{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:11:09Z","timestamp":1789031469303,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nobel Biocare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Three-dimensionally (3D)-printed alpha-tricalcium phosphate (\u03b1-TCP) scaffolds, fabricated through a low-temperature hydrothermal dissolution-precipitation process, replicate the structural and compositional features of native bone. Reinforcing hydrothermally processed \u03b1-TCP with poly(lactic-co-glycolic acid) (PLGA) as a binder has previously been shown to confer distinct mechanical advantages, supporting its potential as a viable material for bone regenerative scaffolds. Although the hydrothermal processing of \u03b1-TCP scaffolds and PLGA-based mechanical reinforcement have each been characterized individually in earlier studies, this work represents the first pre-clinical in vivo assessment of osseoconduction and biocompatibility of 3D-printed, PLGA-reinforced, self-hardening calcium phosphate scaffolds in a large translational animal model. A ceramic ink suitable for extrusion was prepared by combining a 30 wt\/vol% poloxamer 407 solution with \u03b1-TCP powder at a 0.45 wt\/wt ratio (CTRL). A second extrudable ink, consisting of an \u03b1-TCP ceramic suspension incorporating a 35 wt\/wt% PLGA binder, was formulated at a 0.5 wt\/wt ratio (EXP). Cylindrical scaffolds (6 mm \u00d7 6 mm) were fabricated at room temperature using a custom-built Direct Ink Write 3D printer, then hydrothermally treated via submersion in water and thermal consolidation at 121 \u00b0C. Osteotomies were created in the ilium of adult sheep, with two cylindrical defects (7 mm \u00d7 6 mm) per animal, each receiving either a CTRL or EXP scaffold. Animals were euthanized at 3 and 12 weeks post-surgery (n = 6 animals per time point), and samples were collected en bloc for analysis. For both scaffold formulations, hard tissue formed by 12 weeks displayed high cellularity and active vascularization, consistent with early woven bone formation. Quantitative analysis revealed no significant between-group differences in bone formation at either time point (p &gt; 0.05). These findings indicate that 3D-printed, PLGA-reinforced, self-hardening \u03b1-TCP scaffolds are osseoconductive and biocompatible, supporting their potential use in orthopedic and craniomaxillofacial bone defect repair.<\/jats:p>","DOI":"10.3390\/bioengineering13091049","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:01:56Z","timestamp":1788966116000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3D-Printed Poly(Lactic-co-Glycolic Acid) Binder-Based Self-Hardening Calcium Phosphate Bone Scaffolds"],"prefix":"10.3390","volume":"13","author":[{"given":"Savanah R.","family":"Sturm","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0941-6605","authenticated-orcid":false,"given":"Nicholas A.","family":"Mirsky","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7012-0920","authenticated-orcid":false,"given":"Adriana I.","family":"Sandino","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Maria","family":"Castellon","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Anshumi J.","family":"Desai","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Isabella D.","family":"Guanche","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Linh","family":"Johansson","sequence":"additional","affiliation":[{"name":"Mimetis Biomaterials S.L., Carrer de Cartagena, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8302-3002","authenticated-orcid":false,"given":"Yago","family":"Raymond","sequence":"additional","affiliation":[{"name":"Mimetis Biomaterials S.L., Carrer de Cartagena, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Vasudev Vivekanand","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-6527","authenticated-orcid":false,"given":"Lukasz","family":"Witek","sequence":"additional","affiliation":[{"name":"Biomaterials and Regenerative Biology Division, NYU College of Dentistry, New York, NY 10010, USA"},{"name":"Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY 11201, USA"},{"name":"Hansj\u00f6rg Wyss Department of Plastic Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA"},{"name":"Department of Oral and Maxillofacial Surgery, NYU College of Dentistry, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Paulo G.","family":"Coelho","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41368-024-00327-7","article-title":"Personalized bioceramic grafts for craniomaxillofacial bone regeneration","volume":"16","author":"Rahimnejad","year":"2024","journal-title":"Int. J. Oral Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.acra.2019.08.011","article-title":"Medical 3D printing cost-savings in orthopedic and maxillofacial surgery: Cost analysis of operating room time saved with 3D printed anatomic models and surgical guides","volume":"27","author":"Ballard","year":"2020","journal-title":"Acad. Radiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.glohj.2022.11.001","article-title":"3D printing applications for healthcare research and development","volume":"6","author":"Javaid","year":"2022","journal-title":"Glob. Health J."