{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:13:02Z","timestamp":1778548382373,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003417","name":"Deutsche Gesetzliche Unfallversicherung","doi-asserted-by":"publisher","award":["FR252"],"award-info":[{"award-number":["FR252"]}],"id":[{"id":"10.13039\/501100003417","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague\u2013Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by \u00b5-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.<\/jats:p>","DOI":"10.3390\/cells10082058","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T08:35:52Z","timestamp":1628670952000},"page":"2058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-478X","authenticated-orcid":false,"given":"Holger","family":"Freischmidt","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, BG Trauma Center Ludwigshafen at Heidelberg University Hospital, 67071 Ludwigshafen am Rhein, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Armbruster","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, BG Trauma Center Ludwigshafen at Heidelberg University Hospital, 67071 Ludwigshafen am Rhein, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Bonner","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, BG Trauma Center Ludwigshafen at Heidelberg University Hospital, 67071 Ludwigshafen am Rhein, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Guehring","sequence":"additional","affiliation":[{"name":"Trauma Centre, Hospital Paulinenhilfe Stuttgart at T\u00fcbingen University Hospital, Rosenbergstr. 38, 70176 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-5939","authenticated-orcid":false,"given":"Dennis","family":"Nurjadi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Medical Microbiology and Hygiene, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-5438","authenticated-orcid":false,"given":"Maren","family":"Bechberger","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Heidelberg University Hospital, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-7528","authenticated-orcid":false,"given":"Robert","family":"Sonntag","sequence":"additional","affiliation":[{"name":"Laboratory of Biomechanics and Implant Research, Clinic for Orthopedics and Trauma Surgery, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Schmidmaier","sequence":"additional","affiliation":[{"name":"Clinic for Orthopedics and Trauma Surgery, Center for Orthopedics, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-4782","authenticated-orcid":false,"given":"Paul Alfred","family":"Gr\u00fctzner","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, BG Trauma Center Ludwigshafen at Heidelberg University Hospital, 67071 Ludwigshafen am Rhein, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Helbig","sequence":"additional","affiliation":[{"name":"Clinic for Orthopedics and Trauma Surgery, Center for Orthopedics, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1080\/17453674.2017.1321351","article-title":"The risk of non-union per fracture: Current myths and revised figures from a population of over 4 million adults","volume":"88","author":"Mills","year":"2017","journal-title":"Acta Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00003086-199810001-00003","article-title":"The cell and molecular biology of fracture healing","volume":"355","author":"Einhorn","year":"1998","journal-title":"Clin. 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PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226163"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/2058\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:13Z","timestamp":1760165053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/2058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cells10082058"],"URL":"https:\/\/doi.org\/10.3390\/cells10082058","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]}}}