A 3D-Printed Graphene BioFuse Implant for Postsurgical Adjuvant Therapy of Cancer: Proof of Concept in 2D- and 3D-Spheroid Tumor Models.

Abstract

Three-dimensional printing is an emerging technology that is finding its niche applications in diverse fields owing to its flexibility concerning personalization and design. Surgery followed by adjuvant therapy is the standard treatment plan in most cancers from stage I to stage III. Most of the available adjuvant therapies, like chemotherapy, radiation therapy, immunotherapy, hormonal therapy, etc., are associated with severe side effects that considerably reduce the quality of life of patients. In addition, there is always the chance of tumor recurrence or metastasis development followed by surgery. This investigation reports the development of a 3D-printed, biodegradable, laser-responsive implant with a chemo-combined thermal ablating potential for adjuvant therapy of cancer. The 3D-printable ink was developed using poly(l-lactide) and hydroxypropyl methylcellulose as the base polymer, doxorubicin as the chemotherapeutic agent, and reduced graphene oxide as the photothermal ablating agent. The personalized implant released the drug pH-dependently (p value < 0.0001) for an extended period (93.55 ± 1.80% → 28 days). The 3D-printed implant exhibited acceptable biophysical properties (tensile strength: 3.85 ± 0.15 MPa; modulus: 92.37 ± 11.50 MPa; thickness: 110 μm) with laser-responsive hyperthermia (ΔT: 37 ± 0.9 °C → 48.5 ± 1.07 °C; 5 min; 1.5 W/cm2) and inherent biodegradable property (SEM analysis). The 3D-printed implant was evaluated for its therapeutic potential in 2D- and 3D-spheroid tumor models (MDA-MB 231 and SCC 084 2D cells) employing MTT cytotoxicity assay, apoptosis assay, cell cycle analysis, and gene expression analysis. The biomolecular aspects and biomechanics of the 3D-printed BioFuse implant were also evaluated by determining the effect of treatment on the expression levels of HSP1A, Hsp70, BAX, and PTEN. It is advocated that the knowledge developed in this project will significantly assist and advance the science aiming to develop a clinically translatable postsurgical adjuvant therapy for cancer.