Hydrogel-Based Bone Organoid Engineering: Microenvironmental and Mechanical Control of Maturation, Vascularization, and Function

Bone is a highly organized, vascularized, mineralized, and mechanically responsive tissue whose development, remodeling, and repair depend on coordinated interactions among osteogenic cells, endothelial cells, stromal cells, marrow-associated cells, and osteoclast-lineage cells. Bone organoids provide emerging platforms to recapitulate these multicellular and matrix-dependent processes in vitro, offering new opportunities for modeling skeletal development, bone diseases, craniofacial regeneration, and biomaterial-guided repair. However, current bone organoid systems often lack defined and tunable extracellular microenvironments, which limits reproducibility, vascular integration, mineralized matrix maturation, and mechanistic interpretation. Hydrogels are particularly suitable for engineering bone organoid niches because their biochemical composition, stiffness, viscoelasticity, porosity, degradability, ligand presentation, mineral-associated cues, and transport properties can be systematically controlled. This Research Topic focuses on hydrogel-based microenvironmental and mechanical strategies for guiding bone organoid self-organization, vascularization, mineralization, remodeling, and functional maturation.

This Research Topic aims to advance hydrogel-based bone organoid engineering from empirical 3D culture toward rationally designed, quantitatively defined, and mechanistically informed tissue models. We seek studies that investigate how hydrogel microenvironmental parameters regulate bone organoid formation and function, including osteogenic lineage specification, endothelial organization, vascular network formation, mineralized matrix deposition, osteoclast-related remodeling, cell-cell mechanical coupling, mechanotransduction, and mechanical memory. Particular emphasis will be placed on work that establishes causal or quantitative relationships between hydrogel properties and organoid phenotypes, rather than purely descriptive culture outcomes. Relevant approaches may include engineered natural, synthetic, hybrid, mineralized, dynamic, or stimuli-responsive hydrogels, combined with advanced imaging, biosensing, single-cell or spatial profiling, computational modeling, or functional assays. By integrating hydrogel design with bone-specific biological readouts, this collection aims to define design principles for constructing reproducible and functionally mature bone organoid systems for skeletal biology, disease modeling, craniofacial research, and regenerative engineering.

We welcome articles in the following areas, including but not limited to:
• Defined synthetic, natural, hybrid, and mineralized hydrogels for bone organoid culture;
• Hydrogel mechanical, viscoelastic, biochemical, architectural, degradation-related, mineral-associated, and transport regulation of bone organoid maturation;
• Hydrogel strategies for vascularized, multicellular, osteogenic, osteoclastic, marrow-like, dental, or craniofacial bone organoid systems;
• Dynamic, degradable, stimuli-responsive, or mechanically active hydrogel microenvironments;
• Mechanotransduction, cell-cell mechanical coupling, mechanical memory, and gene regulatory network remodeling in bone organoids;
• Quantitative imaging, single-cell and spatial profiling, biosensing, or computational modeling approaches that directly reveal hydrogel-bone organoid interactions.

Disease modeling, drug testing, organ-on-chip, microfluidic, 3D printing, craniofacial tissue modeling, and regenerative medicine studies are within scope only when the hydrogel microenvironment is a central experimental variable. Submissions should include a clearly defined hydrogel or engineered microenvironment component and demonstrate its direct influence on bone organoid self-organization, maturation, vascularization, mineralization, remodeling, or tissue-relevant function.