring capability ensures rapid and stable fixation in place, minimizing the need for extensive surgical intervention. Beyond its engineering advantages, the GelMA-HA-PSO hydrogel exhibits multifunctional therapeutic properties, including anti-inflammatory, antioxidant, and osteogenic effects. In vitro studies have demonstrated its biocompatibility and efficacy in reducing reactive oxygen species levels in MC3T3-E1 cells, as well as suppressing pro-inflammatory cytokine expression in RAW264.7 macrophages. Its osteogenic potential was further confirmed through enhanced alkaline phosphatase activity and upregulation of osteogenesis-related genes and proteins. Immunofluorescence analysis validated its capacity to modulate inflammatory markers and promote osteogenic differentiation. The incorporation of HA enhanced the hydrogel's storage modulus and swelling properties, while PSO facilitated sustained drug release and improved its bioactivity. Collectively, this study demonstrates the development and validation of a multifunctional GelMA/HA/PSO hydrogel that integrates biological (antioxidant, anti-inflammatory, osteogenic) and engineering (injectable, photo-crosslinkable) properties, with a particular emphasis on its minimally invasive potential for bone defect repair.

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