Implantable Sandwich-like Scaffold/Fiber Composite Spatiotemporally Releasing Combretastatin A4 and Doxorubicin for Efficient Inhibition of Postoperative Tumor Recurrence.

Abstract

Tumor recurrence is a critical conundrum in the postoperative therapy, on account of severe bleeding with disseminated tumor cells, residual tumor cells, and the rich nutrient and oxygen supply transported to tumors by the abundant blood vessels. Biodegradable drug-loaded implants, inserted in the resection cavity right away upon the surgery, possess bleeding prevention and efficient chemotherapeutic capabilities, considered to be a promising strategy to efficiently inhibit the recurrence of the solid tumor. Here, we developed a sandwich-like composite consisting of the combretastatin A4 (CA4)-loaded 3D-printed scaffold and doxorubicin (DOX)-loaded electrospun fiber (Scaffold-CA4@Fiber-DOX), presenting hemostatic, chemotherapeutic, and antibacterial potencies. The lyophilized 3D-printed scaffold with a porous structure rapidly absorbed and clotted the blood cells and disseminated tumor cells to prevent bleeding and tumor metastasis. Subsequently, the preferentially released CA4 from the scaffold disrupted the microtubules of the vascular endothelial cell, resulting in vascular deformation and consequent insufficient nutrient supply to the solid tumor. The sustained release of DOX from the sandwiched electrospun fiber dramatically inhibited the peripheral tumor cell proliferation. This all-in-one multifunctional implant system, combining efficient vascular disruption and chemotherapy, provides a promising strategy for postoperative tumor therapy.