Chronic infected wounds experience delayed healing due to persistent bacterial colonization, excessive accumulation of reactive oxygen species (ROS), and prolonged inflammation. Although adhesive hydrogels are promising as wound dressings, challenges in achieving strong tissue adhesion coupled with adequate internal cohesion have hindered their clinical application. Here, we developed a multifunctional adhesive hydrogel designed around a cohesion–adhesion balance strategy for infected wound treatment. Specifically, we synthesized a gelatin microsphere-reinforced adhesive hydrogel (Gel-GM) by embedding gelatin microspheres (GMs) and the antimicrobial peptide LL-37 into a dopamine-grafted alginate network. Incorporation of GMs strengthened the hydrogel network through increased intermolecular interactions, enhancing cohesive strength while preserving sufficient exposed catechol groups to ensure interfacial adhesion. In vitro studies demonstrated that Gel-GM significantly improves ROS scavenging, promotes anti-inflammatory M2 macrophage polarization, and enhances fibroblast proliferation and migration. Additionally, LL-37 confers potent antibacterial activity by disrupting bacterial membranes via electrostatic interactions. In vivo evaluations revealed that Gel-GM possesses robust antibacterial and anti-inflammatory properties, effectively accelerating infected wound healing. Collectively, this study emphasizes the potential of employing a cohesion–adhesion balance approach to engineer multifunctional adhesive hydrogels for managing infected wounds.
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Repair of orofacial tissue remains a clinical challenge, as conventional materials often fail to meet multiple requirements such as biocompatibility, antibacterial activity, anti-inflammatory effects, and tissue regeneration. Zinc (Zn)-containing biomaterials have recently emerged as a research focus due to their unique biological properties, offering new strategies to address this challenge. This article summarizes the latest research on Zn-containing bioactive materials in this field. It first elucidates the mechanisms by which these biomaterials exert antibacterial, anti-inflammatory, and tissue-regenerative effects. The Zn2+ released during degradation inhibits bacterial growth by interfering with bacterial metabolism, remodels the immune microenvironment by regulating macrophage polarization and recruiting neutrophils, promotes fibroblast proliferation to accelerate soft tissue repair by activating signaling pathways such as PI3K/Akt, and enhances osteogenic differentiation through pathways such as Wnt/β-catenin. Based on these mechanisms, this review further elaborates on the design strategies of zinc-containing biomaterials for treating maxillofacial bone defects, fractures, periodontitis, peri-implantitis, and oral mucosal diseases, analyzing how to modulate the release behavior of Zn2+ to achieve antibacterial, anti-inflammatory and tissue-regenerative functions. Despite this progress, challenges remain, including imprecise Zn2+ release, inadequate temporal regulation, insufficient long-term biosafety data, and lack of standardized clinical translation protocols. Future research can focus on developing smart Zn2+-controlled release systems, constructing biomimetic spatiotemporal regulatory platforms, assessing long-term biosafety using advanced technologies such as organoids or organ chips, and establishing systematic clinical translation evaluation frameworks. This review aimed to provide research frameworks for further development and clinical application of Zn-containing biomaterials in orofacial reconstruction.
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Guided bone regeneration (GBR) membranes are extensively utilized in dental implantation. However, the existing GBR membranes showed insufficient space-maintaining capability and poor bone promoting ability, affecting the effectiveness of clinical bone augmentation, which in turn resulted in poor implant outcomes and even failure. In this study, we designed a novel magnesium reinforced sandwich structured composite membrane, consisting of an inner magnesium scaffold and a PLGA/collagen hybrid (mixture of poly(lactic-co-glycolic acid) and collagen) top and bottom layer. The magnesium scaffold provided mechanical support and released Mg2+ to enhance osteogenesis. The PLGA/collagen hybrid regulated membrane degradation and improved biocompatibility, promoting cell adhesion and proliferation (P < 0.05). The PLGA/collagen hybrid regulated the release of magnesium ions, such that the MgP10C (mass ratios of PLGA and collagen =100:10) group showed the best in vitro osteogenic effect. Further mechanism exploration confirmed that MgP10C membranes significantly enhanced bone defect repair via the MAPK/ERK 1/2 pathway by the Mg2+ released from the composite membranes. In rat calvarial defect and rabbit alveolar defect model (P < 0.05), the in vivo osteogenic effect of the MgP10C group was superior to that of other groups. Finite element analysis models validated the support effect of composite membranes, demonstrating lower stress and a significant reduction in strain on the bone graft in the MgP10C group. In conclusion, the magnesium-reinforced sandwich structure composite membrane, with its space-maintaining properties and osteoinductive activity, represents a new strategy for GBR and enhancing osteogenic potential that meets directly clinical needs.
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In bone tissue engineering, polycaprolactone (PCL) is a promising material with good biocompatibility, but its poor degradation rate, mechanical strength, and osteogenic properties limit its application. In this study, we developed an Mg-1Ca/polycaprolactone (Mg-1Ca/PCL) composite scaffolds to overcome these limitations. We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5, 10, and 20 wt%. Porous scaffolds with controlled macro- and microstructure were printed using the fused deposition modeling method. We explored the mechanical strength, biocompatibility, osteogenesis performance, and molecular mechanism of the Mg-1Ca/PCL composites. The 5 and 10 wt% Mg-1Ca/PCL composites were found to have good biocompatibility. Moreover, they promoted the mechanical strength, proliferation, adhesion, and osteogenic differentiation of human bone marrow stem cells (hBMSCs) of pure PCL. In vitro degradation experiments revealed that the composite material stably released Mg2+ ions for a long period; it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth. Microcomputed tomography and histological analysis showed that both 5 and 10 wt% Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects. Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect. Therefore, Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.
Statement of significance: Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects. However, there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds. This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities. Furthermore, the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold. The obtained porous scaffolds can significantly promote the regeneration of bone defects.
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