{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:32:46Z","timestamp":1762867966954,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T00:00:00Z","timestamp":1572652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>Background: The use of biomaterials is commonplace in dentistry for bone regeneration. The aim of this study was to evaluate the performance of a new alloplastic material for bone repair in critical defects and to evaluate the extent of the inflammatory process. Methods: Forty-five New Zealand rabbits were divided into five groups according to evaluation time (7, 14, 30, 60, 120 days), totaling 180 sites with six-millimeter diameter defects in their tibiae. The defects were filled with alloplastic material consisting of poly (lactide-co-caprolactone), beta-tricalcium phosphate, hydroxyapatite and nano-hydroxyapatite (BTPHP) in three different presentations: paste, block, and membrane. Comparisons were established with reference materials, such as Bio-ossTM, Bio-oss CollagenTM, and Bio-gideTM, respectively. The samples were HE-stained and evaluated for inflammatory infiltrate (scored for intensity from 0 to 3) and the presence of newly formed bone at the periphery of the defects. Results: Greater bone formation was observed for the alloplastic material and equivalent inflammatory intensity for both materials, regardless of evaluation time. At 30 days, part of the synthetic biomaterial, regardless of the presentation, was resorbed. Conclusions: We concluded that this novel alloplastic material showed osteoconductive potential, biocompatibility, low inflammatory response, and gradual resorption, thus an alternative strategy for guided bone regeneration.<\/jats:p>","DOI":"10.3390\/sym11111356","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T04:13:08Z","timestamp":1572840788000},"page":"1356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Histological Evaluation of a New Beta-Tricalcium Phosphate\/Hydroxyapatite\/Poly (1-Lactide-Co-Caprolactone) Composite Biomaterial in the Inflammatory Process and Repair of Critical Bone Defects"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-1185","authenticated-orcid":false,"given":"Elizabeth Ferreira","family":"Martinez","sequence":"first","affiliation":[{"name":"Division of Oral Pathology and Cell Biology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"given":"Ana Elisa Amaro","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"given":"Lucas Novaes","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Division of Oral Pathology and Cell Biology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"given":"Andrea Rodrigues","family":"Esposito","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"given":"Walter Israel Rojas","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"given":"Ana Paula Dias","family":"Demasi","sequence":"additional","affiliation":[{"name":"Division of Oral Pathology and Cell Biology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2777-8640","authenticated-orcid":false,"given":"Fabricio","family":"Passador-Santos","sequence":"additional","affiliation":[{"name":"Division of Oral Pathology and Cell Biology, Faculdade S\u00e3o Leopoldo Mandic, Campinas 13045-755, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1016\/j.msec.2013.04.047","article-title":"Comparison of a xenogeneic and an alloplastic material used indental implants in terms of physico-chemical characteristics and in vivo inflammatory response","volume":"33","author":"Figueiredo","year":"2013","journal-title":"Mater. Sci. Eng. C-Mater. Biol. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/clr.13098","article-title":"Histopathological comparison of healing after maxillary sinus augmentation using xenograft mixed with autogenous bone versus allograft mixed with autogenous bone","volume":"29","year":"2018","journal-title":"Clin. Oral Implants Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jcms.2012.01.002","article-title":"Current trends and future perspectives of bone substitute materials e from space holders to innovative biomaterials","volume":"40","author":"Kolk","year":"2012","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jcms.2013.07.026","article-title":"Simultaneous implant placement and bone grafting with particulate mineralized allograft in sites with buccal wall defects, a three-year follow-up and review of literature","volume":"42","author":"Le","year":"2014","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4161\/biom.22948","article-title":"Biomaterials for periodontal regeneration: A review of ceramics and polymers","volume":"2","author":"Shue","year":"2012","journal-title":"Biomatter"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/01.ID.0000078233.89631.F8","article-title":"Localized maxillary ridge augmentation with a block allograft for dental implant placement: Case reports","volume":"12","author":"Leonetti","year":"2003","journal-title":"Implant Dent."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.archoralbio.2016.01.004","article-title":"Maxillary sinus floor augmentation and dental implant placement using dentin matrix protein-1 gene-modified bon\u00e9 marrow stromal cells mixed with deproteinized boving bone: A comparative study in beagles","volume":"64","author":"Liu","year":"2016","journal-title":"Arch. Oral Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1111\/j.1708-8208.2012.00445.x","article-title":"Slow resorption of anorganic bovine bone by osteoclasts in maxillary sinus augmentation","volume":"15","author":"Mesa","year":"2013","journal-title":"Clin. Implant Dent. Relat. Res."