ABSTRACT Bone substitute biomaterials have become a sine qua non in periodontology and implant dentistry; however, the ideal material choice remains controversial. In this review, we examine natural grafts (autograft, allograft, xenograft) and synthetic grafts (alloplasts, composites, CAD‐CAM personalised materials), comparing them across the triad of osteogenesis, osteoinduction, and osteoconduction. After a thorough presentation of current classification, properties, and mechanisms of action of the various bone grafts, we outline their clinical applications across different indications and discuss future directions in the field. Autografts provide living cells and influential inductive factors, but at the expense of donor‐site morbidity and rapid, unpredictable resorption. Processed allografts and xenografts provide reliable osteoconduction and volumetric stability with reduced inductive potential. Modern alloplasts (β‐TCP, hydroxyapatite, bioactive glass) achieve outcomes comparable to those of natural grafts in selected indications, particularly for space maintenance. Composite strategies, which blend small fractions of autogenous chips with slowly resorbing xenografts or alloplasts and are protected by membranes or meshes, enhance contour stability in sinus floor elevation as well as in lateral and vertical bone augmentation (i.e., guided bone regeneration). In periodontal regeneration of intra‐bony and furcation defects, non‐autogenous bone grafts are added to biologics (e.g., enamel matrix derivatives, platelet concentrates) when space maintenance is needed. Bone substitute materials represent the gold standard for socket preservation, while their adjunctive benefits in peri‐implantitis reconstructive surgery remain limited. CAD–CAM patient‐specific scaffolds and peptide‐modified matrices may enhance fit and handling, but they face challenges related to cost, manufacturing, and regulatory hurdles. The main barriers to translation include batch‐to‐batch variability, regulatory heterogeneity, and limited long‐term safety data. Bioactive glasses are also promising, as they simulate native mineral and do not exhibit unfavourable resorption characteristics, especially when strontium is added or when they are used in combination with platelet concentrates. They, however, remain costly and have long manufacturing times, requiring strict quality control. Cost‐effectiveness remains decisive: indeed, only grafts that offer procedural savings through faster healing and fewer reinterventions are likely to be widely adopted. The future of bone grafts lies in precision biomimetics that integrate intelligent drug delivery, personalised design, and rigorous quality control, promising to extend clinical outcomes beyond the traditional autograft paradigm.
Haugen et al. (2026) studied this question.