Modulate oxygen-releasing erythroid progenitor cells (EPCs) to promote low oxygen conditions (hypoxia) and enhance bone fracture repair.

Bone fracture repair (or healing) is a complex regenerative process aimed at restoring damaged bone to its pre-injury state. About 5% to 10% of all fractures experience delayed or failed healing during this process. Previous studies have suggested that the initial phase of the repair process is characterized by a pronounced oxygen insufficiency (low oxygen condition, or hypoxia), attributed to the disruption of blood vessels. However, due to methodological limitations, the oxygenation activities in the fracture gap remain poorly understood.

The inventors employed different methods to study tissue oxygenation in the fracture gap. They observed high oxygen concentrations that may impede repair in the local area days after the fracture. To address this, the inventors showed that targeting erythroid progenitor cells (EPCs) and local hemoglobin concentrations promotes hypoxic conditions, thereby enhancing fracture repair.

The inventors designed a novel device to guide the recruitment, enrichment, and differentiation of EPCs, with the additional capability of modulating the function of these cells to influence the oxygen environment in the surrounding tissue. The device consists of a scaffold that incorporates or is coated with two bioactive compositions, providing a versatile platform for potential therapeutic applications in the field of regenerative medicine.

• Modulation of EPCs significantly reduced tissue oxygen, promoted hypoxia, and enhanced fracture repair in the fracture gap (demonstrated by significantly increased osteoprogenitor activation, angiogenesis, and bone formation).
• A potential avenue for exploring new therapeutic approaches for fracture healing.
• Elucidated a previously understudied phenomenon of oxygen levels underlying fracture healing.