{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:48:44Z","timestamp":1771274924359,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed of 30% hydroxyapatite (HA) and 70% \u03b2-tricalcium phosphate (\u03b2-TCP). Bone core biopsies were obtained at healing times of 6 months, 9 months, and 12 months. Histological evaluation yielded qualitative and quantitative insights into new bone distribution, while micro-computed tomography (micro-CT) and Raman microspectroscopy (RMS) were employed to assess the three-dimensional architecture and macromolecular composition of the regenerated bone. Micro-CT analysis revealed progressive maturation of the regenerated bone microstructure over time. At 6 months, the apical regenerated area exhibited a significantly higher mineralized volume fraction (58 \u00b1 5%) compared to the basal native bone (44 \u00b1 11%; p = 0.0170), as well as significantly reduced trabecular spacing (Tb.Sp: 187 \u00b1 70 \u00b5m vs. 325 \u00b1 96 \u00b5m; p = 0.0155) and degree of anisotropy (DA: 0.37 \u00b1 0.05 vs. 0.73 \u00b1 0.03; p &lt; 0.0001). By 12 months, the mineralized volume fraction in the regenerated area (53 \u00b1 5%) was statistically comparable to basal bone (44 \u00b1 3%; p &gt; 0.05), while Tb.Sp (211 \u00b1 20 \u00b5m) and DA (0.23 \u00b1 0.09) remained significantly lower (Tb.Sp: 395 \u00b1 41 \u00b5m, p = 0.0041; DA: 0.46 \u00b1 0.04, p = 0.0001), indicating continued structural remodelling and organization. Raman microspectroscopy further revealed dynamic macromolecular changes during healing. Characteristic \u03b2-TCP peaks (e.g., 1315, 1380, 1483 cm\u22121) progressively diminished over time and were completely absent in the regenerated tissue at 12 months, contrasting with their partial presence at 6 months. Simultaneously, increased intensity of collagen-specific bands (e.g., Amide I at 1661 cm\u22121, Amide III at 1250 cm\u22121) and carbonate peaks (1065 cm\u22121) reflected active matrix formation and mineralization. Overall, this case series provides qualitative and quantitative evidence that bone regeneration and integration of BCP granules in sinus augmentation continues beyond 6 months, with ongoing maturation observed up to 12 months post-grafting.<\/jats:p>","DOI":"10.3390\/bioengineering12080848","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T09:25:52Z","timestamp":1754558752000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Healing Kinetics of Sinus Lift Augmentation Using Biphasic Calcium Phosphate Granules: A Case Series in Humans"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-2682","authenticated-orcid":false,"given":"Michele","family":"Furlani","sequence":"first","affiliation":[{"name":"Biomedical Science and Public Health Department, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Notarstefano","sequence":"additional","affiliation":[{"name":"Life and Environmental Sciences Department, Polytechnic University of Marche, 60131 Ancona, Italy"},{"name":"Department of Bioscience and Technology for Agriculture, Food and Environment, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-5236","authenticated-orcid":false,"given":"Nicole","family":"Riberti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2414-7130","authenticated-orcid":false,"given":"Emira","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Medical, Oral and Biotechnological Sciences Department, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 66013 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5886-2186","authenticated-orcid":false,"given":"Tania Vanessa","family":"Pierfelice","sequence":"additional","affiliation":[{"name":"Medical, Oral and Biotechnological Sciences Department, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 66013 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-4674","authenticated-orcid":false,"given":"Carlo","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Dental Sciences, San Raffaele University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-5870","authenticated-orcid":false,"given":"Elisabetta","family":"Giorgini","sequence":"additional","affiliation":[{"name":"Life and Environmental Sciences Department, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Iezzi","sequence":"additional","affiliation":[{"name":"Medical, Oral and Biotechnological Sciences Department, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 66013 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4177-7441","authenticated-orcid":false,"given":"Alessandra","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Odontostomatologic and Specialized Clinical Sciences Department, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gul, S.S. (2024). Prevalence and Severity of Circumferential Alveolar Bone Loss Using CBCT Images: A Retrospective Study of 20,620 Surfaces of 5155 Teeth. Diagnostics, 14.","DOI":"10.3390\/diagnostics14050507"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saleh, M.H.A., Sabri, H., Di Pietro, N., Comuzzi, L., Geurs, N.C., Bou Semaan, L., and Piattelli, A. (2025). 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