Targeted Delivery of α‐ketoglutarate to Macrophages in Bone: A Novel Therapeutic Strategy for Improving Fracture Healing in Type 2 Diabetes (Adv. Sci. 23/2025)

Improving Fracture Healing in Type 2 Diabetes In article number 2415667, Jia Li, Wei Lei, Yafei Feng, and co-workers demonstrate that diminished α-ketoglutarate (α-KG) levels impair bone morphogenetic protein 2 (BMP2) secretion in macrophages under type 2 diabetes mellitus (T2DM) conditions. This cover illustration depicts the mechanism of alendronate-modified liposomes designed to specifically target macrophages and deliver α-KG payloads. Through epigenetic reprogramming mediated by α-KG supplementation, macrophages regain their ability to secrete BMP2, thereby promoting fracture healing processes. These findings establish targeted α-KG delivery to macrophages as a novel therapeutic strategy for improving impaired fracture healing in T2DM patients.