Transdermal carbon monoxide delivery.

Overuse injuries or acute trauma in joints often lead to painful tendinopathy, and pharmacological treatment effects are limited. The site of the disease is hard to reach with drugs, both systemically and through the skin. Therapeutic gases may close this gap, as they permeate easier through tissues than conventional small molecules. We present a patch device releasing the anti-inflammatory gas carbon monoxide (CO) through the skin to the subcutaneous tendons and tissues. CO is chemically generated upon device activation and its design maximizes CO exposure to the underlying skin and protects the patient from all side and degradation products. The patch delivered CO successfully through the intact skin, granting lasting, subcutaneous CO exposure for up to 16 h. Furthermore, the released CO induced the proliferation of fibroblasts and the polarization of monocytes into anti-inflammatory M2 macrophages. In conclusion, the CO-releasing device might open an entirely new treatment option against tendinopathies in case of a positive outcome of future in vivo studies.