{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:24:23Z","timestamp":1791491063107,"version":"4.3.4"},"reference-count":277,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["180100008"],"award-info":[{"award-number":["180100008"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt Foundation","doi-asserted-by":"publisher","award":["Feodor Lynen Research Fellowship awarded to Markus Laubach"],"award-info":[{"award-number":["Feodor Lynen Research Fellowship awarded to Markus Laubach"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>The treatment of bone defects remains a challenging clinical problem with high reintervention rates, morbidity, and resulting significant healthcare costs. Surgical techniques are constantly evolving, but outcomes can be influenced by several parameters, including the patient\u2019s age, comorbidities, systemic disorders, the anatomical location of the defect, and the surgeon\u2019s preference and experience. The most used therapeutic modalities for the regeneration of long bone defects include distraction osteogenesis (bone transport), free vascularized fibular grafts, the Masquelet technique, allograft, and (arthroplasty with) mega-prostheses. Over the past 25 years, three-dimensional (3D) printing, a breakthrough layer-by-layer manufacturing technology that produces final parts directly from 3D model data, has taken off and transformed the treatment of bone defects by enabling personalized therapies with highly porous 3D-printed implants tailored to the patient. Therefore, to reduce the morbidities and complications associated with current treatment regimens, efforts have been made in translational research toward 3D-printed scaffolds to facilitate bone regeneration. Three-dimensional printed scaffolds should not only provide osteoconductive surfaces for cell attachment and subsequent bone formation but also provide physical support and containment of bone graft material during the regeneration process, enhancing bone ingrowth, while simultaneously, orthopaedic implants supply mechanical strength with rigid, stable external and\/or internal fixation. In this perspective review, we focus on elaborating on the history of bone defect treatment methods and assessing current treatment approaches as well as recent developments, including existing evidence on the advantages and disadvantages of 3D-printed scaffolds for bone defect regeneration. Furthermore, it is evident that the regulatory framework and organization and financing of evidence-based clinical trials remains very complex, and new challenges for non-biodegradable and biodegradable 3D-printed scaffolds for bone regeneration are emerging that have not yet been sufficiently addressed, such as guideline development for specific surgical indications, clinically feasible design concepts for needed multicentre international preclinical and clinical trials, the current medico-legal status, and reimbursement. These challenges underscore the need for intensive exchange and open and honest debate among leaders in the field. This goal can be addressed in a well-planned and focused stakeholder workshop on the topic of patient-specific 3D-printed scaffolds for long bone defect regeneration, as proposed in this perspective review.<\/jats:p>","DOI":"10.3390\/jfb14070341","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:45:11Z","timestamp":1687913111000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["The Concept of Scaffold-Guided Bone Regeneration for the Treatment of Long Bone Defects: Current Clinical Application and Future Perspective"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3451-1445","authenticated-orcid":false,"given":"Markus","family":"Laubach","sequence":"first","affiliation":[{"name":"Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia"},{"name":"Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia"},{"name":"Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistra\u00dfe 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-7762","authenticated-orcid":false,"given":"Sinduja","family":"Suresh","sequence":"additional","affiliation":[{"name":"Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia"},{"name":"Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wagels","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia"},{"name":"The Herston Biofabrication Institute, The University of Queensland, Herston, QLD 4006, Australia"},{"name":"Southside Clinical Division, School of Medicine, University of Queensland, Woolloongabba, QLD 4102, Australia"},{"name":"Department of Plastic and Reconstructive Surgery, Queensland Children\u2019s Hospital, South Brisbane, QLD 4101, Australia"},{"name":"The Australian Centre for Complex Integrated Surgical Solutions, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kobbe","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistra\u00dfe 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3402-2860","authenticated-orcid":false,"given":"Ulrich","family":"Kneser","sequence":"additional","affiliation":[{"name":"Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, 67071 Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris M.","family":"Holzapfel","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistra\u00dfe 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5678-2134","authenticated-orcid":false,"given":"Dietmar W.","family":"Hutmacher","sequence":"additional","affiliation":[{"name":"Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia"},{"name":"Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4059, Australia"},{"name":"Max Planck Queensland Centre (MPQC) for the Materials Science of Extracellular Matrices, Queensland University of Technology, Brisbane, QLD 4000, Australia"},{"name":"ARC Training Centre for Cell and Tissue Engineering Technologies (CTET), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4161\/org.23306","article-title":"Bone grafts, bone substitutes and orthobiologics: The bridge between basic science and clinical advancements in fracture healing","volume":"8","author":"Roberts","year":"2012","journal-title":"Organogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/nm1295-1322","article-title":"Bone tissue engineering","volume":"1","author":"Crane","year":"1995","journal-title":"Nat. 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