},{"key":"ref_9","first-page":"543","article-title":"Comparison of mineralized cancellous bone allograft (Puros) and anorganic bovine bone matrix (Bio-Oss) for sinus augmentation: Histomorphometry at 26 to 32 weeks after grafting","volume":"26","author":"Froum","year":"2006","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1600-0501.2011.02168.x","article-title":"Maxillary sinus floor augmentation with Bio-Oss or Bio-Oss mixed with autogenous bone as graft: A systematic review","volume":"23","author":"Jensen","year":"2012","journal-title":"Clin. Oral Implants Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/jbm.b.30196","article-title":"Maxillary sinus augmentation with Bio-Oss\u00ae particles: A light, scanning, and transmission electron microscopy study in man","volume":"74","author":"Orsini","year":"2005","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/clr.13144","article-title":"New bone formation after transcrestal sinus floor elevation was influenced by sinus cavity dimensions: A prospective histologic and histomorphometric study","volume":"29","author":"Stacchi","year":"2018","journal-title":"Clin. Oral Implants Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5051\/jpis.2012.42.4.127","article-title":"Clinical evaluation of a biphasic calcium phosphate grafting material in the treatment of human periodontal intrabony defects","volume":"42","author":"Lee","year":"2012","journal-title":"J. Periodontal Implant Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.irbm.2010.04.002","article-title":"Physico-chemical and biological properties of a nano-hydroxyapatite powder synthesized at room temperature","volume":"31","author":"Catros","year":"2010","journal-title":"IRBM"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.matsci.31.1.81","article-title":"Biological Responses to Materials","volume":"31","author":"Anderson","year":"2001","journal-title":"Annu. Rev. Mater. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2334\/josnusd.48.219","article-title":"Physico-chemical characterization and biocompatibility evaluation of hydroxyapatites","volume":"48","author":"Pochapski","year":"2006","journal-title":"J. Oral Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1002\/term.1827","article-title":"Polymeric scaffolds as stem cell carriers in bone repair","volume":"9","author":"Rossi","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.dental.2015.01.006","article-title":"Tissue engineering for bone regeneration and osseointegration in the oral cavity","volume":"31","author":"Pilipchuk","year":"2015","journal-title":"Dent. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/jcpe.13058","article-title":"Bone grafts: Which is the ideal biomaterial?","volume":"46","author":"Haugen","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/978-3-642-03900-3_70","article-title":"Electrically Functionalized Hydroxyapatite and Calcium Phosphate Surfaces to Enhance Immobilization and Proliferation of Osteoblasts In Vitro and Modulate Osteogenesis In Vivo","volume":"25","author":"Dekhtya","year":"2009","journal-title":"IFMBE Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/10255842.2010.534986","article-title":"Mechanics and electrostatics of the interactions between osteoblasts and titanium surface","volume":"14","author":"Kabaso","year":"2011","journal-title":"Comput. Methods Biomech. Biomed. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10856-017-5848-0","article-title":"Effects of negatively and positively charged Ti metal surfaces on ceramic coating adhesion and cell response","volume":"28","author":"Govone","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/jre.12530","article-title":"Degradation pattern of a porcine collagen membrane in an in vivo model of guided bone regeneration","volume":"53","author":"Calciolari","year":"2018","journal-title":"J. Periodontal Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1034\/j.1600-051X.2003.01099.x","article-title":"Deproteinized cancellous bovine bone (Bio-Oss) as bone substitute for sinus floor elevation. A retrospective, histomorphometrical study of five cases","volume":"30","author":"Tadjoedin","year":"2003","journal-title":"J. Clin. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1590\/0103-6440201701206","article-title":"Presence of Cells in Fresh-Frozen Allogeneic Bone Grafts from Different Tissue Banks","volume":"28","author":"Coutinho","year":"2017","journal-title":"Braz. Dent. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/jbm.a.35958","article-title":"The pathology of the foreign body reaction against biomaterials","volume":"105","author":"Klopfleisch","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10561-016-9562-9","article-title":"Homologous transplantation with fresh frozen bone for dental implant placement can induce HLA sensitization: A preliminary study","volume":"17","author":"Pelegrine","year":"2016","journal-title":"Cell Tissue Bank"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10856-007-3134-2","article-title":"In vivo degradation of poly (DTE carbonate) membranes. Analysis of the tissue reactions and mechanical properties","volume":"19","author":"Asikainen","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.actbio.2017.08.044","article-title":"Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration","volume":"66","author":"Huang","year":"2018","journal-title":"Acta