{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T10:16:00Z","timestamp":1777284960659,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"North Portugal Regional Operational Programme (NORTE 2020)","award":["NORTE-01-0247-FEDER-023345"],"award-info":[{"award-number":["NORTE-01-0247-FEDER-023345"]}]},{"name":"Programa Operacional Factores de Competitividade (COMPETE)","award":["POCI\/01\/0145\/FEDER\/007265"],"award-info":[{"award-number":["POCI\/01\/0145\/FEDER\/007265"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Designing biomaterials for bone-substitute applications is still a challenge regarding the natural complex structure of hard tissues. Aiming at bone regeneration applications, scaffolds based on natural collagen and synthetic nanohydroxyapatite were developed, and they showed adequate mechanical and biological properties. The objective of this work was to perform and evaluate a scaled-up production process of this porous biocomposite scaffold, which promotes bone regeneration and works as a barrier for both fibrosis and the proliferation of scar tissue. The material was produced using a prototype bioreactor at an industrial scale, instead of laboratory production at the bench, in order to produce an appropriate medical device for the orthopedic market. Prototypes were produced in porous membranes that were e-beam irradiated (the sterilization process) and then analysed by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), dynamic mechanical analysis (DMA), cytotoxicity tests with mice fibroblasts (L929), human osteoblast-like cells (MG63) and human MSC osteogenic differentiation (HBMSC) with alkaline phosphatase (ALP) activity and qPCR for osteogenic gene expression. The prototypes were also implanted into critical-size bone defects (rabbits\u2019 tibia) for 5 and 15 weeks, and after that were analysed by microCT and histology. The tests performed for the physical characterization of the materials showed the ability of the scaffolds to absorb and retain water-based solvents, as well as adequate mechanical resistance and viscoelastic properties. The cryogels had a heteroporous morphology with microporosity and macroporosity, which are essential conditions for the interaction between the cells and materials, and which consequently promote bone regeneration. Regarding the biological studies, all of the studied cryogels were non-cytotoxic by direct or indirect contact with cells. In fact, the scaffolds promoted the proliferation of the human MSCs, as well as the expression of the osteoblastic phenotype (osteogenic differentiation). The in vivo results showed bone tissue ingrowth and the materials\u2019 degradation, filling the critical bone defect after 15 weeks. Before and after irradiation, the studied scaffolds showed similar properties when compared to the results published in the literature. In conclusion, the material production process upscaling was optimized and the obtained prototypes showed reproducible properties relative to the bench development, and should be able to be commercialized. Therefore, it was a successful effort to harness knowledge from the basic sciences to produce a new biomedical device and enhance human health and wellbeing.<\/jats:p>","DOI":"10.3390\/ma14154130","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:06:21Z","timestamp":1627250781000},"page":"4130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Translational Research for Orthopedic Bone Graft Development"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-7711","authenticated-orcid":false,"given":"Maria J. C.","family":"Vilela","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Nacional de Engenharia Biom\u00e9dica (INEB), 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Bruno J. A.","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Animal Science, CECAV\u2014Animal and Veterinary Research Centre UTAD, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-8030","authenticated-orcid":false,"given":"Jos\u00e9","family":"Ventura","sequence":"additional","affiliation":[{"name":"Artur Salgado S.A., 4250-288 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4605","authenticated-orcid":false,"given":"Fernando J. M.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Nacional de Engenharia Biom\u00e9dica (INEB), 4200-135 Porto, Portugal"},{"name":"Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal"}]},{"given":"Christiane L.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Nacional de Engenharia Biom\u00e9dica (INEB), 4200-135 Porto, Portugal"},{"name":"Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0962-8924(98)01362-2","article-title":"ECM signalling: Orchestrating cell behaviour and misbehaviour","volume":"8","author":"Lukashev","year":"1998","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1002\/1521-3773(20020902)41:17<3130::AID-ANIE3130>3.0.CO;2-1","article-title":"Biological and medical significance of calcium phosphates","volume":"41","author":"Dorozhkin","year":"2002","journal-title":"Angew. 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