Biomimetic Periodontal Ligament Transplantation Activated by Gold Nanoparticles Protects Alveolar Bone

Stem cell therapy might be a promising method to stimulate alveolar bone regeneration, which is currently a major clinical challenge. However, its therapeutic features largely depend on pretreatment and transplantation preparation. Herein, a novel biomimetic periodontal ligament transplantation composed of human periodontal ligament stem cells (hPDLSCs) pretreated with gold nanocomplexes (AuNCs) and embedded in a type‐I collagen hydrogel scaffold is developed to protect alveolar bone from resorption. AuNCs are readily absorbed by primary hPDLSCs, with limited cytotoxicity, and promote osteogenic differentiation of hPDLSCs effectively in vitro. In addition, the AuNCs‐induced hPDLSCs are encapsulated with type‐I collagen hydrogel scaffold to mimic their native physiological niche, and then are transplanted into a rat model of alveolar bone resorption. Both micro‐computed tomography (micro‐CT) and immunohistochemical assays demonstrate that alveolar bone loss is significantly prevented. Furthermore, the underlying therapeutic mechanism is elucidated, in which transplantation‐activated osteogenesis is associated with autophagy, which enables bone remodeling and regeneration. This study provides critical insight into the role of PDLSCs in bone homeostasis and proposes an innovative AuNCs‐based strategy for stem cell therapy in bone regeneration. Gold nanoparticles (AuNPs) are synthesized as AuNP‐poly‐l‐lysine hydrobromide‐rhodamine B isothiocyanate nanocomplexes and are used as a pretreatment for human periodontal ligament stem cells (hPDLSCs) in vitro. The biomimetic periodontal ligament transplantation is fabricated by the pretreated hPDLSCs embedded in type‐I collagen hydrogel scaffold and applied in an animal model of alveolar bone loss. The transplantation significantly promotes bone regeneration and protects bone morphometry.