The craniofacial area consists of several different tissues that include skin, musculoskeletal tissues, salivary glands, teeth and supporting structures such as blood vessels and nerves. Injury to or congenital defect in any of these organs lead not only to severe functional impairment, but also aesthetic problems. Synthetic polymers have been at the center stage in craniofacial therapies enabling tailored, affordable and biocompatible materials over the last century. Despite their superior mechanical and chemical properties, synthetic polymers inherently lack the bioactive information and adaptability provided by natural polymers such as proteins and glycosaminoglycans of the extracellular matrix. Through synthesizing tunable material architectures, implementing protein engineering and peptidomimetics and enabling high-throughput approaches, bioactive hybrid materials can be crafted. In the Extracellular Mimicry Laboratory, we will build new classes of extracellular matrix mimics which have the potential to control cell fate, three-dimensional cellular organization and tissue regeneration and set forth promising strategies towards future craniofacial therapies.