Key Takeaways & Executive Findings
- •• The EGCG-modified Cu/Zn HA/GelMA hydrogel (G-E-Cu/Zn HA) demonstrated the highest compressive stress (41.03 kPa) and prolonged degradation, indicating enhanced mechanical stability. • G-E-Cu/Zn HA exhibited superior antibacterial activity against Staphylococcus aureus and Escherichia coli compared to other groups, attributed to the synergistic effects of Cu2+/Zn2+ and EGCG. • The composite hydrogel showed excellent cytocompatibility and significantly promoted osteogenic differentiation of MC3T3-E1 cells, as evidenced by increased ALP activity, mineralization, and osteogenic gene expression. • Incorporation of Cu/Zn HA and EGCG into GelMA hydrogels effectively controlled the release of bioactive ions and EGCG, reducing burst release and providing sustained therapeutic effects.
Abstract
BACKGROUND: Hydrogel materials have garnered significant attention in tissue repair due to their good biocompatibility and degradability, but single hydrogels lack antibacterial and osteogenic functions, limiting clinical application. OBJECTIVE: To prepare hydrogels with both antibacterial and osteogenic functions for bone tissue repair. METHODS: Copper and zinc co-doped hydroxyapatite (Cu/Zn HA) was synthesized by chemical precipitation. Cu/Zn HA, epigallocatechin gallate (EGCG), and Cu/Zn HA+EGCG were separately added to photoinitiators, and methacrylated gelatin (GelMA) was added to the photoinitiator solutions. After UV irradiation at 405 nm for 20 s, four hydrogels were prepared: GelMA (G), Cu/Zn HA/GelMA (G-Cu/Zn HA), EGCG-modified GelMA (G-E), and EGCG-modified Cu/Zn HA/GelMA (G-E-Cu/Zn HA). The microstructure, compressive mechanical properties, swelling, degradation, and release kinetics of metal ions and EGCG were characterized. Antibacterial properties were evaluated against Staphylococcus aureus and Escherichia coli using agar plate coating, live/dead staining, and scanning electron microscopy. Cytocompatibility was assessed with MC3T3-E1 cells via live/dead staining and CCK-8 assay. Osteogenic activity was evaluated after osteogenic induction using alkaline phosphatase staining, alizarin red S staining, and osteogenic-related gene expression. RESULTS AND CONCLUSION: Scanning electron microscopy showed porous internal structures in all hydrogels, with G and G-E having relatively smooth surfaces, while G-Cu/Zn HA and G-E-Cu/Zn HA had increased surface roughness. Compressive stresses were 10.48, 12.91, 23.64, and 41.03 kPa for G, G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA, respectively. Compared with G, the swelling time and equilibrium swelling ratio decreased in G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA. G-E-Cu/Zn HA exhibited prolonged degradation. G-Cu/Zn HA and G-E-Cu/Zn HA released Cu2+, Zn2+, and Ca2+ over 30 days, with G-Cu/Zn HA releasing more Cu2+ and Zn2+ than G-E-Cu/Zn HA. G-E-Cu/Zn HA significantly inhibited the burst release of EGCG compared with G-E. Antibacterial assays showed that all modified hydrogels inhibited bacteria, with G-E-Cu/Zn HA showing the strongest effect. All hydrogels were cytocompatible. Osteogenic assays showed that G had the weakest osteogenic ability, while G-E-Cu/Zn HA had the strongest. CONCLUSION: The EGCG-modified Cu/Zn HA/GelMA composite hydrogel exhibits excellent antibacterial and osteogenic properties.
1. Introduction
In recent years, bone defects caused by trauma, infection, tumors, and congenital diseases have led to a rapid increase in the demand for bone repair materials [1]. Clinically, autologous bone grafting is the gold standard for bone defect treatment, but its application is limited by insufficient sources and donor site morbidity; allogeneic bone grafting faces risks of immune rejection and disease transmission [2]. Moreover, infection during bone defect repair is a major clinical challenge. Bacterial invasion at the defect site activates the immune system, leading to excessive inflammation and a series of severe consequences [3-4]. In the inflammatory microenvironment, the function and activity of osteoblasts are inhibited, impeding new bone formation [5]. Chronic bacterial infection can progressively destroy bone tissue, potentially leading to osteomyelitis; if not controlled, bacteria may spread through the bloodstream, causing systemic infections such as sepsis, directly threatening patient life [6]. Traditional repair methods often fail to simultaneously achieve infection control and tissue regeneration [7]. Therefore, developing hydrogel scaffolds with excellent biocompatibility, antibacterial function, and effective bone regeneration guidance has become a research hotspot.
Methacrylated gelatin (GelMA), a photocrosslinkable polymer derived from natural gelatin, has good cytocompatibility, degradability, and injectability, and has gained widespread attention in bone tissue repair [8]. However, GelMA hydrogels have relatively low mechanical strength, insufficient to provide adequate support during bone repair [9]; they also lack key components that induce osteogenesis, limiting their standalone use.
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ZHOU Yunqi, LIU Xu, XIAO Dongqin, LI Xingping, SHI Feng, ZHANG Bo, PU Chao, LUO Xuwei, ZHANG Chengdong (2026). Fabrication and characterization of hydrogels with both antibacterial and osteogenic functions. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21451
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Frequently Asked Questions
What is the main objective of this study?
The main objective was to prepare a hydrogel with both antibacterial and osteogenic functions for bone tissue repair, by incorporating copper/zinc-doped hydroxyapatite and epigallocatechin gallate into methacrylated gelatin.
How was the composite hydrogel fabricated?
Copper and zinc co-doped hydroxyapatite (Cu/Zn HA) was synthesized by chemical precipitation. Cu/Zn HA, EGCG, or both were added to photoinitiators, and GelMA was mixed with these solutions. The mixtures were cured under 405 nm UV light for 20 seconds to form four hydrogels: G, G-Cu/Zn HA, G-E, and G-E-Cu/Zn HA.
What were the key findings regarding antibacterial activity?
The G-E-Cu/Zn HA hydrogel exhibited the strongest antibacterial activity against Staphylococcus aureus and Escherichia coli, attributed to the synergistic effects of Cu2+/Zn2+ ions and EGCG.
Did the hydrogels support cell viability and osteogenic differentiation?
All hydrogels showed good cytocompatibility with MC3T3-E1 cells. The G-E-Cu/Zn HA hydrogel significantly enhanced osteogenic differentiation, as indicated by increased alkaline phosphatase activity, mineralization, and osteogenic gene expression.
What is the significance of the release kinetics?
The G-E-Cu/Zn HA hydrogel controlled the release of Cu2+, Zn2+, and EGCG, reducing burst release and providing sustained therapeutic effects, which is beneficial for long-term bone repair.
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