A 3D-Printed Biomaterials-Based Platform to Advance Established Therapy Avenues Against Primary Bone Cancers
59 Pages Posted: 1 Jul 2020 Publication Status: Accepted
Abstract
In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanised primary bone cancer model. First, a bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγnull (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of Osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants' ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a promising therapeutic and diagnostic potential of 3DPDDS in an orthotopic humanised OS tumor model.
Keywords: Primary bone sarcoma, Osteosarcoma, Tissue-engineered humanised bone niche, Humanised microenvironment, 3D-printed drug delivery system, medical grade polycaprolactone, Doxorubicin
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