Pulsed Electrical Stimulation Enhances Body Fluid Transport for Collagen Biomineralization

Abstract

Mechanical loads from physiologic activities such as walking and running generate bioelectricity in bones. By mimicking bioelectricity, external electrical stimulations have also been used therapeutically to stimulate bone-forming cells and, thus, to promote bone regeneration. However, little is known about the physicochemical mechanism(s) by which electrical stimulations drives calcium phosphate mineralization of collagen. Here, we showed that, during in vitro collagen mineralization in the absence of cells, application of pulsed electrical stimulation significantly enhanced the transport of ionic body fluid components through a micrometer-scale channel (∼100–200 μm gap space between the inner surfaces of tube-like collagen scaffolds and a cathode placed inside the collagen scaffolds). The enhanced transport of ionic precursors increased diffusion of the charged precursors from the channel to the inner collagen surface, where bone mineralization was otherwise restricted. The results indicate that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen, allowing us to better control the spatial distribution of the nanocrystals at the microscale. The findings from this study provide insights into the utilization of electrical stimulation for applications such as facilitating bone-fracture healing and designing better bone-specific biomaterials.

Oxide– and Silicate–Water Interfaces and Their Roles in Technology and the Environment

“…In addition, microbial metabolism induces formation and transformation of Fe-oxides, and these interactions contribute significantly to the global Fe cycle. , Biomineralization also occurs in the oceans on such a large scale that it influences many aspects of seawater chemistry and results in large-scale carbon sequestration in the form of carbonate sediments. Moreover, major classes of tissues, such as bones and teeth, are formed in animals and humans through biomineralization. ,,,,,− …”

“… Whether that matrix is insoluble and provides a scaffold for mineral formation or is soluble and acts to shape mineral products or drive dissolution, it manipulates energetic controls over ion transfer and phase transformation through processes that are inherently interfacial (Figure B,C). , Although few, if any, examples exist for which there is a clear understanding of the physicochemical mechanisms by which bioorganic matrices alter free energy landscapes and kinetic barriers to exert such controls, in vitro studies point towards a number of possibilities, ranging from the purely physical, such as the effects of confinement on mineral phase, shape, and orientation, ,− to chemically-defined processes, including the complexation of ions by highly charged macromolecules, stabilization of hydrated amorphous phases by both proteins and ions, and stereochemical effects that combine lattice matching with chemical reactivity to guide nucleation or modify crystal habits. In addition, living organisms can cause pulsed bioelectricity to trigger biomineralization, and repeated mechanical loading induced by their movements can also facilitate the transport of precursor molecules into confined spaces of organic matrices and direct biomineralization in specific locations with desired functionalities …”

“…833,997 Although few, if any, examples exist for which there is a clear understanding of the physicochemical mechanisms by which bioorganic matrices alter free energy landscapes and kinetic barriers to exert such controls, in vitro studies point towards a number of possibilities, ranging from the purely physical, such as the effects of confinement on mineral phase, shape, and orientation, 833,1116−1122 to chemically-defined processes, including the complexation of ions by highly charged macromolecules, stabilization of hydrated amorphous phases by both proteins and ions, 1109 and stereochemical effects that combine lattice matching with chemical reactivity to guide nucleation or modify crystal habits. In addition, living organisms can cause pulsed bioelectricity to trigger biomineralization, 1108 and repeated mechanical loading induced by their movements can also facilitate the transport of precursor molecules into confined spaces of organic matrices and direct biomineralization in specific locations with desired functionalities. 1107 Overlying these energetic controls and of equal or greater importance are the biological controls that create the local physicochemical environment for biomineralization.…”

“…In addition, recent advances in understanding the dynamics, formation energies, and structure of prenucleation clusters have sharpened our awareness of several knowledge gaps largely driven by the role of the hydration−dehydration reactions, chemical transformations, and phase evolution that accompany nucleation, as well as the impact of surface potential, 1108 whether inherent or applied, on the development of nuclei associated with system complexity. In the case of nonclassical nucleation pathways, the complexities relate to the chemical transformations and phase evolution that accompany nucleation.…”

Microsecond pulse electrical stimulation modulates cell migration

“…4c). It has been shown that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen and drive collagen calcium phosphate mineralization 36 . In addition, cells could mechano-sense matrix stiffness as they could apply contractile forces to fibrillar collagen, and there were reported that cells have durotaxis properties on stiffness gradients surface and migrate faster on harder surfaces 37 .…”