Lithium fine-tunes biodegradation of Zn-based implant to promote osseointegration through immunomodulation

The intricate degradation dynamics exhibited by biodegradable alloys significantly influence host responses during the implantation process, posing challenges in achieving stable osseointegration. It is thus critical to tailor the biodegradation profiles of these implants to establish a conductive tissue microenvironment for bone tissue regeneration. In this study, we demonstrate that Zn-Li alloy forms a layer of Li-containing degradation products at the bone-implant interface to accommodate the bone regeneration process. During the early inflammatory phase, the controlled release of lithium ions (Li + ) and zinc ions (Zn 2+ ) from the alloy induces chemokine (C-C motif) ligand 5 (CCL5) production from macrophages, which promotes the recruitment and differentiation of osteoblastic lineage cells. As a protective bone-implant interface is formed subsequently, the active Zn 2+ release from Zn-Li alloy is suppressed while Li + continues to exhibit anti-inflammatory effects and inhibit osteoclastogenesis. Therefore, the presence of Li in Zn-based alloy prevents the prolonged inflammation and fibrous capsulation typically seen in pure Zn implants. Our findings offer valuable insights into the development of novel biodegradable implants aimed at achieving osseointegration through bioadaption. The intricate degradation dynamics exhibited by biodegradable alloys significantly influence host responses during the implantation process. Lithium alloying tailored the biodegradation profile of Zn-based implant to achieve bioadaption to the bone. With Li-containing protective layer formed at the bone-implant interface, biodegradation of Zn-Li implant creates a favorable immune microenvironment to promote osseointegration. • Zn-Li alloy forms a Li-containing degradation layer at the bone-implant interface to adapt the bone regeneration process. • Zn-Li alloy induces the secretion of CCL5 to promote the recruitment and differentiation of osteoblastic lineage cells. • Li in Zn-based alloy prevents the prolonged inflammation and fibrous capsulation typically seen in pure Zn implants.