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In this study, a validated design methodology is presented to evaluate AM as an effective fabrication technique for reconstruction of large bone defects after tumor resection in pediatric oncology patients. Implanting off-the-shelf components in pediatric patients is especially challenging because most standard components are sized and shaped for more common adult cases. While currently reported efforts on AM implants are focused on maxillofacial, hip and knee reconstructions, there have been no reported studies on reconstruction of proximal humerus tumors. A case study of a 9-year-old diagnosed with proximal humerus osteosarcoma was used to develop a patient-specific AM prosthesis for the humerus following tumor resection. Commonly used body-centered cubic (BCC) structures were incorporated at the surgical neck and distal interface in order to increase the effective surface area, promote osseointegration, and reduce the implant weight. A patient-specific prosthesis was fabricated using electron beam melting method from biocompatible Ti-6Al-4V. Both computational and biomechanical tests were performed on the prosthesis to evaluate its biomechanical behavior under varying loading conditions. Morphological analysis of the construct using micro-computed tomography was used to compare the as-designed and as-built prosthesis. It was found that the patient-specific prosthesis could withstand physiologically-relevant loading conditions with minimal permanent deformation (82<jats:italic>\u03bcm<\/jats:italic>after 10<jats:sup>5<\/jats:sup>cycles) at the medial aspect of the porous surgical neck. These outcomes support potential translation of the patient-specific AM prostheses to reconstruct large bone defects following tumor resection.<\/jats:p>","DOI":"10.1371\/journal.pone.0253786","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T17:29:51Z","timestamp":1626283791000},"page":"e0253786","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Additively manufactured patient-specific prosthesis for tumor reconstruction: Design, process, and properties"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-5813","authenticated-orcid":true,"given":"Maryam","family":"Tilton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory S.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Hast","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guha","family":"Manogharan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"pone.0253786.ref001","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-3-319-89542-0_2","volume-title":"Orthopedic Biomaterials: Progress in Biology, Manufacturing, and Industry Perspectives","author":"M Tilton","year":"2018"},{"key":"pone.0253786.ref002","volume-title":"Regenerative medicine applications in organ transplantation","author":"G Orlando","year":"2013"},{"key":"pone.0253786.ref003","article-title":"Revision of the loose glenoid component in anatomic total shoulder arthroplasty","author":"PH Flurin","year":"2013","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"pone.0253786.ref004","first-page":"166","volume-title":"Clinical Orthopaedics and Related Research","author":"BD Springer","year":"2009"},{"key":"pone.0253786.ref005","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.jse.2016.02.024","article-title":"Reverse total shoulder arthroplasty for acute head-splitting, 3- and 4-part fractures of the proximal humerus in the elderly","volume":"25","author":"F Grubhofer","year":"2016","journal-title":"J Shoulder Elb Surg"},{"key":"pone.0253786.ref006","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrendo.2017.101","article-title":"Is the osteosarcoma genome targetable?","volume":"13","author":"SA Savage","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"pone.0253786.ref007","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nrendo.2017.16","article-title":"Germline and somatic genetics of osteosarcoma\u2014connecting aetiology, biology and therapy","volume":"13","author":"DM Gianferante","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"pone.0253786.ref008","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s11999-014-3474-4","article-title":"Outcome after reconstruction of the proximal humerus for tumor resection: A systematic review","volume":"472","author":"T Teunis","year":"2014","journal-title":"Clin Orthop Relat Res"},{"key":"pone.0253786.ref009","article-title":"What is the Optimal Reconstruction Option after the Resection of Proximal Humeral Tumors? 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Taniguchi","year":"2016","journal-title":"Mater Sci Eng C"},{"key":"pone.0253786.ref022","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":"V Karageorgiou","year":"2005","journal-title":"Biomaterials"},{"key":"pone.0253786.ref023","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jbm.820170105","article-title":"Fatigue properties of implant materials in hip prosthesis form: A standardized test","volume":"17","author":"P Ducheyne","year":"1983","journal-title":"J Biomed Mater Res"},{"key":"pone.0253786.ref024","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.jbiomech.2009.05.035","article-title":"In vivo measurement of shoulder joint loads during activities of daily living","volume":"42","author":"P Westerhoff","year":"2009","journal-title":"J 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biomed eng"},{"key":"pone.0253786.ref028","first-page":"2","article-title":"Calcar screw position in proximal