Inflammatory response to dextrin-based hydrogel associated with human mesenchymal stem cells, urinary bladder matrix and Bonelike ® granules in rat subcutaneous implants

Increasing relevance has been attributed to hydrogels due to their ability to provide an extracellular matrix (ECM)-like environment for cellular adhesion and proliferation, acting as mechanical scaffolds for tissue remodeling or as delivery matrices. In vivo biocompatibility of a hybrid dextrin hydrogel produced from oxidized dextrin and adipic acid dihydrazide and its combinations with human mesenchymal stem cells (hMSCs), ECM from a porcine bladder (urinary bladder matrix) and ceramic granules (Bonelike ® ), was evaluated following ISO 10993 after subcutaneous implantation in a rat model. Histological analysis after 3 and 15 d showed typical acute and chronic inflammatory responses, respectively, with a more severe reaction exhibited whenever the ceramic granules were present. However, the dextrin hydrogel was able to stabilize granules in the implant site. Dextrin hydrogel was scored as slight irritant after 3 d, similar to its combination with UBM, and as non-irritant after 15 d. The presence of viable hMSCs in the subcutaneous tissue could be confirmed by the presence of anti-human nuclei antibody (HuNu + ) cells. The production of growth factors and inflammatory and immunomodulatory cytokines by these cells was also quantified in peripheral blood confirming the successful encapsulation of hMSCs into the hydrogel matrix for cell survival promotion. The presence of hMSCs seemed to modulate the inflammatory response by accelerating its progression when compared to the acellular experimental groups. Dextrin hydrogel has proven to be a biocompatible multifunctional matrix for minimally invasive biomedical procedures, including orthopedic surgeries when associated with bone substitutes and also as a possible encapsulation matrix for cell-based therapies.D M Silva was supported by the grant SFRH/BD/64571/2009 and A R Caseiro by the grant SFRH/BD/101174/2014 from Fundação para a Ciência e Tecnologia (FCT), Portugal. The authors thank the FCT Strategic project of UID/BIO/04469/2013, Pest-OE/AGR/UI0211/2011, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), and UID/EMS/00285/2013. This work was also funded by the project ‘BioHealth—Biotechnology and Bioengineering approaches to improve health quality’, ref. NORTE-07-0124-FEDER-000027, by the project ‘Dexgeleration—Soluções avançadas de regeneração óssea com base em hidrogéis de dextrino’, ref. Norte-07-0202-FEDER-038853, co-funded by the Programa Operacional Regional do Norte (ON.2—O Novo Norte), QREN, FEDER and the project ‘iBone Therapies: Terapias inovadoras para a regeneração óssea’, ref. NORTE-01-0247-FEDER-003262. IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT. This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the FCT, under project number PEst-C/SAU/LA0003/2013. The authors would like to thank IONISOS for performing gamma radiation sterilisation of oxidized dextrin solutions