title: In vivo biocompatibility of p(HPMAm-lac)-PEG hydrogels hybridized with hyaluronan.
abstract: The present study reports on the biocompatibility in vivo after intramuscular and subcutaneous administration in Balb/c mice of vinyl sulphone bearing p(HPMAm-lac1-2)-PEG-p(HPMAm-lac1-2)/thiolated hyaluronic acid hydrogels, designed as novel injectable biomaterials for potential application in the fields of tissue engineering and regenerative medicine. Ultrasonography, used as a method to study hydrogel gelation and residence time in vivo, showed that, upon injection, the biomaterial efficiently formed a hydrogel by simultaneous thermal gelation and Michael Addition cross-linking forming a viscoelastic spherical depot at the injection site. The residence time in vivo (20 days) was found to be shorter than that observed in vitro (32 days), indicating that the injected hydrogel was resorbed not only by chemical hydrolysis but also by cellular metabolism and/or enzymatic activity. Systemic biocompatibility was tested by analysing routine haematological parameters at different time-points (7, 14 and 21 days after administration) and histology of the main organs, including the haematopoietic system. No statistically significant difference between parameters of the saline-treated group and those of the hydrogel-treated group was found. Importantly, a time-dependent decrease of important pro-inflammatory cytokines (TREM1 (Triggering Receptor Expressed on Myeloid cells-1), tumour necrosis factor-α and interleukin-1β) in cultured bone marrow cells extracted from hydrogel treated mice was observed, possibly correlated to the anti-inflammatory effect of hyaluronic acid released in time as hydrogel degraded. Copyright © 2016 John Wiley & Sons, Ltd.
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
authors: Maria Giovanna
authors: MG
authors: Sabbieti
authors: School of Pharmacy, University of Camerino, Camerino, (MC), Italy.
authors: Alessandra
authors: A
authors: Dubbini
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, (MC), Italy.
authors: Fulvio
authors: F
authors: Laus
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, (MC), Italy.
authors: Emanuele
authors: E
authors: Paggi
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, (MC), Italy.
authors: Andrea
authors: A
authors: Marchegiani
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
authors: Melania
authors: M
authors: Capitani
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
authors: Luigi
authors: L
authors: Marchetti
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, (MC), Italy.
authors: Fabrizio
authors: F
authors: Dini
authors: Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands.
authors: Tina
authors: T
authors: Vermonden
authors: School of Pharmacy, University of Camerino, Camerino, (MC), Italy.
authors: Piera
authors: P
authors: Di Martino
authors: School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, (MC), Italy.
authors: Dimitrios
authors: D
authors: Agas
authors: School of Pharmacy, University of Camerino, Camerino, (MC), Italy.
authors: Roberta
authors: R
authors: Censi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016207:Cytokines; D020100:Hydrogels; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid
keywords: biodegradation; echosonographic analysis; histology; in vivo biocompatibility; inflammatory cytokines; injectable thermosensitive hydrogels