<p>Bone regeneration is an intrinsic osteogenic differentiation process during defect healing. Tissue differentiation, a cell-mediated phenomenon, is sensitive to the cellular level bio-mechanical environment, and a few research groups have suggested mechanical regulation of tissue regeneration based on local stress and/or strain as feedback variables. The primary objective of this study was to compare several mechano-regulation schemes for their capabilities to predict bone growth at implant/bone interfaces for a proximally textured femoral stem. A patient-specific finite element (FE) model of an implanted femora after THA having a thin granulation tissue layer has been employed to simulate the course of tissue differentiation using different mechano-regulation schemes proposed by earlier researchers. Initially, a comparison has been made to substantiate a better osseointegration for stem surfaces with proximal surface features. It has been observed that the dilatational measure of stress alone turned out to be ineffectual in predicting tissue differentiation; however, ossification trend predicted solely as a function of deviatoric strain was found to be clinically relevant. The post-surgical mechanobiological simulations considering combined mechano-regulation have predicted fibroplasia (around 70%) and direct bone formation (&lt;5%), whereas cartilaginous tissue formation varied between 5 and 20% over the rehabilitation period, in accordance with clinical findings. The deviatoric part of the strain, coupled with dilatational stress stimulus, led to the most accurate prediction. Nonetheless, all the mechanoregulatory algorithms studied here could forecast the crucial facets of secondary bone healing.</p> Graphical abstract <p></p>