Conventional gelatin (Gel) and alginate hydrogels possess excellent biocompatibility. Their high water content and three-dimensional porous structure mimic the extracellular matrix, facilitating nutrient transport and metabolic waste removal. However, their application in bone tissue engineering is hindered by insufficient mechanical strength, rapid degradation, and weak osteogenic activity. In this study, we developed a self-cross-linking hydrogel (GOP hydrogel) reinforced with calcium phosphate oligomers (CPO). The network was formed via a Schiff base reaction between periodate-oxidized sodium alginate (OSA) and gelatin, with small-sized CPO acting as an inorganic cross-linker to enhance intermolecular bonding and strengthen the polymeric network. The composite hydrogel was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), and its mechanical properties, degradation behavior, and swelling capacity were evaluated. The GOP hydrogel exhibited excellent biocompatibility, supported cell viability and osteogenic differentiation, and promoted vascularized healing in critical-sized calvarial defects in rats. With the incorporation of CPO, the hydrogels exhibited enhanced mechanical strength, regulated degradation and swelling, and improved mineralization and osteogenic activity. These findings indicate that the GOP hydrogel meets the key requirements for bone tissue engineering scaffolds and holds considerable promise for bone regeneration applications.
Lingfei Liu, Ke Li, Ziyi Yan et al.· ACS Applied Bio Materials· 0 citations
Critical-sized bone defects (CSDs) represent a major clinical challenge due to their limited self-healing capacity. Conventional hydrogels incorporating crystalline hydroxyapatite (HA) often fail to recapitulate the hierarchical nanostructure of native bone, leading to suboptimal regeneration outcomes. To overcome this, we developed a biomimetic hydrogel by molecularly integrating amorphous calcium phosphate oligomers (CPO) into gelatin methacryloyl (GelMA), enabling a bone-like organic-inorganic hybrid network. This composite exhibits outstanding performance: an ultimate strength of 192 kPa at 18 wt% CPO confirms robust mechanical reinforcement, while 54% mass retention after 56 days underscores exceptional degradation resistance and dose-dependent bioactivity, evidenced by a two-fold upregulation of alkaline phosphatase (ALP) activity. The amorphous CPO facilitates biomimetic HA nucleation within the GelMA matrix, mimicking the natural mineralization process. In a rat calvarial CSD model, the hydrogel promoted 60% bone volume regeneration within 12 weeks, significantly outperforming conventional composites, through seamless host integration, vascularized trabecular bone formation, and a collagen-mineral hierarchy resembling native osteogenesis. This study establishes CPO as a transformative component that converts passive scaffolds into bioactive osteogenic microenvironments, offering a clinically viable strategy for complex bone regeneration.
Yue Shu, Meizi Zhang, Bo Li et al.· Journal of Biomedical Materi...· 0 citations