},{"key":"ref_4","first-page":"94","article-title":"Robocasting provides MOULDLESS fabrication from slurry deposition","volume":"148","author":"Cesarano","year":"1998","journal-title":"Ceram. Ind."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103095","DOI":"10.1016\/j.cis.2024.103095","article-title":"Innovations in hydrogel-based manufacturing: A comprehensive review of direct ink writing technique for biomedical applications","volume":"324","author":"Baniasadi","year":"2024","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ielo, I., Calabrese, G., De Luca, G., and Conoci, S. (2022). Recent advances in hydroxyapatite-based biocomposites for bone tissue regeneration in orthopedics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179721"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Eliaz, N., and Metoki, N. (2017). Calcium phosphate bioceramics: A review of their history, structure, properties, coating technologies and biomedical applications. Materials, 10.","DOI":"10.3390\/ma10040334"},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.21873\/invivo.11875","article-title":"Hydroxyapatite nanoparticles as injectable bone substitute material in a vertical bone augmentation model","volume":"34","author":"Kaneko","year":"2020","journal-title":"In Vivo"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.msec.2018.12.059","article-title":"Antibacterial bone substitute of hydroxyapatite and magnesium oxide to prevent dental and orthopaedic infections","volume":"97","author":"Coelho","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1097\/SAP.0000000000002965","article-title":"Transforming the degradation rate of \u03b2-tricalcium phosphate bone replacement using 3-dimensional printing","volume":"87","author":"Shen","year":"2021","journal-title":"Ann. Plast. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.msec.2015.11.040","article-title":"Preparation, characterization and in vitro dissolution behavior of porous biphasic \u03b1\/\u03b2-tricalcium phosphate bioceramics","volume":"59","author":"Xie","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109288","DOI":"10.1016\/j.identj.2025.109288","article-title":"Harnessing and Optimizing \u03b1-TCP for Oral Tissue Engineering and Regenerative Dentistry","volume":"76","author":"Du","year":"2026","journal-title":"Int. Dent. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"213098","DOI":"10.1016\/j.bioadv.2022.213098","article-title":"A new injectable quick hardening anti-collapse bone cement allows for improving biodegradation and bone repair","volume":"141","author":"Chen","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.actbio.2021.09.001","article-title":"Hydrothermal processing of 3D-printed calcium phosphate scaffolds enhances bone formation in vivo: A comparison with biomimetic treatment","volume":"135","author":"Raymond","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100566","DOI":"10.1016\/j.oceram.2024.100566","article-title":"Densification of hydroxyapatite through cold sintering process: Role of liquid phase chemistry and physical characteristic of HA powder","volume":"17","author":"Kumar","year":"2024","journal-title":"Open Ceram."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.actbio.2008.07.018","article-title":"Biocompatibility and osteogenicity of degradable Ca-deficient hydroxyapatite scaffolds from calcium phosphate cement for bone tissue engineering","volume":"5","author":"Guo","year":"2009","journal-title":"Acta Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1023\/A:1011280828663","article-title":"Surface reaction of stoichiometric and calcium-deficient hydroxyapatite in simulated body fluid","volume":"12","author":"Lin","year":"2001","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s10853-007-1853-x","article-title":"Hydrothermal processing of materials: Past, present and future","volume":"43","author":"Yoshimura","year":"2008","journal-title":"J. Mater. