Simulations-Driven Materials Design of Mechanically and Biologically Tuned Tissue Engineering Scaffolds for Bone Regeneration

A computational approach to design novel scaffolds for bone tissue regeneration and cancer bone metastasis testbeds has been used to tune the mechanical properties and biological response of polymer clay nanocomposite-based biomaterials. Molecular dynamics simulations and altered phase theory are used to screen unnatural amino acid modifiers for designing tissue engineering scaffolds with tailored mechanical properties. Three amino acids were identified. The scaffold material is a nanocomposite of polymer (polycapralactone), amino acid-modified nanoclays, and hydroxyapatite mineral. We modify montmorillonite clay (MMT) with three unnatural amino acids: 5-aminovaleric acid, (±)-2-aminopimelic acid, and 4-(4-Aminophenyl) butyric acid. Molecular dynamics simulations and experimental studies reveal that the interaction energies in the amino acid intercalated nanoclays influence the mechanical properties of the scaffolds. The amino acid significantly affects the mechanical properties despite being less than 0.14% of the scaffold composition. The 4-(4-Aminophenyl) butyric acid had the highest attractive interactions with the clay, followed by (±)-2-aminopimelic acid and 5-aminovaleric acid. The mechanical response and the elastic modulus values followed the same pattern. All three composites show good biocompatibility with the human mesenchymal stem cells (hMSCs). The amino acids within the nanoclays also impact mineralization on scaffolds seeded with hMSCs. We observe enhanced mineralization in the presence of human breast cancer cells (MCF-7). The scaffolds containing 5-aminovaleric acid exhibited the highest bone mineralization, followed by (±)-2-aminopimelic acid and 4-(4-Aminophenyl) butyric acid. Thus, the selection of unnatural amino acids, guided by simulations, enables the design of biomechanically tunable 3D scaffolds for bone regeneration and bone metastasis cancer testbeds.