{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:06:32Z","timestamp":1773885992777,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["APVV-20-0184"],"award-info":[{"award-number":["APVV-20-0184"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["1\/0336\/20"],"award-info":[{"award-number":["1\/0336\/20"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant Agency of Ministry of the Education, Science, Research and Sport of the Slovak Republic","award":["APVV-20-0184"],"award-info":[{"award-number":["APVV-20-0184"]}]},{"name":"Grant Agency of Ministry of the Education, Science, Research and Sport of the Slovak Republic","award":["1\/0336\/20"],"award-info":[{"award-number":["1\/0336\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>This study was designed to investigate the effects of hydroxyapatite (HA) ceramic implants (HA cylinders, perforated HA plates, and nonperforated HA plates) on the healing of bone defects, addressing biocompatibility, biodegradability, osteoconductivity, osteoinductivity, and osteointegration with the surrounding bone tissue. The HA ceramic implants were prepared using the tape-casting method, which allows for shape variation in samples after packing HA paste into 3D-printed plastic forms. In vitro, the distribution and morphology of the MC3T3E1 cells grown on the test discs for 2 and 9 days were visualised with a fluorescent live\/dead staining assay. The growth of the cell population was clearly visible on the entire ceramic surfaces and very good osteoblastic cell adhesion and proliferation was observed, with no dead cells detected. A sheep animal model was used to perform in vivo experiments with bone defects created on the metatarsal bones, where histological and immunohistochemical tissue analysis as well as X-ray and CT images were applied. After 6 months, all implants showed excellent biocompatibility with the surrounding bone tissue with no observed signs of inflammatory reaction. The histomorphological findings revealed bone growth immediately over and around the implants, indicating the excellent osteoconductivity of the HA ceramic implants. A number of islands of bone tissue were observed towards the centres of the HA cylinders. The highest degree of biodegradation, bioresorption, and new bone formation was observed in the group in which perforated HA plates were applied. The results of this study suggest that HA cylinders and HA plates may provide a promising material for the functional long-bone-defect reconstruction and further research.<\/jats:p>","DOI":"10.3390\/bioengineering10030291","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T02:03:26Z","timestamp":1677204206000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long-Bone-Regeneration Process in a Sheep Animal Model, Using Hydroxyapatite Ceramics Prepared by Tape-Casting Method"],"prefix":"10.3390","volume":"10","author":[{"given":"Lenka","family":"Kresakova","sequence":"first","affiliation":[{"name":"Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1720-2034","authenticated-orcid":false,"given":"Lubomir","family":"Medvecky","sequence":"additional","affiliation":[{"name":"Division of Functional and Hybrid Systems, Institute of Materials Research of SAS, Watsonova 47, 040 01 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-7180","authenticated-orcid":false,"given":"Katarina","family":"Vdoviakova","sequence":"additional","affiliation":[{"name":"Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maros","family":"Varga","sequence":"additional","affiliation":[{"name":"Hospital AGEL Kosice-Saca, Lucna 57, 040 15 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-7583","authenticated-orcid":false,"given":"J\u00e1n","family":"Danko","sequence":"additional","affiliation":[{"name":"Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Totkovic","sequence":"additional","affiliation":[{"name":"Hospital AGEL Kosice-Saca, Lucna 57, 040 15 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Spakovska","sequence":"additional","affiliation":[{"name":"Hospital AGEL Kosice-Saca, Lucna 57, 040 15 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7296-4034","authenticated-orcid":false,"given":"Marko","family":"Vrzgula","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, Trieda SNP 1, 040 11 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Giretova","sequence":"additional","affiliation":[{"name":"Division of Functional and Hybrid Systems, Institute of Materials Research of SAS, Watsonova 47, 040 01 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaroslav","family":"Briancin","sequence":"additional","affiliation":[{"name":"Institute of Geotechnics SAS, Watsonova 45, 040 01 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-8459","authenticated-orcid":false,"given":"Veronika","family":"\u0160imaiov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Kadasi","sequence":"additional","affiliation":[{"name":"Clinic of Ruminants, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1007\/s10856-014-5240-2","article-title":"Bone substitutes in orthopaedic surgery: From basic science to clinical practice","volume":"25","author":"Campana","year":"2014","journal-title":"J Mater. Sci. Mater. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bone.2016.02.020","article-title":"Inflammation, fracture and bone repair","volume":"86","author":"Loi","year":"2015","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.biomaterials.2018.07.017","article-title":"Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives","volume":"180","author":"Bolander","year":"2018","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"911180","DOI":"10.3389\/fbioe.2022.911180","article-title":"The Osteoinductivity of Calcium Phosphate-Based Biomaterials: A Tight Interaction With Bone Healing","volume":"16","author":"Zhang","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s42247-019-00063-3","article-title":"Bone regeneration with hydroxyapatite-based biomaterials","volume":"3","author":"Bal","year":"2020","journal-title":"Emergent. