Enhanced Osteogenic Differentiation of Human Mesenchymal Stem Cells Using Microbubbles and Low Intensity Pulsed Ultrasound on 3D Printed Scaffolds (original) (raw)

2018, Advanced Biosystems

The current treatment options for bone injuries or diseases requiring surgical interventions are autografts, allografts, and artificial implantations. All suffer from significant shortcomings, e.g., insufficient donor tissue availability for autografts, risk of potential immunological rejection for allografts, and lack of proper integration with host tissues, and therefore, multiple surgeries for artificial implantation. [2,3] With increasing incidence of these disorders, alternative strategies for bone tissue repair and regeneration are desirable. Tissue engineering provides a promising tool for tissue repair and generation by growing tissues directly from cells in a bio-mimicking environment by providing a biocompatible scaffold with suitable growth factors and mechanical cues. [4] Human mesenchymal stem cells (hMSCs) have been widely investigated as a potential cell source for bone tissue engineering. [5] The advantage of the hMSCs lies in their ability to differentiate into a variety of cell types, such as osteoblasts, chondrocytes, or adipocytes when exposed to proper environmental and chemical factors. [6,7] 3D printing has emerged as a novel means for constructing a proper environment and patient injury-specific scaffolds for replacements and grafts. [7,8] The scaffolds can be printed from biodegradable materials using computer-assisted design (CAD) packages using CT or MRI images of the injury site. 3D printed structures with controllable pore sizes could also be custom designed to mimic the in vivo microenvironment, where seeded stem cells would grow, proliferate, and differentiate into desired tissues. These constructs would be implanted into the injury sites and integrated with the host tissue as the scaffold material degrades. A number of external factors such as ultrasound, [9-11] electromagnetic fields, [12] bone growth factors (bone morphogenic protein), [13] and medicines (Alendronate) [14] have been known to improve and promote bone cell growth and fracture healing. Traditionally, ultrasound has been utilized as a diagnostic modality. However, low intensity pulsed ultrasound (LIPUS)intensities less than 100 mW cm −2 and frequencies between 0.75 and 1.5 MHz-has been known to have therapeutic potentials [15] and has been approved for bone fracture healing in the United States by the Food and Drug Administration (FDA). It