{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:58:20Z","timestamp":1790827100378,"version":"4.1.0"},"reference-count":157,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publishing Fund of the University of T\u00fcbingen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2\u201310% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.<\/jats:p>","DOI":"10.3390\/bioengineering10010085","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T07:05:09Z","timestamp":1673247909000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions\u2014Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-3710","authenticated-orcid":false,"given":"Dominik","family":"Saul","sequence":"first","affiliation":[{"name":"Department of Trauma and Reconstructive Surgery, Eberhard Karls University T\u00fcbingen, BG Trauma Center T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Kogod Center on Aging and Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1261-9877","authenticated-orcid":false,"given":"Maximilian M.","family":"Menger","sequence":"additional","affiliation":[{"name":"Department of Trauma and Reconstructive Surgery, Eberhard Karls University T\u00fcbingen, BG Trauma Center T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Ehnert","sequence":"additional","affiliation":[{"name":"Department of Trauma and Reconstructive Surgery, Eberhard Karls University T\u00fcbingen, BG Trauma Center T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-6791","authenticated-orcid":false,"given":"Andreas K.","family":"N\u00fcssler","sequence":"additional","affiliation":[{"name":"Department of Trauma and Reconstructive Surgery, Eberhard Karls University T\u00fcbingen, BG Trauma Center T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Histing","sequence":"additional","affiliation":[{"name":"Department of Trauma and Reconstructive Surgery, Eberhard Karls University T\u00fcbingen, BG Trauma Center T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-8456","authenticated-orcid":false,"given":"Matthias W.","family":"Laschke","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100740","DOI":"10.1016\/j.bonr.2020.100740","article-title":"The investigation of bone fracture healing under intramembranous and endochondral ossification","volume":"14","author":"Ghimire","year":"2021","journal-title":"Bone Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102668","DOI":"10.1016\/j.jhevol.2019.102668","article-title":"Early Upper Paleolithic human foot bones from Manot Cave, Israel","volume":"160","author":"Borgel","year":"2021","journal-title":"J. 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