Biomimetic aligned scale-like nanotopographic scaffold reprograms resorption-dominant remodeling in diabetic sockets to enhance alveolar ridge preservation.

Spatiotemporally patterned alveolar ridge resorption after tooth extraction compromises subsequent implant placement and esthetic rehabilitation. This challenge is aggravated in diabetes, where chronic inflammation and excessive osteoclast activity drive the extraction socket into an early resorption-dominant remodeling state, exacerbating ridge atrophy. Inspired by the ordered collagen-mineral hierarchy of socket bone, we engineered an aligned, scale-like nanotopographic scaffold (AT) to provide interfacial mechanical cues for regulating pathological remodeling. Transcriptomic profiling revealed broad suppression of osteoclast differentiation-associated programs and attenuation of NF-κB signaling in the AT group. AT further induced pronounced alignment-dependent cell spreading and cytoskeletal remodeling. These effects were accompanied by YAP activation and restraint of IKKα-p100/p52 non-canonical NF-κB signaling, leading to downregulation of key osteoclast regulators and effectors and impaired osteoclast fusion and maturation. In an ob/ob diabetic mouse tooth extraction model, AT rapidly mitigated early excessive resorption, promoted collagen matrix deposition and tissue remodeling, and enhanced alveolar ridge preservation. Collectively, these findings demonstrate that biomimetic aligned nanotopographic interfaces can reprogram diabetes-exacerbated resorption-dominant remodeling via interfacial mechanoregulation, thereby providing a biomaterial strategy for alveolar ridge preservation in high-resorption pathological settings.