Multifunctional Hydrogels for Bone Defect Repair: From Microenvironment Remodeling to Structural–Functional Integration

BackgroundCritical-sized bone defects resulting from trauma, tumor resection, infection, and congenital deformities represent a major clinical challenge worldwide. While autografts remain the gold standard for bone repair, their limitations—including donor site morbidity, insufficient supply, and inability to conform to irregular defect geometries—have driven the search for alternative biomaterial-based strategies.Hydrogels, as three-dimensional hydrophilic polymeric networks, have emerged as a highly promising class of biomaterials for bone tissue engineering. Their tunable physicochemical properties, excellent biocompatibility, and ability to mimic the native extracellular matrix (ECM) provide a conducive microenvironment for cell adhesion, proliferation, and osteogenic differentiation. However, conventional hydrogels often suffer from static properties that cannot dynamically adapt to the complex, multistage process of bone healing—which encompasses inflammation, angiogenesis, osteogenesis, and remodeling. A deeper understanding of how hydrogel composition, crosslinking architecture, and surface chemistry govern these biological responses (i.e., structure–property–function relationships) is therefore essential to guide rational material design.Recent advances have highlighted the urgent need for multifunctional hydrogel systems that can actively participate in and coordinate the bone regeneration cascade. Key unresolved challenges include:• Programmed, spatiotemporally controlled release: how to engineer hydrogels that sequentially deliver bioactive cues (growth factors, ions, therapeutic agents) to guide each stage of the healing process.• Stimulus-responsive 'smart' design: how to develop hydrogels that sense and adapt to the dynamic pathological microenvironment of bone defects (e.g., reactive oxygen species, pH shifts, enzymatic activity, mechanical forces).• Structural–functional integration: how to unify structural features (injectability, self-healing, controlled porosity, tunable mechanics) with biological functionalities (anti-inflammation, immunomodulation, pro-angiogenesis, osteoinduction) within a single biomaterial platform.• Translational validation: how to establish reliable in vitro and preclinical in vivo models that rigorously evaluate structure–property–function relationships before clinical translation.GoalThis Research Topic aims to consolidate cutting-edge original research and comprehensive review articles addressing the design, characterization, and translational application of multifunctional hydrogels for bone defect repair. By bridging materials science, mechanobiology, immunology, and clinical translation, this Topic seeks to:• Advance fundamental understanding of the structure–property–function relationships that govern hydrogel performance in the complex bone regeneration microenvironment.• Highlight emerging design strategies for smart, stimuli-responsive, and structurally integrated hydrogel platforms capable of orchestrating the multistage bone healing cascade.• Promote rigorous preclinical validation by encouraging contributions that employ well-characterized in vitro, ex vivo, and in vivo models to demonstrate biological efficacy, biocompatibility, and osseointegration.• Accelerate clinical translation by identifying critical knowledge gaps and fostering interdisciplinary collaboration between biomaterial scientists, biomedical engineers, and clinicians.Scope and Information for AuthorsWe particularly welcome contributions that provide detailed, mechanistically grounded insights into the structure–property–functional relationships of hydrogel biomaterials in biological systems, whether studied in vitro, ex vivo, or in vivo. Submissions focused on, but not limited to, the following themes are encouraged:1. Microenvironment-responsive 'smart' hydrogels (pH-, ROS-, enzyme-, thermal-, light-, or magnetic field-responsive) for on-demand therapeutic delivery and dynamic bone regeneration.2. Multifunctional hydrogel systems integrating anti-inflammatory, immunomodulatory, pro-angiogenic, and osteogenic properties for synergistic bone repair.3. Injectable and self-healing hydrogels for minimally invasive treatment of complex and irregular bone defects.4. Hydrogel scaffolds with precisely controlled architectures and tunable mechanical properties: design principles, material formulation, and characterization of printability and shape fidelity.5. Hydrogel-based delivery platforms for encapsulation and controlled release of biologics (growth factors, exosomes, therapeutic agents): material design, loading efficiency, release kinetics, and bioactivity retention.6. Hydrogel-mediated spatiotemporal regulation of bone remodeling coupling (osteogenesis–angiogenesis coupling, macrophage polarization, etc.).7. Mechanobiological and computational approaches to understand and optimize the mechanical performance and degradation behavior of hydrogel biomaterials in bone repair.8. Preclinical in vivo evaluation of hydrogel-based bone repair biomaterials, including biocompatibility, immunological response, degradation, and osseointegration assessment in small and large animal models.Article typesThis Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:• Brief Research Report• Case Report• Data Report• Editorial• FAIR² Data• FAIR² DATA Direct Submission• General Commentary• Hypothesis and Theory• Methods• Mini Review• Opinion• Original Research• Perspective• Review• Systematic Review• Technology and CodeArticles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders. Topic editors: Nanning Lv, MARCO ANTONIO ALVAREZ-PEREZ, Jiaying Li, Mingming Liu Source: https://www.frontiersin.org/research-topics/81331/multifunctional-hydrogels-for-bone-defect-repair-from-microenvironment-remodeling-to-structural-functional-integration