Overcoming the challenges of bone defects! Biomimetic Matrix Hydrogel Creates Bone Organoids for Efficient Skull Regeneration, as Reported in Bioactive Materials

Source: BioValley Original

A study has developed a biomimetic matrix hydrogel incorporating multiple functional components and a dual-network structure. This hydrogel enables the sequential construction of vascularized and mineralized bone organoids, supporting dynamic culture in vitro and ectopic osteogenesis in vivo. It effectively repairs cranial bone defects, offering a novel strategy for bone tissue regeneration.

In daily life, fractures and bone injuries occur frequently, significantly impacting quality of life. For large bone defects, traditional treatments such as autografts and allografts face limitations like donor shortage and immune rejection, posing major challenges to bone repair. In this context, bone organoids—which closely mimic the physiological properties of natural bone—have gained attention as a promising approach in bone regeneration research.

A recent study published in Bioactive Materials, titled "Sequential construction of vascularized and mineralized bone organoids using engineered ECM-DNA-CPO-based bionic matrix for efficient bone regeneration," presents a breakthrough in this field.

The study focuses on developing a novel engineered biomimetic matrix hydrogel to construct vascularized and mineralized bone organoids for efficient bone regeneration. By incorporating calcium phosphate oligomers (CPO) into a combination of bone-derived decellularized extracellular matrix (ECM) and salmon-derived DNA, and utilizing photo-crosslinking and dynamic self-assembly strategies, the researchers successfully fabricated a biomimetic matrix hydrogel with multifunctional components and a dual-network structure.

Figure 1. Schematic diagram of the sequential construction of vascularized and mineralized bone organoids using the engineered ECM-DNA-CPO biomimetic matrix hydrogel

The hydrogel preparation and characterization demonstrated a rigorous process: dECM was validated via histological staining to confirm cell removal and collagen retention; CPO appeared as nanoparticles comprising mixed calcium-phosphate compounds, providing a mineralization foundation; salmon DNA self-assembled into a hydrogel, with its negative charge promoting mineralization nucleation. The resulting mECM-DNA-CPO hydrogel exhibited a uniform porous structure, favorable hydrophilicity, mechanical properties, viscoelasticity, and a suitable degradation rate, creating an optimal environment for subsequent cell culture and differentiation.

Figure 2. Preparation process and performance characterization of the biomimetic matrix hydrogel

In cellular experiments, the hydrogel showed outstanding performance: it significantly enhanced the migration and proliferation of bone marrow mesenchymal stem cells (BMSCs), with cells distributing evenly and maintaining high viability. The hydrogel also accelerated osteogenic differentiation of BMSCs, increasing early alkaline phosphatase staining intensity and late calcium deposition, while upregulating osteogenesis-related genes and proteins. For human umbilical vein endothelial cells (HUVECs), the hydrogel promoted migration, proliferation, and angiogenesis, forming clear vascular network structures and upregulating related gene expression. Transcriptomic analysis further revealed that the hydrogel enhances osteogenic differentiation and angiogenesis through multiple mechanisms.

Figure 3. Construction of mineralized bone organoids via dynamic culture in vitro

In experiments constructing bone organoids in vitro, dynamic culture systems were more conducive to bone organoid formation than static cultures, with significantly increased mineralization over time. In vivo experiments showed that the hydrogel degraded effectively and formed vascularized bone organoids when implanted subcutaneously in nude mice, with the mECM-DNA-CPO group exhibiting the most pronounced mineralization and vascularization. In a mouse cranial defect model, the mECM-DNA-CPO hydrogel significantly promoted in situ vascularized bone repair, reducing defect area, enhancing new bone formation, improving bone regeneration capacity, and demonstrating good biocompatibility.

Figure 4. Engineered biomimetic matrix hydrogel promotes in situ bone repair in a cranial defect model

This study successfully developed an engineered biomimetic matrix hydrogel that demonstrates outstanding performance in constructing mineralized and vascularized bone organoids, providing an innovative strategy for bone tissue repair. In the future, with continued in-depth research, this approach is expected to offer new solutions for clinical treatment of bone defects, benefiting more patients. It is believed that through the persistent efforts of researchers, the field of bone tissue repair will achieve further breakthroughs, contributing to the advancement of human health.

Reference:

Gai T, Zhang H, Hu Y, et al. Sequential construction of vascularized and mineralized bone organoids using engineered ECM-DNA-CPO-based bionic matrix for efficient bone regeneration. Bioact Mater. 2025;49:362-377. Published 2025 Mar 14. doi:10.1016/j.bioactmat.2025.02.033

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