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.actbio.2024.02.012","article-title":"Toughening 3D printed biomimetic hydroxyapatite scaffolds: Polycaprolactone-based self-hardening inks","volume":"177","author":"Johansson","year":"2024","journal-title":"Acta Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127635","DOI":"10.1016\/j.polymer.2024.127635","article-title":"Direct ink writing of customized polymeric structures embedded in a nano-silicate based supporting matrix","volume":"312","author":"Mohol","year":"2024","journal-title":"Polymer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.progpolymsci.2019.05.004","article-title":"Degradation mechanisms of polycaprolactone in the context of chemistry, geometry and environment","volume":"96","author":"Bartnikowski","year":"2019","journal-title":"Prog. Polym. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ilyas, R., Zuhri, M., Norrrahim, M.N.F., Misenan, M.S.M., Jenol, M.A., Samsudin, S.A., Nurazzi, N., Asyraf, M., Supian, A., and Bangar, S.P. (2022). Natural fiber-reinforced polycaprolactone green and hybrid biocomposites for various advanced applications. Polymers, 14.","DOI":"10.3390\/polym14010182"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"46300","DOI":"10.1016\/j.ceramint.2024.08.473","article-title":"Enhancing the mechanical performance of 3D-printed self-hardening calcium phosphate bone scaffolds: PLGA-based strategies","volume":"50","author":"Johansson","year":"2024","journal-title":"Ceram. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"024101","DOI":"10.1088\/1758-5090\/aa6370","article-title":"3D printing PLGA: A quantitative examination of the effects of polymer composition and printing parameters on print resolution","volume":"9","author":"Guo","year":"2017","journal-title":"Biofabrication"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fu, C., Bai, H., Zhu, J., Niu, Z., Wang, Y., Li, J., Yang, X., and Bai, Y. (2017). Enhanced cell proliferation and osteogenic differentiation in electrospun PLGA\/hydroxyapatite nanofibre scaffolds incorporated with graphene oxide. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188352"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5892506","DOI":"10.1155\/2020\/5892506","article-title":"Enhanced Cell Proliferation and Osteogenesis Differentiation through a Combined Treatment of Poly-L-Lysine-Coated PLGA\/Graphene Oxide Hybrid Fiber Matrices and Electrical Stimulation","volume":"2020","author":"Zhu","year":"2020","journal-title":"J. Nanomater."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Johansson, L., Latorre, J.L., Liversain, M., Thorel, E., Raymond, Y., and Ginebra, M.-P. (2024). Three-Dimensional Printed Patient-Specific Vestibular Augmentation: A Case Report. J. Clin. Med., 13.","DOI":"10.3390\/jcm13082408"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112064","DOI":"10.1016\/j.matdes.2023.112064","article-title":"Ceramic materials for 3D printing of biomimetic bone scaffolds\u2014Current state-of-the-art & future perspectives","volume":"231","author":"Budharaju","year":"2023","journal-title":"Mater. Des."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Netti, P.A., Biondi, M., and Frigione, M. (2020). Experimental studies and modeling of the degradation process of poly(lactic-co-glycolic acid) microspheres for sustained protein release. Polymers, 12.","DOI":"10.3390\/polym12092042"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biomaterials.2015.07.026","article-title":"Textured and hierarchically structured calcium phosphate ceramic blocks through hydrothermal treatment","volume":"67","author":"Galea","year":"2015","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41722","DOI":"10.1021\/acsami.7b14175","article-title":"Osteoinduction by foamed and 3D-printed calcium phosphate scaffolds: Effect of nanostructure and pore architecture","volume":"9","author":"Barba","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.11607\/prd.3504","article-title":"Absence of Healing Impairment in Osteotomies Prepared via Osseodensification Drilling","volume":"39","author":"Witek","year":"2019","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114992","DOI":"10.1016\/j.mtcomm.2026.114992","article-title":"A hybrid CFD\u2013Machine Learning framework for efficient permeability prediction in 3D-printed bone scaffold design","volume":"52","author":"Amirpour","year":"2026","journal-title":"Mater. Today Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1007\/s00170-025-15079-9","article-title":"Hybrid 3D printing of fluid-filled lattices for biomedical applications: A review","volume":"136","author":"Amirpour","year":"2025","journal-title":"Int. J. Adv. Manuf. Technol."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/9\/1049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:53:20Z","timestamp":1789030400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/9\/1049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["bioengineering13091049"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13091049","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}