Stem Cell Fishing at Bone-Implant Interface: A Cell-Clicking Bioadhesion Strategy to Enhance Osteointegration

Insufficient mesenchymal stem cells (MSCs) at bone-implant interfaces hinder osseointegration and implant success. Although stem cell therapies are promising, in situ recruitment and high-efficiency localization of target cells remain challenging. This study proposes a “cell-clicking” strategy for in situ “fishing” bone marrow MSCs (BMSCs) at the bone-implant interface. The bidirectional binding, based on a clickable biomimetic peptide with mussel-like adhesive and bioorthogonal molecular binding abilities, enables rapid, precise, and stable chemical tethering of azide-modified BMSCs (BMSCs-Az) at the initial phase after implantation. Thereafter, a steady transition of the tethered stem cells into chemo-biological co-adhesion states improves interfacial osteogenesis. This study first verifies that BMSCs-Az can be captured and stably bound to the surface of clickable biomimetic peptide-modified implants both in vitro and in vivo. Additionally, the immunomodulatory activity of BMSCs-Az can alter macrophage polarization. The synergistic effect of BMSCs-Az immunomodulation and in situ cell fishing-mediated recruitment enhances osteogenic efficiency and reinforces biomechanical integration at the bone-implant interface. In conclusion, this study provides a new inspiration for osteo-implants in stem cell-based regenerative medicine to develop rapid, precise, and stable stem cell recruitment strategies for high-efficiency tissue regeneration.