{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:31:32Z","timestamp":1791347492438,"version":"4.3.1"},"reference-count":58,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR project","doi-asserted-by":"publisher","award":["460734"],"award-info":[{"award-number":["460734"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7\u20133 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1\u03b2 expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials.<\/jats:p>","DOI":"10.3390\/jfb14020105","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T01:41:06Z","timestamp":1676338866000},"page":"105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Neovasculature in Axially Vascularized Calcium Phosphate Cement Scaffolds"],"prefix":"10.3390","volume":"14","author":[{"given":"Yassine","family":"Ouhaddi","sequence":"first","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Porge","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Montreal, QC H3A 1G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-0200","authenticated-orcid":false,"given":"Isadora","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Operative Dentistry, Department of General Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Gbureck","sequence":"additional","affiliation":[{"name":"Department of Functional Materials in Medicine and Dentistry, University of W\u00fcrzburg, D-97070 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Grover","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Gilardino","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-8920","authenticated-orcid":false,"given":"Edward","family":"Harvey","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Makhoul","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Montreal, QC H3A 1G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-6042","authenticated-orcid":false,"given":"Jake","family":"Barralet","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, QC H3G 1A4, Canada"},{"name":"Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Montreal, QC H3A 1G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2041731418776819","DOI":"10.1177\/2041731418776819","article-title":"Bone substitutes: A review of their characteristics, clinical use, and perspectives for large bone defects management","volume":"9","author":"Keller","year":"2018","journal-title":"J. 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