Bioinspired adhesive and tumor microenvironment responsive nanoMOFs assembled 3D-printed scaffold for anti-tumor therapy and bone regeneration

Abstract

Tumor-induced bone loss is the main reason causing bone tumor therapy failure. Rational design of implants with both anti-tumor and bone tissue regeneration functions is urgently needed. This study presents a 3D-printed implant that simultaneously releases anti-cancer drugs and growth factors for anti-tumor therapy and osteogenesis. Such an implant was realized by alternatively assembling polydopamine (PDA)-hybridized nanosized zeolitic imidazolate framework-8 (pZIF-8 nanoMOFs) and PDA-decorated-hydroxyapatite nanoparticles (pHA NPs) on the surfaces of the 3D-printed gelatin-based scaffolds through PDA-assisted layer-by-layer (LbL) assembly strategy. The synthesis of the pZIF-8 nanoMOFs was based on mussel-inspired catechol chemistry, which endowed the nanoMOFs with versatile adhesiveness, high drug loading efficiency, good physiological stability, and tumor environment-sensitive degradability. By using the pZIF-8 nanoMOFs as drug nanocarriers, it was possible to define the distinct spatial distribution and environmental-adaptive release patterns for BMP-2 and cisplatin from the scaffold. In vitro and in vivo studies confirmed that the scaffold possessed good osteoinductivity to induce osteogenic differentiation and to promote new bone formation. By responding to stimuli in the tumor microenvironment, the scaffolds efficiently released cisplatin and inhibited tumor growth. In short, this PDA-hybridized nanoMOF offers a new avenue to functionalize biomaterials with smart and responsive therapeutic ability for diverse biomedical applications.