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s13770-021-00343-2","article-title":"Tissue-Engineered Hydroxyapatite Bone Scaffold Impregnated with Osteoprogenitor Cells Promotes Bone Regeneration in Sheep Model","volume":"18","author":"Bajuri","year":"2021","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1002\/jbm.b.34049","article-title":"Hydroxyapatite\/beta-tricalcium phosphate biphasic ceramics as regenerative material for the repair of complex bone defects","volume":"106","author":"Owen","year":"2018","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s40204-019-00125-z","article-title":"Bone tissue regeneration: Biology, strategies and interface studies","volume":"8","author":"Ansari","year":"2019","journal-title":"Prog. Biomater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40824-018-0149-3","article-title":"Bioactive calcium phosphate materials and applications in bone regeneration","volume":"23","author":"Jeong","year":"2019","journal-title":"Biomater. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1532-849X.2006.00129.x","article-title":"Calcium phosphate cement: Review of mechanical and biological properties","volume":"15","author":"Ambard","year":"2006","journal-title":"J. Prosthodont."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1089\/ten.tec.2016.0361","article-title":"Focus Ion Beam\/Scanning Electron Microscopy Characterization of Osteoclastic Resorption of Calcium Phosphate Substrates","volume":"23","author":"Espanol","year":"2017","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1177\/0391398818771530","article-title":"Purification processes of xenogeneic bone substitutes and their impact on tissue reactions and regeneration","volume":"41","author":"Kavehei","year":"2018","journal-title":"Int. J. Artif. Organs."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2015.02.003","article-title":"Elucidating the Individual Effects of Calcium and Phosphate Ions on hMSCs by Using Composite Materials","volume":"17","author":"Danoux","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5444","DOI":"10.1016\/j.biomaterials.2005.01.072","article-title":"In vivo bone regeneration with injectable calcium phosphate biomaterial: A three-dimensional micro-computed tomographic, biomechanical and SEM study","volume":"26","author":"Gauthier","year":"2005","journal-title":"Biomaterials"},{"key":"ref_15","unstructured":"Ducheyne, P., Healy, K.E., Hutmacher, D.W., Grainger, D.W., and Kirkpatrick, C.J. (2011). Comprehensive Biomaterials, Elsevier. [1st ed.]."},{"key":"ref_16","unstructured":"Graca, M.P.F., and Gavinho, S.R. (2020). Contemporary Topics about Phosphorus in Biology and Materials, IntechOpen. Available online: https:\/\/www.intechopen.com\/books\/contemporary-topics-about-phosphorus-in-biology-and-materials\/calcium-phosphate-cements-in-tissue-engineering."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jab.770020307","article-title":"Bone graft and bone graft substitutes: A review of current technology and applications","volume":"2","author":"Damien","year":"1991","journal-title":"J. Appl. Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijom.2004.06.005","article-title":"The use of hydroxyapatite and autogenous cancellous bone grafts to repair bone defects in rats","volume":"34","author":"Silva","year":"2005","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.bioactmat.2017.05.007","article-title":"Bone grafts and biomaterials substitutes for bone defect repair: A review","volume":"2","author":"Wang","year":"2017","journal-title":"Bioact. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.3390\/ma6093840","article-title":"Calcium Orthophosphate-Based Bioceramics","volume":"6","author":"Dorozhkin","year":"2013","journal-title":"Materials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4742","DOI":"10.1021\/cr800427g","article-title":"Calcium phosphate-based osteoinductive materials","volume":"108","author":"LeGeros","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/00006534-200202000-00032","article-title":"A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: Part I","volume":"109","author":"Gosain","year":"2002","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.actbio.2009.10.050","article-title":"Osteoinduction of hydroxyapatite\/\u03b2-tricalcium phosphate bioceramics in mice with a fractured fibula","volume":"6","author":"Cheng","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13614","DOI":"10.1073\/pnas.1003600107","article-title":"Osteoinductive ceramics as a synthetic alternative to autologous bone grafting","volume":"107","author":"Yuan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1016\/j.biomaterials.2012.04.021","article-title":"The influence of genetic factors on the osteoinductive potential of calcium phosphate ceramics in mice","volume":"33","author":"Barradas","year":"2012","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.msec.2019.03.027","article-title":"Structure Degradation and Strength Changes of Sintered Calcium Phosphate Bone Scaffolds with Different Phase Structures during Simulated Biodegradation In Vitro","volume":"100","author":"Stastny","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.bioactmat.2021.09.024","article-title":"Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants","volume":"11","author":"Zhi","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10047-005-0292-1","article-title":"Bone tissue engineering with porous hydroxyapatite ceramics","volume":"8","author":"Yoshikawa","year":"2005","journal-title":"J. Artif. Organs."