Cell membrane-coated nanomicrospheres mimicking stem cell functions enhance angiogenesis for dental pulp regeneration

Abstract

Intact and healthy dental pulp is crucial for maintaining the integrity of teeth. A variety of impairments such as infection and trauma cause irreversible pulp damage, which require removal of pulp tissue and conventional root canal filling. However, this type of treatment fails to restore vital pulp. It is still a clinical challenge to discover how to regenerate pulp and prolong the lifespan of teeth. Regenerating tissues similar to dental structures with normal functions is putatively the aim in the tooth regeneration field. Currently, researchers preliminarily achieve tooth regeneration by applying dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED). While stem cell transplantation for pulp regeneration shows promise, it faces critical challenges including complex manipulation, low cell survival rates, and storage difficulties. This study introduces a novel nanoparticle-based biomimetic system that overcomes these limitations by emulating stem cell functions. Under hypoxic conditions, SHED release concentrated pro-angiogenic factors, which were encapsulated into cell membrane-coated nanomicrospheres, creating bionic dental pulp stem cells. This innovative design enables sustained and controlled cytokine release while maintaining biocompatibility through the protective cell membrane coating. In hindlimb ischemia and pulp regeneration models, the bionic system demonstrated significantly enhanced retention (48.58% at day 7 versus minimal SHED retention), superior blood perfusion restoration (72% of normal levels), and dramatically increased vascular density (7.6-fold higher than controls). This cell-free nano-delivery platform provides a stable, immune-compatible alternative for functional tissue regeneration, addressing key limitations of conventional stem cell therapies while offering practical advantages for clinical translation in the challenging environment of narrow root canals.