Formulations and methods to promote biological processes to form or regenerate new hard tissues such as bones, cartilage, and/or dental tissues are disclosed. The formulation enhances biological activities of a hard tissue growth and differentiation factor characterized by specific and selective upregulation and/or extension of the retention time of the intracellular enzymes and signaling molecules that play important roles to proliferate, differentiate, maturate, and/or mineralize the hard tissue forming cells.