Multifunctional Bioactive Dual‐Layered Nanofibrous Matrix for Effective Breast Cancer Therapy and Enhanced Wound Healing

Abstract Surgical resection is the primary treatment for triple‐negative breast cancer (TNBC). Post‐operative complications, including tumor recurrence and bacterial infections, hinder complete remission and long‐term recovery. To address these challenges, a multifunctional bioactive dual‐layered nanofibrous matrix (MBDL‐NanoMat) featuring adaptive shape control, excellent wound adherence, tunable drug release profiles, and superior biocompatibility for post‐surgical applications is developed. The MBDL‐NanoMat comprises a hydrophilic (HyPhil) layer and a hydrophobic (HyPhob) layer, offering distinct functionalities. The HyPhil layer, electrospun with gelatin and copper peroxide nanoparticles (Cu NPs), rapidly releases Cu NPs to induce anticancer effects through chemodynamic therapy (CDT), ferroptosis, and cuproptosis along with antibacterial action. Near‐infrared laser irradiation enhances therapeutic efficacy through photothermal therapy (PTT). The HyPhob layer ensures prolonged therapeutic effects by releasing therapeutic molecules, such as rapamycin, enabling sustained chemotherapy (CT) and antibacterial activity. This synergistic therapeutic system integrates multiple mechanisms—CT, CDT, PTT, ferroptosis, and cuproptosis—suppressing tumor recurrence and accelerating wound healing. Preclinical results demonstrated enhanced angiogenesis, collagen deposition, and dermal regeneration without systemic safety. In short, the MBDL‐NanoMat platform offers a unique advantage in post‐surgical TNBC care by simultaneously targeting tumor recurrence and facilitating wound healing. Further investigation of this platform can significantly improve oncological and regenerative medicine strategies.