In vivo time-course biocompatibility assessment of biomagnetic nanoparticles-based biomaterials for tissue engineering applications
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Materials Science & Engineering C 118 (2021) 111476
Sponsorship• Grants FIS-PI17/0391 and FIS-PI17/0393 from Instituto de Salud Carlos III - ISCIII (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica I + D + i from the Spanish Ministerio de Ciencia e Innovación), co-financed by ERDF-FEDER, European Union. • Award number AC17/00013 (NanoGSkin) by ISCIII thorough AES 2017 and within the EuroNanoMed framework. • Grant FIS2017-85954-R funded by Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union. • Grants CS PI-0257-2017 and CSyF PE-0395-2019 from Consejería de Salud y Familias, Junta de Andalucía, Spain. • Grant n° Res SECYT 411/18 from SECYT (Secretary of Science and Technology of National University of Córdoba, Argentina) • Project Future Investments UCA JEDI, No. ANR-15-IDEX-01, project “RheoGel” by the French “Agence Nationale de la Recherche”.
Novel artificial tissues with potential usefulness in local-based therapies have been generated by tissue engineering using magnetic-responsive nanoparticles (MNPs). In this study, we performed a comprehensive in vivo characterization of bioengineered magnetic fibrin-agarose tissue-like biomaterials. First, in vitro analyses were performed and the cytocompatibility of MNPs was demonstrated. Then, bioartificial tissues were generated and subcutaneously implanted in Wistar rats and their biodistribution, biocompatibility and functionality were analysed at the morphological, histological, haematological and biochemical levels as compared to injected MNPs. Magnetic Resonance Image (MRI), histology and magnetometry confirmed the presence of MNPs restricted to the grafting area after 12 weeks. Histologically, we found a local initial inflammatory response that decreased with time. Structural, ultrastructural, haematological and biochemical analyses of vital organs showed absence of damage or failure. This study demonstrated that the novel magnetic tissue-like biomaterials with improved biomechanical properties fulfil the biosafety and biocompatibility requirements for future clinical use and support the use of these biomaterials as an alternative delivery route for magnetic nanoparticles.