Leveraging the multifunctional nature of citrate in chemistry and inspired by its important biological roles in human tissues, a class of highly versatile and functional citrate-based biomaterials has been developed. Citric acid, historically known as an intermediate in the Krebs cycle, is a multifunctional, nontoxic, readily available, and inexpensive cornerstone monomer used in the design of citrate-based biomaterials. In addition to the convenient citrate chemistry for the syntheses of a number of versatile polymers that may be elastomeric, mechanically strong and tough, injectable, photocrosslinkable, tissue adhesive, bioimaging/biosensing-enabled, and/or electrically conductive, citric acid also presents inherent anti-bacterial, anti-clotting, angiogenic characteristics and modulates cellular energy levels leading to facilitated stem cell differentiation, which make citrate biomaterials ideal for a number of medical applications. We have attained a comprehensive new understanding of the citrate roles on osteo-phenotype progression and identified a new mechanism pertaining to the metabolic regulation of citrate to elevate cell energy status for bone formation, referred to as citrate metabonegenic regulation. This previously unexplored citrate metabonegenic regulation has allowed us to design new biomaterials to meet the dynamic biological, biochemical, and biophysical needs in bone regeneration. In this presentation, a methodology for the design of biomimetic citrate biomaterials and their applications in regenerative engineering, drug delivery, bioimaging and biosensing will be discussed with a focus on orthopedic engineering.