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Cementum is a mineralized tissue that forms part of the insertion periodontium and serves to fix the teeth to the alveolar bone. In addition, it acts as a reservoir of different growth and differentiation factors, which regulate the biology of the teeth. Cementogenesis is a complex process that is still under investigation and involves different factors, including dentin sialophosphoprotein (DSPP). In this work we studied the role of surface microtopography in the differentiation of human dental pulp stem cells (hDPSCs) into cementoid-like secreting cells. We cultured hDPSCs on decellularized dental scaffolds on either dentin or cementum surfaces. Cell morphology was evaluated by light and electron microscopy. We also evaluated the DSPP expression by immunohistochemistry. The hDPSCs that was cultured on surfaces with accessible dentinal tubules acquired an odontoblastic phenotype and emitted characteristic processes within the dentinal tubules. These cells synthesized the matrix components of a characteristic reticular connective tissue, with fine collagen fibers and DSPP deposits. The hDPSCs that was cultured on cementum surfaces generated a well-organized tissue consisting of layers of secretory cells and dense fibrous connective tissue with thick bundles of collagen fibers perpendicular to the scaffold surface. Intra- and intercellular deposits of DSPP were also observed. The results presented here reinforce the potential for hDPSCs to differentiate in vitro into cells that secrete a cementoid-like matrix in response to the physical stimuli related to the microtopography of contact surfaces. We also highlight the role of DSPP as a component of the newly formed matrix.<\/jats:p>","DOI":"10.3390\/ijms232415588","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T01:51:26Z","timestamp":1670550686000},"page":"15588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Human Dental Pulp Stem Cells Differentiate into Cementoid-Like-Secreting Cells on Decellularized Teeth Scaffolds"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-7983","authenticated-orcid":false,"given":"Manuel","family":"Mata","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"INCLIVA Biomedical Research Institute, 46010 Valencia, Spain"},{"name":"Biomedical Research Networking Center of Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Peydr\u00f3","sequence":"additional","affiliation":[{"name":"Facultad de Odontolog\u00eda, Universidad Europea de Valencia, Passeig de l\u2019Albereda, 7, 46010 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Javier Mart\u00edn","family":"de Llano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"INCLIVA Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-2979","authenticated-orcid":false,"given":"Mar\u00eda","family":"Sancho-Tello","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"INCLIVA Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Carda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"INCLIVA Biomedical Research Institute, 46010 Valencia, Spain"},{"name":"Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicina (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cvsm.2005.03.002","article-title":"Management of periodontal disease: Understanding the options","volume":"35","author":"Harvey","year":"2005","journal-title":"Vet. 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