3D printing of nanoparticle-containing scaffolds for cancer phototherapy, magnetic hyperthermia therapy, and tissue regeneration.

Abstract

Cancer therapies often leave behind significant tissue damage, creating a critical need for new strategies that can both eradicate tumors and simultaneously regenerate the lost tissues. This review explores the integration of nanoparticle-based treatments with three-dimensional (3D) printing as a promising solution. This synergistic approach uses nanoparticle-mediated cancer therapies, such as photothermal therapy (PTT) and magnetic hyperthermia (MHT), which can selectively destroy tumors while also being able to stimulate angiogenesis and upregulate tissue regenerative pathways. Most research in the field has focused on hard tissue applications, namely bone; however, recent outcomes in soft tissues, such as skin and myocardium, indicate broader translational potential. In addition, immunomodulation and gene therapy within scaffolds are emerging directions that hold great promise but remain underexplored. Current limitations are also discussed, including insufficient vascularization, the need for improved preclinical models, reproducibility challenges, scalability, and regulatory barriers. By consolidating current evidence, identifying underdeveloped areas, and outlining future directions, this review provides a comprehensive and up-to-date assessment of nanoparticle-incorporated 3D-printed scaffolds for synergistic cancer therapy and tissue regeneration (TR). Importantly, this review is the first to systematically integrate PTT, MHT, and TR within a unified 3D-printed scaffold platform, offering a distinct perspective that can guide future developments in the field. STATEMENT OF SIGNIFICANCE: This review provides the first comprehensive analysis of 3D-printed scaffolds incorporating nanoparticles for combined cancer phototherapy, magnetic hyperthermia therapy, and tissue regeneration. It establishes an integrative framework linking nanoparticle design, scaffold architecture, and biological response, highlighting how multifunctional systems can simultaneously eradicate tumors and promote tissue repair. Particular attention is given to nanoparticle-matrix interactions that modulate cell adhesion, differentiation, angiogenesis, and immune response, as well as to the influence of bioink composition-including polymeric, ceramic, hydrogel, and metallic systems-on the cellular microenvironment. The Outlook section discusses translational challenges such as vascularization, immunogenicity, scalability, and regulatory pathways, outlining future directions for the development of next-generation multimodal therapeutic scaffolds at the interface of nanomedicine and regenerative bioengineering.