Abstract :
[en] Alveolar bone deficiency remains one of the main challenges in implant-driven oral rehabilitation.
Calcium-phosphate biomaterials are widely used to restore bone volume prior to or alongside
implant placement. Despite their extensive clinical use, biomaterials are still commonly evaluated
according to their class, origin, or commercial brand rather than according to the physico-
chemical and structural characteristics that govern their biological behavior.
This thesis investigated how the physicochemical, structural, and manufacturing-related
characteristics of calcium-phosphate biomaterials influence biological performance in alveolar
and cranio-maxillofacial bone regeneration. Six complementary studies addressed this question
through a combination of systematic evidence synthesis, controlled in vivo and in vitro
investigations centered on bovine hydroxyapatite, methodological development, and analysis of
emerging next-generation biomaterial concepts. The systematic synthesis demonstrated that
distinct physicochemical parameters influence different regenerative outcomes, with no single
parameter optimizing all outcomes simultaneously and no biomaterial category consistently
outperforming all others. The experimental studies further demonstrated that biomaterials
sharing the same chemistry, origin, and clinical indication may nevertheless exhibit distinct
regenerative behaviors when produced through different manufacturing pathways. These
differences were most pronounced during early healing and could be mechanistically linked
to changes in physicochemical characteristics, protein interactions, and cellular response. In
parallel, a digital-twin workflow based on intraoperative optical scanning was developed to
prospectively define histomorphometric regions of interest, providing a methodology to improve
spatial standardization and reduce cross-study heterogeneity in preclinical bone regeneration
research. Finally, the thesis explored future directions in biomaterial development, including
multiscale structural design, dynamic bioresponsive behavior, computational optimization, and
patient-specific approaches.
Together, the findings of this thesis support a shift in how calcium-phosphate biomaterials are
evaluated. Rather than considering biomaterials primarily according to their class or commercial
designation, the results highlight the importance of the relationship between manufacturing,
physicochemical characteristics and biological behavior. For clinicians, these findings suggest
that differences between biomaterials within the same class may influence regenerative
outcomes and should therefore be considered during material selection. For the scientific
community, the work provides experimental, methodological, and conceptual foundations for
a more biologically grounded approach to biomaterial evaluation and design.
