{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:03:39Z","timestamp":1787501019095,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian PON Project\u2013BONE++, Development of Micro and Nanotechnologies for Predictivity, Diagnosis, Therapy and Regenerative Treatments of Pathological Bone and Osteo-Articular Alterations","award":["ARS01_00693"],"award-info":[{"award-number":["ARS01_00693"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells have been widely investigated in the field of regenerative medicine and also used as a model to study the differentiation-induction properties of a variety of biomaterials. This study evaluates the osteoinductive potential of novel hydroxyapatite scaffolds functionalized with a phage-displayed peptide (SC1) selected via biopanning for its similarity to bone matrix proteins. The peptide, identified through sequence alignment as a mimotope of osteonectin (SPARC), was used to functionalize scaffolds. Results from SC1 were gathered at different time points (14, 28 and 46 days) and compared with those from nonfunctionalized hydroxyapatite (HA) scaffolds. In vitro experiments, by seeding human adipose-derived stem cells (hASCs), indicated satisfactory biocompatibility for both types of scaffolds. Histochemical observations showed that SC1, better than HA scaffolds, was able to improve hASC osteogenic differentiation, as evaluated through Alizarin Red staining (showing on average a darker staining of 100%). An increase was also observed, especially at early stages (14 days), for osterix (up to 60% increase) and osteonectin immunoexpression (up to 50% increase). In in vivo experiments, cell-free scaffolds of both types were subcutaneously implanted into the backs of mice and analyzed after 2, 4, 8 and 16 weeks. Also, in this case, SC1 more effectively promoted the osteogenic differentiation of infiltrated resident cells. In particular, increased immunoexpression of osterix and osteonectin (+30% and 35%, respectively) was found already at 2 weeks. It can be concluded that SC1 scaffolds may represent a valuable tool to address critical-sized bone defects.<\/jats:p>","DOI":"10.3390\/ijms26157040","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:44:45Z","timestamp":1753184685000},"page":"7040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hydroxyapatite Scaffold and Bioactive Factor Combination as a Tool to Improve Osteogenesis, In Vitro and In Vivo Experiments Using Phage Display Technology"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-8990","authenticated-orcid":false,"given":"Debora","family":"Lo Furno","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana R.","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6781-6387","authenticated-orcid":false,"given":"Maria Giovanna","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-4154","authenticated-orcid":false,"given":"Giuliana","family":"Mannino","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-5403","authenticated-orcid":false,"given":"Giovanna","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-3675","authenticated-orcid":false,"given":"Rosario","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0810-6121","authenticated-orcid":false,"given":"Simona","family":"D\u2019Aprile","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Salvatorelli","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, Anatomic Pathology, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Magro","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, Anatomic Pathology, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bendoni","sequence":"additional","affiliation":[{"name":"Fin-Ceramica Faenza SPA, Via Granarolo 177\/3, 48018 Faenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dolcini","sequence":"additional","affiliation":[{"name":"Fin-Ceramica Faenza SPA, Via Granarolo 177\/3, 48018 Faenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Zappal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore P. P.","family":"Guglielmino","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Conoci","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"},{"name":"Department of Chemistry \u201cGiacomo Ciamician\u201d, University of Bologna, Via Selmi 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-4696","authenticated-orcid":false,"given":"Rosalba","family":"Parenti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alonzo, M., Primo, F.A., Kumar, S.A., Mudloff, J.A., Dominguez, E., Fregoso, G., Ortiz, N., Weiss, W.M., and Joddar, B. (2021). Bone tissue engineering techniques, advances and scaffolds for treatment of bone defects. Curr. Opin. Biomed. 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