IN-SILICO DESIGN OF NANOCOMPOSITE SCAFFOLDS FOR BONE REGENERATION

摘要

The accurate prediction of the evolution of mechanical properties of tissue engineering scaffolds to bridge nonunion bone defects is critical for the bone regenerative technologies to become viable in clinical applications. In addition to the scaffold geometry, the scaffold mechanics needs to be tailored to the patient for an effective outcome. In in vivo conditions, the cell seeded scaffolds degrade as the cells seeded on the scaffolds grow, differentiate and regenerate tissue. A fine balance of degradation and "healing" of the living-non-living construct needs to be achieved to fill the defect. In our research group, clay based nanocomposite materials have been used to regenerate bone that has structure and properties identical to human bone. The scaffolds are made of unnatural-aminoacid intercalated clay, in-situ mineralized hydroxyapatite (HAP) in the clay galleries and a degradable polymer polycaprolactone. These scaffolds are shown to mediate mesenchymal stem cell differentiation to osteoblastic lineages. We have developed a novel computational multiscale approach that spans molecular scale to the macroscale. The model incorporates degradation of nanocomposite bone tissue engineering scaffold system and "healing" as the tissue is regenerated. Realistic molecular models of the nanocomposite material system are created using molecular dynamics. Steered molecular dynamics simulations provide the stress-strain response of the material. The response is introduced into microCT image based 3D finite element models of the scaffolds. Damage mechanics based analytical degradation and healing models capture the evolving scaffold mechanics with time. This in silico approach provides the ability to predict the response of implanted scaffolds over time and also tailor the design of nanocomposite biomaterials and scaffolds with targeted properties for bridging nonunion bone defects for personalized medicine.