Calcium-Deficient hydroxyapatite as a bone graft material: From hydrated-layer chemistry to clinical performance

Abstract

Calcium-deficient hydroxyapatite (CDHA) is a widely studied calcium phosphate biomaterial due to its chemical similarity to bone mineral and its relevance as a bone graft substitute. This review presents a comprehensive analysis of CDHA's structure, composition, physico-chemical properties, synthesis methods, and biological performance. Attention is given to the material's multiphasic nature, consisting of a crystalline core and an amorphous hydrated surface layer, and to how this structural-chemical duality governs CDHA's thermal stability, mechanical behavior, solubility, and ion exchange capacity. Various synthesis routes, including aqueous precipitation, hydrolysis, and cementitious reactions, are examined with respect to their impact on particle morphology and clinical applicability. Biological performance is assessed through in vitro and in vivo studies, highlighting CDHA's biocompatibility, osteoconductivity, osteoinductivity, and resorption mechanisms. Challenges such as precise compositional characterization and the dynamic behavior of the hydrated surface layer are addressed, underscoring the need for further research. Overall, CDHA stands out as a promising and versatile material for bone substitution, with significant potential for future developments in regenerative medicine and beyond. STATEMENT OF SIGNIFICANCE: Calcium-deficient hydroxyapatite (CDHA) is widely used as a bone graft substitute, yet its structure, composition, and biological behavior are often misunderstood or inconsistently described. This review provides a focused and chemically rigorous analysis of CDHA as a distinct material class within the Ca-P-O-H system, separating it from ion-substituted or loosely defined "biomimetic" apatites. By critically examining its crystalline core, hydrated surface layer, synthesis pathways, ion-exchange properties, and in vivo performance, we try to clarify long-standing ambiguities regarding its solubility, resorption, and osteoinductive potential. The review highlights the central role of the hydrated layer in governing reactivity and biological response, offering guidance for improved characterization, terminology harmonization, and rational design of next-generation bone graft substitutes.

Keywords: Biomimetic apatite; Bone; Calcium phosphate; Calcium-deficient hydroxyapatite; Hydrated layer; Osteoconduction; Osteoinduction.