humerus fracture fixation: Don\u2019t miss high!","author":"S Mehta","year":"2018","journal-title":"Injury"},{"key":"pone.0253786.ref029","first-page":"1","article-title":"Biomechanical analysis of plate systems for proximal humerus fractures: a systematic literature review","author":"A Jabran","year":"2018","journal-title":"Biomed Eng Online"},{"key":"pone.0253786.ref030","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.clinbiomech.2014.06.008","article-title":"Biomechanical effects of calcar screws and bone block augmentation on medial support in locked plating of proximal humeral fractures","volume":"29","author":"JC Katthagen","year":"2014","journal-title":"Clin Biomech"},{"key":"pone.0253786.ref031","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1097\/TA.0b013e3181beed96","article-title":"The biomechanics of locked plating for repairing proximal humerus fractures with or without medial cortical support","volume":"69","author":"J Lescheid","year":"2010","journal-title":"J Trauma\u2014Inj Infect Crit Care"},{"key":"pone.0253786.ref032","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.medengphy.2018.04.011","article-title":"Validated computational framework for efficient systematic evaluation of osteoporotic fracture fixation in the proximal humerus","volume":"57","author":"P Varga","year":"2018","journal-title":"Med Eng Phys"},{"key":"pone.0253786.ref033","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1016\/j.jbiomech.2006.10.037","article-title":"In vivo glenohumeral contact forces-Measurements in the first patient 7 months postoperatively","volume":"40","author":"G Bergmann","year":"2007","journal-title":"J Biomech"},{"key":"pone.0253786.ref034","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1093\/bioinformatics\/btx180","article-title":"Trainable Weka Segmentation: A machine learning tool for microscopy pixel classification","volume":"33","author":"I Arganda-Carreras","year":"2017","journal-title":"Bioinformatics"},{"key":"pone.0253786.ref035","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of Image Analysis","volume":"9","author":"CA Schneider","year":"2017","journal-title":"Nat Methods"},{"key":"pone.0253786.ref036","first-page":"10","volume-title":"The WEKA Data Mining Software: An Update","author":"M Hall"},{"key":"pone.0253786.ref037","doi-asserted-by":"crossref","first-page":"6553","DOI":"10.1088\/0031-9155\/61\/17\/6553","article-title":"Tissue segmentation of computed tomography images using a Random Forest algorithm: A feasibility study","volume":"61","author":"DF Polan","year":"2016","journal-title":"Phys Med Biol"},{"key":"pone.0253786.ref038","unstructured":"Vaupel M. Optical Analysis of Shape and Roughness of a Gear Wheel. Carl Zeiss Microsc GmbH."},{"key":"pone.0253786.ref039","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jmbbm.2017.07.004","article-title":"Fatigue failure of plated osteoporotic proximal humerus fractures is predicted by the strain around the proximal screws","volume":"75","author":"P Varga","year":"2017","journal-title":"J Mech Behav Biomed Mater"},{"key":"pone.0253786.ref040","first-page":"1","article-title":"Screw configuration in proximal humerus plating has a significant impact on fixation failure risk predicted by finite element models","author":"JWA Fletcher","year":"2019","journal-title":"J Shoulder Elb Surg"},{"key":"pone.0253786.ref041","first-page":"329","volume":"7","author":"K Kieswetter","year":"1996","journal-title":"THE ROLE OF IMPLANT SURFACE CHARACTERISTICS"},{"key":"pone.0253786.ref042","first-page":"104","volume":"53","author":"M Meischel","year":"2016","journal-title":"Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications"},{"key":"pone.0253786.ref043","author":"SC Cox","year":"2017","journal-title":"Surface Finish has a Critical In fl uence on Bio fi lm Formation and Mammalian Cell Attachment to Additively Manufactured Prosthetics"},{"key":"pone.0253786.ref044","doi-asserted-by":"crossref","first-page":"e00054","DOI":"10.1016\/j.bprint.2019.e00054","article-title":"Bioprinting Additive manufacturing process creates local surface roughness modi fi cations leading to variation in cell adhesion on multifaceted","volume":"16","author":"A Lerebours","year":"2019","journal-title":"Bioprinting"},{"key":"pone.0253786.ref045","first-page":"1","article-title":"An Overview of Materials with Triply Periodic Minimal Surfaces and Related Geometry: From Biological Structures to Self-Assembled Systems","volume":"30","author":"L Han","year":"2018","journal-title":"Adv Mater"},{"key":"pone.0253786.ref046","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1016\/j.actbio.2012.10.020","article-title":"Modelling the role of surface stress on the kinetics of tissue growth in confined geometries","volume":"9","author":"E Gamsj\u00e4ger","year":"2013","journal-title":"Acta Biomater"},{"key":"pone.0253786.ref047","first-page":"119739","volume-title":"Biomaterials","author":"SJP Callens","year":"2020"},{"key":"pone.0253786.ref048","first-page":"1","author":"SJP Callens","year":"2020","journal-title":"Emergent collective organization of bone cells in complex curvature fields"},{"key":"pone.0253786.ref049","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jmbbm.2015.06.024","article-title":"Ti\u20136Al\u20134V triply periodic minimal surface structures for bone implants fabricated via selective laser melting","volume":"51","author":"C Yan","year":"2015","journal-title":"J Mech Behav Biomed 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