Transdermal bFGF delivery using low-frequency sonophoresis: An innovative potential therapy for osteoradionecrosis of jaws

• ORNJ is irradiated bone exposure without healing for 3 to 6 months, which is difficult to treat.
• Ultrasound is a safe, effective, economical adjunctive therapy in ORNJ.
• bFGF is also important to improve irradiated soft tissue wounds healing.
• bFGF delivery by LFS combines ultrasound with bFGF to synergistically accelerate ORNJ healing.

Osteoradionecrosis of jaws (ORNJ) is a serious complication of radiotherapy for patients with head and neck cancer. As of yet, no universally accepted treatment exists for this chronic pathologic condition. It has been shown that ultrasound is an effective, noninvasive adjunctive therapy in ORNJ, as ultrasound can result in the increase of angiogenesis and bone production, which are essential for ORNJ healing. Recently, low-frequency ultrasound has been demonstrated to enhance the transdermal delivery of macromolecules and hydrophilic drugs (low-frequency sonophoresis, LFS). As a biological macromolecule, basic fibroblast growth factor (bFGF) also has potential osteoinductive and angiogenic properties. Herein, we present a hypothesis that LFS-mediated transdermal bFGF delivery is capable of improving the healing of ORNJ and will be a new effective adjunctive therapy to surgery. This treatment combines low-frequency ultrasound with bFGF to respectively promote vascularly compromised bone and soft tissue wound healing, and is expected to be more effective than ultrasound therapy alone.

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