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jcis.2013.12.055","article-title":"Nanoscale surface characterization of biphasic calcium phosphate, with comparisons to calcium hydroxyapatite and \u03b2-tricalcium phosphate bioceramics","volume":"420","author":"Samani","year":"2014","journal-title":"J. Colloid Interface Sci."},{"key":"ref_30","first-page":"25","article-title":"Biologic properties of nano-hydroxyapatite: An in vivo study of calvarial defects, ectopic bone formation and bone implantation","volume":"25","author":"Pang","year":"2015","journal-title":"Biomed. Mater. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/jbm.a.31013","article-title":"Development of superporous hydroxyapatites and their examination with a culture of primary rat osteoblasts","volume":"82","author":"Sakamoto","year":"2007","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fendo.2018.00006","article-title":"The impact of type 2 diabetes on bone fracture healing","volume":"9","author":"Marin","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_33","first-page":"9","article-title":"Hydroxyapatite\u2014Past, present, and future in bone regeneration","volume":"7","author":"Kattimani","year":"2016","journal-title":"Bone Tissue Regen. Insights."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/j.actbio.2011.03.019","article-title":"Nanoscale hydroxyapatite particles for bone tissue engineering","volume":"7","author":"Zhou","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19602","DOI":"10.1038\/s41598-019-56124-4","article-title":"Nanosized hydroxyapatite and \u03b2-tricalcium phosphate composite: Physico-chemical, cytotoxicity, morphological properties and in vivo trial","volume":"9","author":"Brum","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s12576-017-0564-6","article-title":"Regeneration of sciatic nerve crush injury by a hydroxyapatite nanoparticle-containing collagen type I hydrogel","volume":"68","author":"Salehi","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10856-021-06591-x","article-title":"In vitro and in vivo biological performance of hydroxyapatite from fish waste","volume":"32","author":"Prado","year":"2021","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_38","first-page":"109","article-title":"Comparative In Vivo Study of Biocompatibility of Apatites Incorporated with 1% Zinc or Lead Ions versus Stoichiometric Hydroxyapatite","volume":"19","author":"Giorno","year":"2014","journal-title":"J. Biomim. Biomater. Biomed. Eng."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"990931","DOI":"10.3389\/fmats.2022.990931","article-title":"Biomaterial-based strategy for bone tumor therapy and bone defect regeneration: An innovative application option","volume":"9","author":"Zhang","year":"2022","journal-title":"Front. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26252","DOI":"10.1039\/C9RA05214C","article-title":"Biomaterials for bone tissue engineering scaffolds: A review","volume":"9","author":"Qu","year":"2019","journal-title":"RSC Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/jbm.b.30876","article-title":"Phase Conversion of Tricalcium Phosphate into Ca-Deficient Apatite During Sintering of Hydroxyapatite\u2013Tricalcium Phosphate Biphasic Ceramics","volume":"84","author":"Kong","year":"2008","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Huang, S.M., Liu, S.M., Chen, W.C., Ko, C.L., Shih, C.J., and Chen, J.C. (2022). Morphological Changes, Antibacterial Activity, and Cytotoxicity Characterization of Hydrothermally Synthesized Metal Ions-Incorporated Nanoapatites for Biomedical Application. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070885"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.actbio.2018.03.007","article-title":"In vitro and in vivo studies on zinc-hydroxyapatite composites as novel biodegradable metal matrix composite for orthopedic applications","volume":"71","author":"Yang","year":"2018","journal-title":"Acta Biomaterialia."},{"key":"ref_44","first-page":"203","article-title":"In vivo study on biocompatibility and bonding strength of hydroxyapatite-20vol%Ti composite with bone tissues in the rabbit","volume":"16","author":"Chu","year":"2006","journal-title":"Biomed. Mater. Eng."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.actbio.2018.11.003","article-title":"Mineralization in Micropores of Calcium Phosphate Scaffolds","volume":"83","author":"Rustom","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_46","first-page":"871","article-title":"Cellular mechanisms of calcium phosphate ceramic degradation","volume":"14","author":"Heymann","year":"1999","journal-title":"Histol. Histopathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/jbm.820170505","article-title":"Biodegradation behavior of various calcium phosphate materials in bone tissue","volume":"17","author":"Klein","year":"1983","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0272-8842(95)00126-3","article-title":"Bioactive materials","volume":"22","author":"Cao","year":"1996","journal-title":"Ceram. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00003086-198807000-00017","article-title":"Porous hydroxyapatite and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits. A comparative histomorphometric and histologic study of bony ingrowth and implant substitution","volume":"232","author":"Eggli","year":"1988","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1302\/2058-5241.3.170056","article-title":"Bioceramics and bone healing","volume":"3","author":"Ginebra","year":"2018","journal-title":"EFORT Open Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/BOT.0000000000000460","article-title":"Bone Grafting: Sourcing, Timing, Strategies, and Alternatives","volume":"29","author":"Egol","year":"2015","journal-title":"J. Orthop. Trauma"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10856-012-4789-x","article-title":"Comparison of mesenchymal stem cell proliferation and differentiation between biomimetic and electrochemical coatings on different topographic surfaces","volume":"24","author":"Hua","year":"2013","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10266-013-0116-3","article-title":"Blood vessels are concentrated within the implant surface concavities: A histologic study in rabbit tibia","volume":"102","author":"Scaran","year":"2014","journal-title":"Odontology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1744-7402.2005.02020.x","article-title":"Bioceramic bone graft substitutes: Influence of porosity and chemistry","volume":"2","author":"Hing","year":"2005","journal-title":"Int. J. Appl. Ceram. Technol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"90","DOI":"10.22203\/eCM.v024a07","article-title":"Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis","volume":"24","author":"Aguirre","year":"2012","journal-title":"Eur. Cells Mater."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Shen, Y., Rahaman, M., Liu, Y., and Huang, Y.W. (2019). Evaluation of Open Hollow Hydroxyapatite Microsphere on Bone Regeneration in Rat Calvarial Defects. bioRxiv.","DOI":"10.1101\/669598"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tanaka, M., Haniu, H., Kamanaka, T., Takizawa, T., Sobajima, A., Yoshida, K., Aoki, K., Okamoto, M., Kato, H., and Saito, N. (2017). Physico-Chemical, In Vitro, and In Vivo Evaluation of a 3D Unidirectional Porous Hydroxyapatite Scaffold for Bone Regeneration. Materials, 10.","DOI":"10.3390\/ma10010033"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/jbm.a.30038","article-title":"Determining relevance of a weightbearing ovine model for bone ingrowth assessment","volume":"69","author":"Willie","year":"2004","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.actbio.2020.03.016","article-title":"Custom-made macroporous bioceramic implants based on triply-periodic minimal surfaces for bone defects in load-bearing sites","volume":"109","author":"Charbonnier","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"153","DOI":"10.36557\/2674-8169.2019v1n7p153-164","article-title":"Evaluation of strontium-containing hydroxyapatite as bone substitute in sheep tibiae","volume":"1","author":"Machado","year":"2019","journal-title":"Braz. J. Implantol. Health Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.2147\/IJN.S238800","article-title":"Electrospun Icariin-Loaded Core-Shell Collagen, Polycaprolactone, Hydroxyapatite Composite Scaffolds for the Repair of Rabbit Tibia Bone Defects","volume":"15","author":"Zhao","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"407","DOI":"10.22203\/eCM.v021a31","article-title":"Osteoinductive biomaterials: Current knowledge of properties, experimental models and biological mechanisms","volume":"21","author":"Barradas","year":"2011","journal-title":"Eur. Cells Mater."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mattod.2015.10.008","article-title":"Calcium phosphates in biomedical applications: Materials for the future?","volume":"19","author":"Habraken","year":"2016","journal-title":"Mater. Today"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.actbio.2019.10.044","article-title":"A method to visually observe the degradation-diffusion-reconstruction behavior of hydroxyapatite in the bone repair process","volume":"101","author":"Li","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/jbm.a.31994","article-title":"Study of hydroxyapatite osteoinductivity with an osteogenic differentiation of mesenchymal stem cells","volume":"89","author":"Lin","year":"2009","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.oceram.2021.100122","article-title":"Ionic substituted hydroxyapatite for bone regeneration applications: A review","volume":"6","author":"Ressler","year":"2021","journal-title":"Open Ceram."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/term.1782","article-title":"Comparative study of the osteogenic ability of four different ceramic constructs in an ectopic large animal model","volume":"10","author":"Viateau","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1089\/ten.2005.11.814","article-title":"Petite, De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model","volume":"11","author":"Oudina","year":"2005","journal-title":"Tissue Eng."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/jor.20352","article-title":"Long-bone critical-size defects treated with tissue-engineered grafts: A study on sheep","volume":"25","author":"Viateau","year":"2007","journal-title":"J. Orthop. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"734486","DOI":"10.3389\/fbioe.2021.734486","article-title":"Bone Regeneration in Load-Bearing Segmental Defects, Guided by Biomorphic, Hierarchically Structured Apatitic Scaffold","volume":"9","author":"Kon","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s002239900583","article-title":"Reconstruction of extensive long-bone defects in sheep using porous hydroxyapatite sponges","volume":"64","author":"Marcacci","year":"1999","journal-title":"Calcif. 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