Biomater"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/jbm.10163","article-title":"Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering","volume":"61","author":"Li","year":"2002","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/905157","article-title":"In vitro biocompatibility and osteoblast differentiation of an injectable chitosan\/nano-hydroxyapatite\/collagen scaffold","volume":"2012","author":"Chen","year":"2012","journal-title":"J. Nanomater"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/12_2010_50","article-title":"Bioactive polymer\/hydroxyapatite (nano) composites for bone tissue regeneration","volume":"Volume 232","author":"Abe","year":"2010","journal-title":"Advances in Polymer Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/jbm.a.36234","article-title":"Poly (vinylphosphonic acid-co-acrylic acid) hydrogels: The effect of copolymer composition on osteoblast adhesion and proliferation","volume":"106","author":"Dey","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1902\/jop.2015.140378","article-title":"Periodontal regeneration\u2014Intrabony defects: Practical applications from the AAP regeneration workshop","volume":"86","author":"Reynolds","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_35","first-page":"835","article-title":"Bone reactions to anorganic bovine bone (Bio-Oss) used in sinus augmentation procedures: A histologic long-term report of 20 cases in humans","volume":"14","author":"Piattelli","year":"1999","journal-title":"Int. J. Oral Maxillofac. Implants"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1034\/j.1600-0501.2003.140316.x","article-title":"Ten-year follow-up in a maxillary sinus augmentation using anorganic bovine bone (Bio-Oss). A case report with histomorphometric evaluation","volume":"14","author":"Sartori","year":"2003","journal-title":"Clin. Oral Implants Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.dental.2015.03.005","article-title":"Key aspects on the use of bone substitutes for bone regeneration of edentulous ridges","volume":"31","author":"Sanz","year":"2015","journal-title":"Dent. Mater."},{"key":"ref_38","first-page":"69","article-title":"Histologic effect of pure-phase beta-tricalcium phosphate on bone regeneration in human artificial jawbone defects","volume":"23","author":"Trisi","year":"2003","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1600-0501.2005.01257.x","article-title":"Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs","volume":"17","author":"Jensen","year":"2006","journal-title":"Clin. Oral Implants Res."},{"key":"ref_40","first-page":"357","article-title":"Biomaterial resorption rate and healing site morphology of inorganic bovine bone and beta-tricalcium phosphate in the canine: A 24-month longitudinal histologic study and morphometric analysis","volume":"19","author":"Artzi","year":"2004","journal-title":"Int. J. Oral Maxillofac. Implants"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.ijom.2007.07.014","article-title":"Guided bone regeneration at dehiscence-type defects using biphasic hydroxyapatite + beta tricalcium phosphate (Bone Ceramic\u00ae) or a collagen-coated natural bone mineral (BioOss Collagen\u00ae): An immunohistochemical study in dogs","volume":"36","author":"Schwarz","year":"2007","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/jbm.a.30524","article-title":"The effect of hydroxyapatite nanocrystals on microvascular endothelial cell viability and functions","volume":"76","author":"Pezzatini","year":"2006","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/jbm.820281209","article-title":"Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix","volume":"28","author":"Chakkalakal","year":"1994","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1046\/j.0906-6713.2003.03304.x","article-title":"Bone augmentation by means ofbarrier membranes","volume":"33","author":"Hammerle","year":"2003","journal-title":"Periodontol. 2000"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ijom.2007.11.010","article-title":"Alveolar bone regeneration using absorbable poly (L-lactide-co-epsilon-caprolactone)\/beta-tricalcium phosphate membrane and gelatin sponge incorporating basic fibroblast growth factor","volume":"37","author":"Kinoshita","year":"2008","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1002\/jbm.a.35505","article-title":"Cell seeding density is a critical determinant for copolymer scaffolds-induced bone regeneration","volume":"103","author":"Yassin","year":"2015","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1600-0501.2005.01228.x","article-title":"Evaluation of an in situ formed synthetic hydrogel as a biodegradable membrane for guided bone regeneration","volume":"17","author":"Jung","year":"2006","journal-title":"Clin. Oral Implants Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ferracini, R., Mart\u00ednez Herreros, I., Russo, A., Casalini, T., Rossi, F., and Perale, G. (2018). Scaffolds as Structural Tools for Bone-Targeted Drug Delivery. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030122"}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/11\/11\/1356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:31:26Z","timestamp":1760189486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/11\/11\/1356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,2]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["sym11111356"],"URL":"https:\/\/doi.org\/10.3390\/sym11111356","relation":{},"ISSN":["2073-8994"],"issn-type":[{"type":"electronic","value":"2073-8994"}],"subject":[],"published":{"date-parts":[[2019,11,2]]}}}