Near-infrared-activatable angiogenic proteinaceous nanomicelles for sequential augmentation of bone repair in periodontal defects.

The highly vascularized architecture of natural bone has inspired sequential augmentation of vascularization and osteogenesis to promote bone tissue regeneration, particularly in periodontal defects characterized by severely diminished bone quantity and quality, often worsened by systemic conditions such as osteoporosis. However, current growth factor delivery systems frequently lack precise control over release profiles and allow limited modification of predetermined kinetics. Herein, near-infrared (NIR) light-activatable angiogenic proteinaceous nanomicelles (NMs) bioengineered from vascular elastin-like polypeptide (VELP) have been proposed to enable rapid angiogenesis and on-demand release of osteoinductive growth factors in a biocompatible, minimally invasive manner. This on-demand release is triggered using a specific NIR stimulation (808 nm, 1.5 W/cm² for 10 min), resulting in approximately 80 % BMP-2 release within 5 h, which can be precisely timed to the optimal healing phase. The potential of bone morphogenetic protein-2 (BMP-2)-loaded VELP NMs to release BMP-2 upon NIR irradiation was validated, demonstrating enhanced osteogenic differentiation and maturation within a three-dimensional microporous scaffold. The findings establish VELP NMs as effective smart nanocarriers for growth factor delivery to support vascularized tissue regeneration. This NIR-activatable delivery system offers a promising strategy for the remotely controlled release of therapeutic cargo in tissue injuries.