Biomechanically tunable scaffolds for bone tissue regeneration and testbeds of cancer bone metastasis

Abstract

Current challenges in bone regeneration and design of humanoid 3D bone metastases cancer testbeds can be overcome by designing bone-mimetic tissue engineering scaffolds with tunable mechanical and biological properties. This study employs three unnatural amino acids to modify montmorillonite clay (MMT), producing polymer clay nanocomposites (PCNs) to construct 3D bone-mimetic scaffolds. The modification of MMT clay with 5-aminovaleric acid, (±)-2-aminopimelic acid, and 4-(4-Aminophenyl) butyric acid is analyzed through x-ray diffraction (XRD) and fourier-transform infrared spectroscopy (FTIR), revealing changes in the interlayer spacing and functional groups. Molecular modeling elucidates the interaction energies in the amino acid intercalated nanoclays that influence the mechanical properties of the scaffolds. 4-(4-Aminophenyl) butyric acid-modified scaffolds exhibited the highest compressive strength, highlighting the critical influence of molecular interactions on the mechanical properties of the PCN. Despite being a small fraction of the scaffold, the presence and type of amino acids significantly affect the scaffold mechanical properties. Cell viability assays affirm biocompatibility of scaffolds. The amino acids within the nanoclays also impact mineralization on scaffolds seeded with human mesenchymal stem cells (hMSCs). Amino acid type also influences the amount of mineralization in the scaffolds. A sequential culture involving hMSCs and breast cancer cells (MCF-7) on the scaffold mimics breast cancer metastasis to bone. Enhanced mineralization by bone cells in the presence of MCF-7 cells is observed, emphasizing their osteoblastic characteristics. Hence, 3D scaffolds for bone regeneration and bone metastasis cancer testbeds can exhibit tunable mechanical properties and biological responses though a simulation guided choice of unnatural amino acids.