The Challenge of Healing Wounds in Radiation-Injured Skin

<b>Significance:</b> Wound healing in irradiated skin remains a clinical challenge, with radiation therapy (XRT) resulting in excess collagen deposition and cell death resulting in poor tissue quality. This frequently results in chronic wounds that compromise patient outcomes and quality of life. <b>Recent Advances:</b> Improved understanding of the pathophysiology behind radiation-induced soft tissue injury has led to the development of promising treatments. These include dermal substitutes, placental derivatives, fibronectin, injectable fat-derived and plasma-derived compounds, hyperbaric oxygen, and deferoxamine. <b>Critical Issues:</b> Many traditional approaches to wound healing are often limited by poor tissue quality seen following XRT. A better understanding of mechanisms by which radiation induces these pathological changes may lead to the development of more effective therapeutics. <b>Future Directions:</b> Treatments leveraging recent insights into collateral radiation injury may help to condition tissue to promote healing/regeneration of wounds. Although animal studies and human case reports have been promising, wide-scale clinical studies examining their efficacy are still needed before many of these novel strategies may be adopted to help the millions of patients worldwide suffering from radiation-related cutaneous wounds.