Injectable hyaluronic acid/PEG-p(HPMAm-lac)-based hydrogels dually cross-linked by thermal gelling and Michael addition

Abstract

Fast in situ forming thermosensitive hydrogels consisted of vinyl sulfone bearing p(HPMAm-lac1–2)-PEG-p(HPMAm-lac1–2) triblock copolymers and thiol modified hyaluronic acid were prepared via a dual cross-linking strategy based on thermal gelation at 37°C and simultaneous Michael addition cross-linking between vinyl sulfone and thiol moieties. The formation of a chemical network was varied within a time period of 9–60min by controlling the degree of vinyl sulfone derivatization, the triblock copolymer concentration and the degree of thiolation. The extent of thiol substitution on the polysaccharidic hyaluronan chain markedly affected the physical and mechanical properties, as well as the swelling and degradation behavior of the resulting networks, as confirmed by rheology, water uptake experiments and degradation tests. In addition, the developed hydrogels showed a good cytocompatibility in vitro during a timeframe of 21days both for mouse bone marrow stromal cell and for NIH 3T3 mouse fibroblasts. The developed hydrogels showed potential as promising injectable biomaterials with tunable gelation kinetics, adjustable mechanical properties, swelling and degradation times. These biomaterials could find application both as a regenerative cell matrix and as controlled drug delivery system.