{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:50:42Z","timestamp":1788601842826,"version":"build-2803163510"},"reference-count":90,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration.<\/jats:p>","DOI":"10.3390\/ijms22073588","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"3588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ex Vivo and In Vivo Analyses of Novel 3D-Printed Bone Substitute Scaffolds Incorporating Biphasic Calcium Phosphate Granules for Bone Regeneration"],"prefix":"10.3390","volume":"22","author":[{"given":"Franciska","family":"Oberdiek","sequence":"first","affiliation":[{"name":"ScientiFY GmbH, 15806 Zossen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Ivan","family":"Vargas","sequence":"additional","affiliation":[{"name":"Escuela T\u00e9cnica Superior de Ingenieros Industriales, Universidad Polit\u00e9cnica de Madrid, Calle Jos\u00e9 Gutierrez Abascal, 2, 28006 Madrid, Spain"},{"name":"REGEMAT 3D, Avenida del conocimiento 41, A-111, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3620-7199","authenticated-orcid":false,"given":"Patrick","family":"Rider","sequence":"additional","affiliation":[{"name":"ScientiFY GmbH, 15806 Zossen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milijana","family":"Batinic","sequence":"additional","affiliation":[{"name":"Research Department, BerlinAnalytix GmbH, 12109 Berlin, Germany"},{"name":"Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"G\u00f6rke","sequence":"additional","affiliation":[{"name":"Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-0684","authenticated-orcid":false,"given":"Milena","family":"Radenkovi\u0107","sequence":"additional","affiliation":[{"name":"Scientific Research Center for Biomedicine, Department for Cell and Tissue Engineering, Faculty of Medicine, University of Ni\u0161, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2411-9802","authenticated-orcid":false,"given":"Stevo","family":"Najman","sequence":"additional","affiliation":[{"name":"Scientific Research Center for Biomedicine, Department for Cell and Tissue Engineering, Faculty of Medicine, University of Ni\u0161, 18000 Ni\u0161, Serbia"},{"name":"Department of Biology and Human Genetics, Faculty of Medicine, University of Ni\u0161, 18000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-5186","authenticated-orcid":false,"given":"Jose Manuel","family":"Baena","sequence":"additional","affiliation":[{"name":"REGEMAT 3D, Avenida del conocimiento 41, A-111, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Jung","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-1347","authenticated-orcid":false,"given":"Mike","family":"Barbeck","sequence":"additional","affiliation":[{"name":"Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Introduction to the challenges of bone repair","volume":"2","author":"Pawelec","year":"2019","journal-title":"Bone Repair Biomater."},{"key":"ref_2","first-page":"83","article-title":"Bone regeneration strategies with bone marrow stromal cells in orthopaedic surgery","volume":"64","author":"Stanovici","year":"2016","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1302\/0301-620X.89B5.19039","article-title":"Bone allografts-What they can offer and what they cannot","volume":"89-B","author":"Delloye","year":"2007","journal-title":"J. Bone Jt. Surg."},{"key":"ref_4","first-page":"194","article-title":"A clinical and histologic examination in humans of the osseous response to implanted natural bone mineral","volume":"12","author":"Skoglund","year":"1997","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1016\/j.biomaterials.2004.09.035","article-title":"A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation","volume":"26","author":"Arinzeh","year":"2005","journal-title":"Biomaterials"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","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_7","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1111\/clr.12983","article-title":"Monophasic \u00df-TCP vs. biphasic HA\/\u00df-TCP in two-stage sinus floor augmentation procedures\u2013a prospective randomized clinical trial","volume":"28","author":"Jelusic","year":"2017","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1016\/j.biomaterials.2005.02.002","article-title":"Porosity of 3D biomaterial scaffolds and osteogenesis","volume":"26","author":"Karageorgiou","year":"2005","journal-title":"Biomaterials"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1016\/j.actbio.2010.07.006","article-title":"Influence of \u03b2-tricalcium phosphate granule size and morphology on tissue reaction in vivo","volume":"6","author":"Ghanaati","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.21823\/2311-2905-2017-23-4-92-100","article-title":"Allogenic Bone Grafting Materials-Update of the Current Scientific Status","volume":"23","author":"Schnettler","year":"2018","journal-title":"Traumatol. Orthop. Russ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12938-016-0236-4","article-title":"3D-printing techniques in a medical setting: A systematic literature review","volume":"15","author":"Tack","year":"2016","journal-title":"Biomed. Eng. Online"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Klocke, F. (2015). Fertigungsverfahren 5-Gei\u00dfen, Pulvermetallurgie, Additive Manufacturing, Springer. [4th ed.].","DOI":"10.1007\/978-3-540-69512-7"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1039\/C3LC50634G","article-title":"Light-assisted direct-write of 3D functional biomaterials","volume":"14","author":"Hribar","year":"2014","journal-title":"Lab Chip"},{"key":"ref_14","unstructured":"H\u00e4nel, T. (2008). Technologieentwicklung f\u00fcr die Herstellung patientenindividueller Knochenaufbauimplantate aus \u00df-Tricalciumphosphat durch 3D-Printing, Technische Universit\u00e4t Chemnitz."