Decoupling collagen and mineral contributions to piezoelectricity in human cortical bone via piezoresponse force microscopy.

Human cortical bone is a hierarchically organized multiphase biological nanocomposite composed primarily of type I collagen fibrils reinforced by mineralized hydroxyapatite. Although bone piezoelectricity has been recognized for decades, the quantitative determination of its effective nanoscale electromechanical coefficient and the relative contributions of organic and mineral phases remain incompletely resolved. In this work, the electromechanical response of human cortical bone was investigated using Piezoresponse Force Microscopy (PFM). Measurements were conducted on intact cortical bone and on specimens subjected to controlled NaOCl treatment to selectively reduce the organic matrix, enabling phase-sensitive comparison. The effective electromechanical response of intact cortical bone was found to lie in the sub-picometer-per-volt range, whereas the mineral-dominated, deproteinized structure exhibited a markedly reduced response approaching the symmetry-limited behavior of centrosymmetric hydroxyapatite, with near-zero effective coefficients under Dual AC Resonance Tracking (DART) conditions (d₃₃,eff = -0.0138 ± 0.0074 pm/V). The inferred piezoelectric coefficient associated with the collagen component was estimated to lie within the range of approximately 0.2-0.4 pm/V, which is in qualitative agreement with previously reported nanoscale measurements of isolated collagen fibrils, although the values obtained here are lower, likely due to differences in experimental conditions, sample preparation, and measurement sensitivity. These results provide quantitative experimental evidence that collagen is the principal contributor to electromechanical coupling in cortical bone and clarify the physical basis of load-induced bioelectric phenomena relevant to bone adaptation and regenerative biomaterials design.