0D Amplification Strategies Reshape Bone Interface Niches via Biointernalization Effects

Abstract 0D biomaterials (0DBMs) can serve as carriers to enhance and extend the regulatory effects of biological cues they transport on cell fate via bacterial/mammalian cell internalization. However, accurately delivering and amplifying biosignals through 0DBMs remains challenging to cope with ecological niche destabilization induced by factors such as trauma or infection. Herein, the “zero‐dimensional amplification” approach is employed to develop a surface carboxylate carbon dot (CQD‐COOH) conjugated with a neutrophil constitutive peptide (LL‐37), resulting in the formation of a 0D peptide quantum dot (LQD). Hydrogel‐released LQDs, when internalized by bacteria, cause the bacteria to programmatically rupture and die, whereas LQDs internalized by mesenchymal stem cells (MSCs) activate the cellular CXCL12/CXCR4 signaling axis, which directs the stem cells to homing and anchor to the surface of the hydrogel coating. Notably, this strategy of “zero‐dimensional amplification” enables the antimicrobial performance of LL‐37 to be boosted approximately 1.3‐fold, significantly extending the transmission efficiency of biosignals. Meanwhile, 0D lipid nanoparticles (lipo‐NPs) with targeting function incorporated into the hydrogel could deliver the bio‐small molecule MK‐4 to MCSs and induce their endocytosis, further enhancing osseointegration. Thus, the hydrogel coating (HGLL) under this strategy can significantly remodel the ecological niche of the implant–bone interface in infected environment.