In-situ Dually Cross-linked Hybrid Hyaluronan/p(HPMAm-lac)-PEG Hydrogels for Protein Release and Tissue Engineering

Hydrogels are cross-linked 3-dimensional polymeric networks displaying viscoelastic behavior and tissue-like mechanical properties1. Thermosensitive hydrogels are particularly promising materials as they are liquid, therefore injectable at room temperature and jellify in vivo, at body temperature, allowing minimally invasive administration2. In this work, a novel biodegradable and thermosensitive hydrogel as drug delivery and tissue engineering system was developed. Gelation kinetics, release behavior, cyto- and biocompatibility were studied in order to assess the applicability of such biomaterial for pharmaceutical and biomedical purposes. Hydrogels were tested for gelation kinetics by vial tilting method, mechanical properties by rheology (Physica – MCR 101 (Anton Paar) rheometer, 1Hz and 1% strain), degradation and release behavior by tests in phosphate buffer (PBS) pH 7.4 at 37°C. Hydrogel cytocompatibility with mouse bone marrow stromal cell (BMSCs) and NIH 3T3 mouse fibroblasts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Biocompatibility in vivo was assessed upon subcutaneous administration of placebo hydrogels in Balb/C mice. Rapidly gelling thermosensitive hydrogels with good cyto/biocompatibility and capability to controllably release active peptides were developed. This hydrogel technology holds great potential in the pharmaceutical and biomedical fields.