Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio‐maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future. Aim Within this narrative review, we discuss possible future biomaterials for bone replacement. Scientific Rationale for Study Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce. Practical Implications In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG. Results We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision‐making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations. Conclusions We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling.

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Cultured PDL cells exposed to EMD increase attachment rate, growth rate and metabolism, and subsequently release several growth factors into the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithelial cell growth however, is inhibited by the same signal. This suggest that EMD favours mesenchymal cell growth over epithelium, and that autocrine growth factors released by PDL cells exposed to EMD contribute to periodontal healing and regeneration in a process mimicking natural root development.