Zn-based biodegradable metals (BMs) are regarded as revolutionary biomaterials for bone implants. However, their clinical application is limited by insufficient mechanical properties, delayed in vivo degradation, and overdose-induced Zn²⁺ toxicity. Herein, innovative multi-material additive manufacturing (MMAM) is deployed to construct a Zn/titanium (Ti) hetero-structured composite. The biodegradation and biofunction of Zn exhibited intriguing characteristics in composites. A potential difference of about 300 mV naturally existed between Zn and Ti. This natural potential difference triggered galvanic coupling corrosion, resulting in 2.7 times accelerated degradation of Zn. The excess release of Zn²⁺ induced by accelerated degradation enhanced the antibacterial function. A voltage signal generated by the natural potential difference also promoted in vitro osteogenic differentiation through activating the PI3K-Akt signaling pathway, and inhibited the toxicity of overdose Zn²⁺in vivo, significantly improving bone regeneration. Furthermore, MMAM technology allows for the specific region deployment of components. In the future, Ti and Zn could be respectively deployed in the primary and non-load-bearing regions of bone implants by structural designs, thereby achieving a functionally graded application to overcome the insufficient mechanical properties of Zn-based BMs. This work clarifies the functional optimization mechanism for multimetal bone implants, which possibly breaks the application dilemma of Zn-based BMs.

Background: Delayed healing of maxillofacial soft tissue wounds is closely associated with inffammatory injury and mitochondrial dysfunction in fibroblasts, while effective therapeutic strategies remain limited. This study investigated whether activation of the mechanosensitive ion channel Piezo1 by Yoda1 could promote wound healing. Methods: An LPS-induced inflammatory model was established in human gingival fibroblasts (HGFs) and treated with Yoda1. Intracellular calcium influx, cell viability, oxidative stress, mitochondrial membrane potential, apoptosis, migration, wound closure, and type I collagen expression were assessed. The involvement of the PINK1/Parkin-mediated mitophagy pathway was analyzed. An in vivo inflammatory wound model was used to evaluate therapeutic efficacy. Results: Yoda1 significantly increased intracellular calcium influx, improved cell viability, reduced oxidative stress, restored mitochondrial membrane potential, and inhibited apoptosis in LPS-treated HGFs. It also enhanced HGFs migration, wound closure, and type I collagen expression in vitro . Mechanistically, these effects were associated with activation of the PINK1/Parkin-mediated mitophagy pathway. In vivo , Yoda1 accelerated wound closure, accompanied by increased collagen deposition and improved tissue regeneration. Conclusion: Activation of Piezo1 by Yoda1 can alleviate its inflammatory damage by restoring mitochondrial homeostasis and regulating the cellular functions of HGFs. Piezo1 may be a promising therapeutic target for promoting maxillofacial wound repair.