Functionalized layered double hydroxide coatings on biodegradable Zn-Mg alloy enhance osteogenesis via the Wnt/β-catenin and PI3K/Akt signaling pathways.

Abstract

Biodegradable zinc (Zn)-based implants have shown great potential for orthopedic applications. However, excessive Zn²⁺ release during the degradation of Zn-based implants results in compromised biocompatibility and suboptimal osteogenic activity. Layered double hydroxides (LDHs), known for the capability to regulate degradation behavior while also exhibiting remarkable biocompatibility and osteoinductive capacity, offer a promising solution. Herein, Zn-Al LDH coating was fabricated on Zn-0.8Mg alloy substrates via an in-situ growth method. Subsequently, the effect of solution pH on the degradation behavior, cytotoxicity and osteogenic capacity of the LDH coating was investigated. Benefiting from the distinctive characteristics of the constructed LDH coating, the Zn-0.8Mg alloy with LDH coating prepared at pH=11 exhibited uniformly distributed nanosheets and demonstrated favorable corrosion resistance. During degradation, the low concentration of Zn²⁺ released from LDH-modified Zn-0.8Mg alloy implants fabricated at pH=11 improved cytocompatibility, facilitated osteoblasts proliferation and osteogenic differentiation in vitro, and accelerated bone regeneration in vivo. Furthermore, the formation mechanism of the LDH coating on Zn-based alloy was elucidated. Transcriptomic analysis further revealed that the LDH coating promoted osteogenic differentiation by activating the Wnt/β-catenin and PI3K/Akt signaling pathways. Collectively, this work offered a feasible strategy to enhance the biocompatibility and bone regeneration capability of Zn-based alloys, broadening their biomedical application. STATEMENT OF SIGNIFICANCE: As highly promising biodegradable metals, Zn-based alloys have become a research hotspot in the fields of dentistry and orthopedics. However, the excessive Zn²⁺ release during initial degradation may cause adverse biological responses, limiting their clinical translation. In this study, we fabricated LDH-coated Zn-0.8Mg alloy by in-situ growth method at different pH values to regulate degradation behavior, improve biocompatibility and enhance osteogenic properties. This study demonstrated that LDH-coated Zn-0.8Mg alloy fabricated at pH=11 exhibited significantly optimized corrosion resistance, biocompatibility and osteogenic properties, thereby expanding its potential for implant applications.