Shape memory electrospun scaffolds for cell mechanobiology and bone regenerative applications.

摘要

Tissue engineering scaffolds have traditionally been static physical structures poorly suited to mimick the complex dynamic behavior of in vivo microenvironments. Shape memory polymers (SMPs) may address this limitation. Recent work has achieved two-dimensional cytocompatible SMP substrates, of which the surface topography can be triggered to control cell behaviors. To enable further advances in "smart" functional tissue engineering scaffolds, the goal of this dissertation was to develop a programmable cytocompatible SMP scaffold and further investigate potential applications of the SMP scaffolds.;To achieve this goal, in Chapter 2, synthesis and characterization of a family of polyhedral oligosilsesquioxane (POSS)-containing, polyester-based thermoplastic polyurethanes (TPUs) was investigated, and the effect of caprolactone content and water plasticization on the glass transition temperature of the TPUs was explored. In Chapter 3, a programmable SMP scaffold capable of changing shape and internal architecture under cytocompatible conditions was developed using electrospinning. Cell morphology---cytoskeletal and nuclear alignment---was found to be directed by shape-memory-actuated changes in scaffold shape and internal architecture. Furthermore, cells remained viable and attached before and after scaffold architectural change.;The objective of Chapters 4 to 6 was to explore potential applications of programmable cytocompatible SMP scaffolds in bone regenerative medicine. In Chapter 4, the biomechanical feasibility of self-deploying shape memory polymer fixation---smart sleeve---was evaluated. The in vitro mechanical stabilization of the smart sleeve was compared to intramedullary (IM) nail using a mouse femoral transverse fracture model. The torsional mechanical stability provide by the smart sleeve was comparable to the IM nail; but the bending stability of the smart sleeve was significantly lower than the IM nail. In Chapter 5, the biological functionality of the smart sleeve employed as a supplementary stabilization device was investigated in an in vivo mouse critical-size defect model. Intraoperative deployment of the smart sleeve could be triggered by 45 °C saline irrigation. We found that the presence of the smart sleeve did not interfere with the bone healing process between the allograft and the native bone when compared to the allograft alone group. Finally, in Chapter 6, the deployable effect of the SMP scaffolds on the osteogenic differentiation capacity of human adipose-derived stem cells was evaluated. Successful osteogenic differentiation was demonstrated by the assessments of mineral deposition, alkaline phosphatase activity, and gene expression; no statistical difference was found between the active scaffolds and the static scaffolds.;In this dissertation, programmable cytocompatible electrospun SMP scaffolds are developed and further employed to demonstrate their potential applications in cell mechanobiology and bone regeneration. In Chapter 7, conclusions and future directions are discussed and suggested for each chapter of this dissertation.