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rider, P., Ka\u010darevi\u0107, \u017d.P., Alkildani, S., Retnasingh, S., Schnettler, R., and Barbeck, M. (2018). Additive Manufacturing for Guided Bone Regeneration: A Perspective for Alveolar Ridge Augmentation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113308"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0928-4931(02)00010-3","article-title":"Fabrication of 3D chitosan-hydroxyapatite scaffolds using a robotic dispensing system","volume":"20","author":"Ang","year":"2002","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.compositesb.2017.08.021","article-title":"Investigations for mechanical properties of Hap, PVC and PP based 3D porous structures obtained through biocompatible FDM filaments","volume":"132","author":"Sharma","year":"2018","journal-title":"Compos. Part B Eng."},{"key":"ref_18","first-page":"196","article-title":"3D printing of HA\/PCL composite tissue engineering scaffolds","volume":"2","author":"Jiao","year":"2019","journal-title":"Adv. Ind. Eng. Polym. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1108\/13552541211272045","article-title":"Suitability of PLA\/TCP for fused deposition modeling","volume":"18","author":"Drummer","year":"2012","journal-title":"Rapid Prototyp. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/1748-605X\/ab388d","article-title":"3D printed porous PLA\/nHA composite scaffolds with enhanced osteogenesis and osteoconductivity in vivo for bone regeneration","volume":"14","author":"Chen","year":"2019","journal-title":"Biomed. Mater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1007\/s10856-012-4761-9","article-title":"Stimulation of healing within a rabbit calvarial defect by a PCL\/ PLGA scaffold blended with TCP using solid freeform fabrication technology","volume":"23","author":"Shim","year":"2012","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1016.e1","DOI":"10.1016\/j.joms.2015.01.021","article-title":"Tissue-engineered bone with 3-dimensionally printed \u03b2-tricalcium phosphate and polycaprolactone scaffolds and early implantation: An in vivo pilot study in a porcine mandible model","volume":"73","author":"Konopnicki","year":"2015","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1557\/jmr.2018.112","article-title":"Systematic characterization of 3D-printed PCL\/\u03b2-TCP scaffolds for biomedical devices and bone tissue engineering: Influence of composition and porosity","volume":"33","author":"Bruyas","year":"2018","journal-title":"J. Mater. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.mattod.2015.01.019","article-title":"Biomaterial based modulation of macrophage polarization: A review and suggested design principles","volume":"18","author":"Sridharan","year":"2015","journal-title":"Mater. Today"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5114","DOI":"10.1016\/j.biomaterials.2007.07.010","article-title":"Phenotypic Dichotomies in the Foreign Body Reaction","volume":"28","author":"Anderson","year":"2007","journal-title":"Biomaterials"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Korzinskas, T., Jung, O., Smeets, R., Stojanovic, S., Najman, S., Glenske, K., Hahn, M., Wenisch, S., Schnettler, R., and Barbeck, M. (2018). In vivo analysis of the biocompatibility and macrophage response of a non-resorbable PTFE membrane for guided bone regeneration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102952"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/intimm\/dxy054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.21873\/invivo.12148","article-title":"Specialized Histological and Histomorphometrical Analytical Methods for Biocompatibility Testing of Biomaterials for Maxillofacial Surgery in (Pre-) Clinical Studies","volume":"34","author":"Lindner","year":"2020","journal-title":"In Vivo"},{"key":"ref_30","first-page":"253","article-title":"In vivo biocompatibility and degradation of novel Polycaprolactone-Biphasic Calcium phosphate scaffolds used as a bone substitute","volume":"29","author":"Thuaksuban","year":"2018","journal-title":"Biomed. Mater. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.msec.2006.05.006","article-title":"In vitro degradation of novel bioactive polycaprolactone-20% tricalcium phosphate composite scaffolds for bone engineering","volume":"27","author":"Lei","year":"2007","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10856-017-5883-x","article-title":"Assessment of bone regeneration of a tissue-engineered bone complex using human dental pulp stem cells\/poly(\u03b5-caprolactone)-biphasic calcium phosphate scaffold constructs in rabbit calvarial defects","volume":"28","author":"Wongsupa","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.progpolymsci.2007.05.017","article-title":"Biodegradable polymers as biomaterials","volume":"32","author":"Nair","year":"2007","journal-title":"Prog. Polym. Sci."},{"key":"ref_34","first-page":"4197","article-title":"Selective laser sintering fabrication of nano-hydroxyapatite\/poly-\u03b5-caprolactone scaffolds for bone tissue engineering applications","volume":"8","author":"Xia","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.joms.2011.07.029","article-title":"Three-dimensionally printed polycaprolactone and \u03b2-tricalcium phosphate scaffolds for bone tissue engineering: An in vitro study","volume":"70","author":"Sharaf","year":"2012","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_36","unstructured":"Mark, H.F. (2017). Polycaprolactone: Synthesis, Properties, and Applications. Encyclopedia of Polymer Science and Technology, John Wiley & Sons, Inc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jobcr.2019.10.003","article-title":"Polycaprolactone as biomaterial for bone scaffolds: Review of literature","volume":"10","author":"Dwivedi","year":"2020","journal-title":"J. Oral Biol. Craniofacial. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/1748-6041\/7\/1\/015005","article-title":"The chemical composition of synthetic bone substitutes influences tissue reactions in vivo: Histological and histomorphometrical analysis of the cellular inflammatory response to hydroxyapatite, beta-tricalcium phosphate and biphasic calcium phosphate cer","volume":"7","author":"Ghanaati","year":"2012","journal-title":"Biomed. Mater."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"228","DOI":"10.15644\/asc49\/3\/5","article-title":"Measurements of Implant Stability Following Sinus Lift: A Pilot Clinical Study","volume":"49","author":"Tosum","year":"2015","journal-title":"Acta Stomatol. Croat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1007\/s00784-019-03092-8","article-title":"Alveolar crest contour changes after guided bone regeneration using different biomaterials: An experimental in vivo investigation","volume":"24","author":"Luengo","year":"2020","journal-title":"Clin. Oral Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nature02388","article-title":"Designing materials for biology and medicine","volume":"428","author":"Langer","year":"2004","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1590\/S0366-69132012000400011","article-title":"A biodegradable porous composite scaffold of PCL\/BCP containing Ang-(1-7) for bone tissue engineering","volume":"58","author":"Macedo","year":"2012","journal-title":"Ceramica"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/jbm.a.30528","article-title":"Poly-\u03b5-caprolactone\/hydroxyapatite composites for bone regeneration: In vitro characterization and human osteoblast response","volume":"76","author":"Causa","year":"2006","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1177\/0885328216633890","article-title":"Physical characteristics and biocompatibility of the polycaprolactone-biphasic calcium phosphate scaffolds fabricated using the modified melt stretching and multilayer deposition","volume":"30","author":"Thuaksuban","year":"2016","journal-title":"J. Biomater. Appl."},{"key":"ref_46","first-page":"317","article-title":"Bone regeneration: Molecular and cellular interactions with calcium phosphate ceramics","volume":"1","year":"2006","journal-title":"Int. J. Nanomed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/jbm.a.36006","article-title":"Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells\u2014New insights into the material-mediated healing process","volume":"105","author":"Barbeck","year":"2017","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_48","first-page":"5","article-title":"Biomaterial biocompatibility and the macrophage","volume":"5","author":"Anderson","year":"1984","journal-title":"Biomater. Silver Jubil. Compend."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1016\/j.biomaterials.2012.02.034","article-title":"Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine","volume":"33","author":"Brown","year":"2012","journal-title":"Biomaterials"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1089\/ten.2006.12.1955","article-title":"Cellular and Molecular Dynamics in the Foreign Body Reaction","volume":"12","author":"Luttikhuizen","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_51","first-page":"1","article-title":"Multinucleated giant cells within the in vivo implantation bed of a collagen-based biomaterial determine its degradation pattern","volume":"8","author":"Tanneberger","year":"2020","journal-title":"Clin. Oral Investig."},{"key":"ref_52","first-page":"BR24","article-title":"Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: An experimental study in rabbits","volume":"16","author":"Athanasiou","year":"2010","journal-title":"Med. Sci. Monit."