In situ implantable three-dimensional extracellular matrix bioactive composite scaffold for postoperative skin cancer therapy

Abstract Despite drastic improvements in surgical excision techniques, tumor recurrence has remained a significant problem over the past decades. In particular, there are unavoidable factors that include intraoperative tissue defects and trauma-related bacterial infections that can persistently induce tumor recurrence after surgical excision. Here, a novel platform was established with an extracellular matrix (ECM) scaffold that innovatively incorporated photothermal (PTT)/chemodynamic therapy (CDT). A decellularized small intestinal submucosa extracellular matrix (dSIS-ECM) was extracted from porcine small intestine and used to generate a polyporous tissue engineering scaffold. In addition, black phosphorus nanosheets (BPNs) were synchronously assembled by polydopamine (PDA) and Ag nanoparticles (Ag NPs) to fabricate a BPNs-PDA@Ag nanosystem. The as-prepared BPNs-PDA@Ag nanosystem was incorporated into the polyporous dSIS-ECM to establish a three-dimensional bioactive composite scaffold (dSIS-BPNs-PDA@Ag) that exhibited broad-spectrum bactericidal effects (over 99.6%) toward the E. coli and S. aureus. Additionally, the dSIS-BPNs-PDA@Ag composite scaffold not only accelerated the regeneration of infected wounds due to the intrinsic bioactive elements of dSIS but also effectively inhibited tumor recurrence by generating hyperthermia and hydroxyl radicals (•OH), which kill local residual tumor cells at the sites of excised tumors. In brief, this work designed an ingenious “all in one” strategy to achieve the integration of regeneration and therapy for future clinical applications. This strategy aims to simultaneously cause effective damage to residual tumor cells and bacterial infections and accelerate the regeneration of tissue defects for postoperative therapy.