Bioinspired 3D-Hydrogels for Bone-Tissue Regeneration

Bone is a highly regenerative tissue, thus in young individuals, most fractures are spontaneously healed. Yet, in cases of large bone defects, as observed after bone tumor resections, severe fractures, or inflammatory diseases, the template for orchestrated regeneration is lacking. Therefore, reconstruction of bone defects continues to be an enormous clinical challenge. Although autogenic, allogeneic, and xenogeneic bone materials have been widely applied to treat such defects, they possess potential limitations, including limited availability and donor site morbidity, potential immunogenicity, and risk for disease transmission. Biomimetic materials that can stimulate and accelerate bone formation represent a promising alternative. The implementation of such matrices for bone regeneration is hampered by several requirements, including a 3D porous architecture, biological activity, biocompatibility, and immunomodulation.<br/>Here, we applied a co-assembly approach using hydrogel-forming peptides, resulting in a synergistic modulation of their mechanical properties to form extraordinarily rigid hydrogels which supported osteogenic differentiation based on cells-mechanosensing. Furthermore, we designed a multi-component scaffold composed of polysaccharides, short self-assembling peptides, and bone minerals. We demonstrate the formation of a rigid, yet injectable, and 3D printable hydrogel without the addition of cross-linking agents. The formed composite hydrogel displays a nanofibrous structure, which mimics the extracellular matrix and exhibits thixotropic behavior and a high storage modulus. This composite scaffold induces osteogenic differentiation and facilitates calcium mineralization.<br/>This work provides a conceptual framework for the utilization of co-assembly strategies to push the limits of nanostructure physical properties obtained through self-assembly for the design of new biomaterials for tissue engineering applications.