Brief introduction of research

Promoting the repair of bone infection through biomaterials is a major challenge for researchers and clinicians. Using the natural reversible recognition strategy of glycopeptide antibiotic Vancomycin (Van) and its targeted dipeptide D-Ala-D-Ala (AA), we designed and developed a dynamic network hydrogel system containing osteogenic growth peptide (OGP) to simulate peripheral hematoma for the repair of infectious fractures. The results showed that the hydrogel system could effectively sterilize and promote bone differentiation. Further studies showed that the hydrogel system could reshape the local inflammatory microenvironment, simultaneously inhibit infection, promote bone formation, and achieve natural and functional bone healing. (Figure 1)

The researchers prepared Van monomer and AA monomer by NHS-ester crosslinking reaction, and then synthesized Van AA-OGP hydrogel system by phototriggered polymerization. The injectable and self-healing properties of the hydrogel were verified by morphological experiments (Fig. 2D, E, I). Rheology showed that the viscoelasticity of Van-AA-OGP hydrogel was similar to that of hematoma (Fig. 2J-K). In addition, the Van-AA-OGP hydrogel system also showed significant bactericidal effect (Fig. 2N) and retained good biological activity (Fig. 2P).

In vitro studies showed that the Van-AA-OGP hydrogel system promoted the expression of a series of osteogenic genes and proteins (Fig. 3B-G, J), and the expression of alkaline phosphatase and the formation of calcium nodules 7 and 14 days after induction of differentiation, respectively (Fig. 3A, H, I), promoting the process of osteogenic differentiation.

In order to explore the antibacterial effect of Van-AA-OGP hydrogel system in vivo, the researchers' experiments confirmed that Van-AA-OGP hydrogel system maintained good antibacterial properties in vivo and effectively eliminated tissue pathogenic bacteria (FIG. 4).

The Van-AA-OGP hydrogel system reversed the inflammatory microenvironment during infection and reshaped the normal local microenvironment in vivo, thus effectively restoring the physiologic bone healing process (Figure 5).

In the mouse infectious fracture model, the Van-AA-OGP hydrogel system effectively promoted bone formation, promoted the physiological healing of long bone fractures, accelerated the bone maturation process of endochondral osteogenesis, reshaped the complete structure of long bone and improved bone strength (FIG. 6, 7).

In summary, this study used molecular recognition strategies to develop a dynamic hydrogel network that mimics hematoma, which can remove local pathogenic bacteria, restore inflammatory microenvironment, and promote fracture healing. It provides a new idea for infective fracture bactericidal biomaterials.