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1615\/CritRevBiomedEng.v40.i5.10","article-title":"Bone tissue engineering: Recent advances and challenges","volume":"40","author":"Amini","year":"2012","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.1089\/ten.tea.2010.0148","article-title":"The correlation between the internal structure and vascularization of controllable porous bioceramic materials in vivo: A quantitative study","volume":"16","author":"Bai","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/ten.tec.2010.0072","article-title":"Macroporous hydrogel scaffolds and their characterization by optical coherence tomography","volume":"17","author":"Chen","year":"2010","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1016\/j.biomaterials.2003.10.086","article-title":"Microcellular polyHIPE polymer supports osteoblast growth and bone formation in vitro","volume":"25","author":"Akay","year":"2004","journal-title":"Biomaterials"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s10856-006-0073-2","article-title":"Development of a new calcium phosphate powder-binder system for the 3D printing of patient specific implants","volume":"18","author":"Khalyfa","year":"2007","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.mattod.2013.11.017","article-title":"Bone tissue engineering using 3D printing","volume":"16","author":"Bose","year":"2013","journal-title":"Mater. Today"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/jerd.12388","article-title":"Treatment of a bilaterally severely resorbed posterior mandible due to early tooth loss by Guided Bone Regeneration using customized allogeneic bone blocks: A case report with 24 months follow-up data","volume":"30","author":"Blume","year":"2018","journal-title":"J. Esthet. Restor. Dent."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/jerd.12454","article-title":"Bilateral maxillary augmentation using CAD\/CAM manufactured allogenic bone blocks for restoration of congenitally missing teeth: A case report","volume":"31","author":"Blume","year":"2019","journal-title":"J. Esthet. Restor. Dent."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/ID.0000000000000023","article-title":"Posterior atrophic mandible rehabilitation with onlay allograft created with cad-cam procedure: A case report","volume":"23","author":"Jacotti","year":"2014","journal-title":"Implant Dent."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/rb\/rbv025","article-title":"Comparison of bone regeneration in alveolar bone of dogs on mineralized collagen grafts with two composition ratios of nano-hydroxyapatite and collagen","volume":"3","author":"Wang","year":"2016","journal-title":"Regen. Biomater."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.carbpol.2009.09.001","article-title":"Optimization of mechanical properties of thermoplastic starch\/clay nanocomposites","volume":"79","author":"Navarchian","year":"2010","journal-title":"Carbohydr. Polym."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsamd.2020.01.007","article-title":"Porous scaffolds for bone regeneration","volume":"5","author":"Abbasi","year":"2020","journal-title":"J. Sci. Adv. Mater. Devices"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1115\/1.4029176","article-title":"Biomechanics and Mechanobiology of Trabecular Bone: A Review","volume":"137","author":"Oftadeh","year":"2015","journal-title":"J. Biomech. Eng."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S0278-2391(99)90437-8","article-title":"Mechanical Properties of Trabecular in the Human Mandible: Implications Dental Implant Treatment Planning and Surgical Placement","volume":"57","author":"Misch","year":"1999","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4103\/0253-7613.132207","article-title":"Noninvasive measurement of systolic blood pressure in rats: A novel technique","volume":"46","author":"Gangwar","year":"2014","journal-title":"Indian J. Pharmacol."},{"key":"ref_69","first-page":"208","article-title":"Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA\/bioglass components\u2013Guidance of the inflammatory response as basis for osteochondral regeneration","volume":"2","author":"Barbeck","year":"2017","journal-title":"Bioact. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/jbm.a.35579","article-title":"Heterogeneity of biomaterial-induced multinucleated giant cells: Possible importance for the regeneration process?","volume":"104","author":"Barbeck","year":"2016","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"055007","DOI":"10.1088\/1748-6041\/10\/5\/055007","article-title":"Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization","volume":"10","author":"Barbeck","year":"2015","journal-title":"Biomed. Mater."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.1563\/aaid-joi-D-14-00168","article-title":"High-Temperature sintering of xenogeneic bone substitutes leads to increased multinucleated giant cell formation: In vivo and preliminary clinical results","volume":"41","author":"Barbeck","year":"2015","journal-title":"J. Oral Implantol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1563\/aaid-joi-D-14-00155","article-title":"Porcine dermis and pericardium-based, non cross-linked materials induce multinucleated giant cells after their in vivo implantation: A physiological reaction?","volume":"41","author":"Barbeck","year":"2015","journal-title":"J. Oral Implantol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.yexmp.2005.06.008","article-title":"Multinucleated giant cell formation exhibits features of phagocytosis with participation of the endoplasmic reticulum","volume":"79","author":"McNally","year":"2005","journal-title":"Exp. Mol. