MC3T3 infiltration and proliferation in bovine trabecular scaffold regulated by dynamic flow bioreactor and augmented by low-intensity pulsed ultrasound

Abstract

BackgroundLow-intensity pulsed ultrasound (LIPUS) has been used in both basic research and clinical settings for its therapeutic potential in promoting tissue healing. Clinical data has shown that LIPUS can accelerate fresh fracture healing. However, the treatment for aging osteoporosis and non-union is still unclear. In addition, the mechanism of ultrasound promoted bone healing has remained unknown.ObjectiveIt is proposed that noninvasive ultrasound treatment can enhance local fluid flow within the tissue to initiate remodeling and regeneration. The goal of this study was to evaluate the effects of dynamic ultrasound in promoting cellular mechanotransduction within bioengineered organic scaffolds to trigger osteogenesis and mineralization.MethodsThe experiment was designed in two-fold: to evaluate the role of LIPUS on osteoblastic-like (MC3T3) cell proliferation and mineralization in response to acoustic waves, using biomechanical rate-dependent signals in a bioreactor; and, to evaluate the new scaffold experimentation techniques, in order to generate a potential implantable biomaterial for orthopedic tissue regeneration and repair.ResultsLIPUS treatment on MC3T3 cells yielded enhanced cellular mineralization (**p < 0.001) in 3-D scaffolding, but reduced the total cell numbers (*p < 0.05), using Alizarin Red staining and cell counting analyses, respectively, in comparison to the control.ConclusionThis study suggests that LIPUS, if applied at proper frequency and duty cycle, can promote cell mineralization within the 3-D organic scaffold under in vitro setting. The translational component of this experiment seeks to draw a parallel to the potential pre-treatment of scaffolds for implantation before orthopedic surgery, which could prove to greatly benefit the patient in accelerating fracture healing and tissue regeneration.The Translational Potential of this ArticleLIPUS stimulation was critical in contributing to the mechanical signaling transductions that activated bone enhancement parameters in MC3T3 cells regulated by bioreactor, and thus has potential to change how we pretreat scaffolds for orthopedic surgery and noninvasively accelerate healing in the future, e.g., in an extreme condition such as long-term space mission.

Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

“… 62 In addition to tumor ablation, ultrasound was proven to enhance bone regeneration since it could enhance the mRNA level of vascular endothelial growth factor A (VEGF-A) and stimulate cartilage cell proliferation, thus accelerating the maturation of newly formed bone and expediting cell mineralization. 63 , 64 With in-depth research, this technique was extended to the infection field for the clinical treatment of bone defects and severe bacterial infection. 27 , 31 , 65 Crasto et al 66 fabricated novel liposome-rhBMP-2 nanocomplexes that can release rhBMP-2 after exposure to nonthermogenic clinical diagnostic ultrasound.…”

Highly Effective Bone Fusion Induced by the Interbody Cage Made of Calcium Silicate/Polyetheretherketone in a Goat Model

“…In interbody fusion, another critical determinant is the new bone formation around the intervertebral fusion cage. , A bioactive material should have the capacity to stimulate biological response to realize effective osteogenesis. , The regenerative ability of the material could be improved by optimizing composition or incorporating bioactive ions that play a pivotal role in osteogenic process. In our previous study, we demonstrated that the presence of CS incorporated into PEEK could effectively release the bioactive Ca 2+ and Si 4+ ions which exerted a positive influence on the osteogenic differentiation of preosteoblasts in vitro .…”

External Stimuli-Responsive Strategies for Surface Modification of Orthopedic Implants: Killing Bacteria and Enhancing Osteogenesis

“…Although there have been numerous studies on utilizing ultrasound for enhancing antibacterial performance or osteogenic capability of orthopedic implants, most of them have focused solely on single function, either antibacterial ability or osteogenic capacity. − However, it is desirable to investigate the performance of an ultrasound-responsive strategy in enhancing both antibacterial and osteogenic capability of orthopedic implants. Furthermore, the selection of sonosensitizers plays a critical role in achieving targeted and successful treatment.…”