Prolonged or excessive inflammation may lead to impaired vascularization and bone regeneration, hindering the normal repair process of bone tissue. Although the regulation of inflammation is crucial for promoting a conducive microenvironment for bone regeneration, individual anti-inflammatory interventions frequently are inadequate in facilitating effective bone repair. Here, a multifunctional hydrogel (GelMA-ZC-Yoda1) with multifaceted therapeutic strategy was designed by integrating Zinc/Cerium-layered double oxide nanozyme (ZnCe-LDO, with catalase-like activity) and Yoda1 (an activator of the mechanically sensitive Piezo1 ion channel) into photocurable GelMA hydrogel. The ZnCe-LDO nanozyme in the hydrogel promoted M2 macrophage polarization by reprogramming inflammatory macrophages, establishing a favorable microenvironment, while the sustained release of zinc and cerium ions facilitated osteo/angiogenesis. Additionally, the Yoda1 released from the hydrogel chemically simulated a mechanical signal to activate the Piezo1 channel, regulating osteo/angiogenesis via the Piezo1/YAP1 signaling pathway. In vivo findings indicated that the GelMA-ZC-Yoda1 hydrogel application improved the inflammatory microenvironment and effectively enhanced osteo/angiogenesis in a rat calvaria defect model. This study supports the advancement of injectable hydrogels with multifunction, including inflammatory macrophage reprogramming and promotion of osteo/angiogenesis.
Xiao et al. (Fri,) studied this question.