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"636","DOI":"10.11607\/jomi.6026","article-title":"Injectable Bone Substitute Material on the Basis of \u00df-TCP and Hyaluronan Achieves Complete Bone Regeneration While Undergoing Nearly Complete Degradation","volume":"33","author":"Lorenz","year":"2018","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ijom.2006.03.017","article-title":"Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb\u00ae) for bone regeneration in the reconstructive surgery of the jaws","volume":"35","author":"Horch","year":"2006","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1258\/la.2010.010085","article-title":"Rodent models in bone-related research: The relevance of calvarial defects in the assessment of bone regeneration strategies","volume":"45","author":"Gomes","year":"2011","journal-title":"Lab Anim."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1038\/nprot.2012.113","article-title":"Evaluation of bone regeneration using the rat critical size calvarial defect","volume":"7","author":"Spicer","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/jre.12692","article-title":"Guided tissue regeneration of intrabony defects with perforated barrier membranes, simvastatin, and EDTA root surface modification: A clinical and biochemical study","volume":"55","author":"Issa","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Guvendiren, M., and Serpooshan, V. (2020). 3D Printing for Tissue Engineering and Regenerative Medicine, MDPI AG.","DOI":"10.3390\/mi11040366"},{"key":"ref_81","first-page":"77","article-title":"Nanofibrillated chitosan\/polycaprolactone bionanocomposite scaffold with improved tensile strength and cellular behavior","volume":"5","author":"Fadaie","year":"2018","journal-title":"Nanomed. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1741-7015-10-81","article-title":"The role of barrier membranes for guided bone regeneration and restoration of large bone defects: Current experimental and clinical evidence","volume":"10","author":"Dimitriou","year":"2012","journal-title":"BMC Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/1535370218821128","article-title":"Volume-by-volume bioprinting of chondrocytes-alginate bioinks in high temperature thermoplastic scaffolds for cartilage regeneration","volume":"244","author":"Baena","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_84","unstructured":"International Organization for Standardization (2007). ISO 844:2007 (E): Rigid Cellular Plastics\u2014Determination of Compression Properties, International Organization for Standardization."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal research: Reporting in vivo experiments: The ARRIVE guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1590\/1678-775720130316","article-title":"Non-cross-linked collagen type I\/III materials enhance cell proliferation: In vitro and in vivo evidence","volume":"22","author":"Willershausen","year":"2014","journal-title":"J. Appl. Oral Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1563\/aaid-joi-D-14-00274","article-title":"Porcine dermis-derived collagen membranes induce implantation bed vascularization via multinucleated giant cells: A physiological reaction?","volume":"41","author":"Barbeck","year":"2015","journal-title":"J. Oral Implantol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4103\/2231-0746.147106","article-title":"Induction of multinucleated giant cells in response to small sized bovine bone substitute (Bio-OssTM) results in an enhanced early implantation bed vascularization","volume":"4","author":"Barbeck","year":"2014","journal-title":"Ann. Maxillofac. Surg."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sieger, D., Korzinskas, T., Jung, O., Stojanovic, S., Wenisch, S., Smeets, R., Gosau, M., Schnettler, R., Najman, S., and Barbeck, M. (2019). The addition of high doses of hyaluronic acid to a biphasic bone substitute decreases the proinflammatory tissue response. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081969"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Flaig, I., Radenkovi\u0107, M., Najman, S., Pr\u00f6hl, A., Jung, O., and Barbeck, M. (2020). In vivo analysis of the biocompatibility and immune response of jellyfish collagen scaffolds and its suitability for bone regeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124518"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:09Z","timestamp":1760362389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":90,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073588"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073588","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]}}}