title: Inflammatory response to dextrin-based hydrogel associated with human mesenchymal stem cells, urinary bladder matrix and Bonelike®granules in rat subcutaneous implants.
abstract: 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.
authors: CEB-Centre of Biological Engineering, Universidade do Minho (UM), Campus de Gualtar, 4710-057 Braga, Portugal. Author to whom all correspondence should be addressed.
authors: Dina M
authors: DM
authors: Silva
authors: Ana Rita
authors: AR
authors: Caseiro
authors: Irina
authors: I
authors: Amorim
authors: Isabel
authors: I
authors: Pereira
authors: Fátima
authors: F
authors: Faria
authors: Tiago
authors: T
authors: Pereira
authors: José Domingos
authors: JD
authors: Santos
authors: Francisco Miguel
authors: FM
authors: Gama
authors: Ana Colette
authors: AC
authors: Maurício
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003912:Dextrins / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007249:Inflammation; D008297:Male; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D014018:Tissue Distribution; D023822:Tissue Engineering / Q000379:methods; D001743:Urinary Bladder / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D003912:Dextrins; D020100:Hydrogels; D010100:Oxygen