Owing to higher reproducibility and fine control over chemical composition and physical properties, various synthetic polymers have emerged as an attractive option for the formulation of hydrogels (Figure ). Polymers with ionizable groups that respond to pH changes and undergo protonation/deprotonation are of particular interest. Their conformation, configuration and solubility are modified according to the pH or ionic strength of the surrounding medium making them promising materials for sustained drug delivery. Among them, poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) are the most widely used. They both have good solubility in alkaline conditions due to ionization of carboxyl groups, but relatively low solubility under acidic conditions. This charge switch property has been exploited to formulate polyelectrolyte complex (PEC) hydrogels whose pHdependent stability has resulted in the sustained release of small molecules as well as proteins. Responsiveness to pH makes systems based on these polymers relevant for targeting the gastrointestinal tract, and they have been used in orally administered formulations to facilitate the delivery of drugs to the site of absorption. For instance, a poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) gel integrating pregabalin-loaded nanogels made of acryloyl group modified-cholesterol-bearing pullulan (CHPOA) prevented the release of the anticonvulsant drug at pH 2.2 due to chain collapse, but made it effective at pH 7.4, at which up to 90% of the drug was released in vitro from the swollen gel. Thermoresponsive polymers are another class of synthetic polymers employed in the formulation of hybrid hydrogels. They are characterized by a lower or upper critical solution temperature (LCST or UCST, respectively), which controls their aqueous solubility and triggers the sol-gel transition. N-isopropylacrylamide (NIPAAm)-based polymers are certainly the most widely used thermoresponsive polymers among them. The poly(Nisopropylacrylamide) (PNIPAAm) backbone contains both hydrophilic amide groups and hydrophobic isopropyl groups enabling the polymer to exhibit LCST behavior close to physiological conditions (around 32 °C). This feature has paved the way for diverse applications of these polymers in the biomedical field. Amphiphilic block copolymers consisting of polyester chains made of poly(lactic-coglycolic acid) (PLGA), PLA or poly(ε-caprolactone) (PCL) connected through a poly(ethylene glycol) (PEG) block, have also been extensively investigated thanks to their biodegradability and their LCST properties. These copolymers are water-soluble over a wide temperature range and can form micelles by self-assembly, with the hydrophobic polyester blocks confined to the core while hydrophilic PEG blocks form loops on the surface. As the temperature increases, hydrophobic interactions strengthen and bring the micelles close together, ultimately resulting in hydrogel formation. The sol-gel transition temperature can be controlled by adjusting the copolymer concentration and the nature of the polyester block. For instance, a PLGA-b-PEG-b-PLGA triblock copolymer solution at 30 wt% exhibits transition temperature close to 37 °C, leading to immediate gelation at body temperature. A similar value was measured for a PCLA-b-PEG-b-PCLA triblock copolymer solution at 20 wt% (where PCLA = poly(D,L-lactide-co-ε-caprolactone). Amphiphilic triblock copolymers composed of a central hydrophobic poly(propylene oxide) (PPO) block and two outer hydrophilic PEG blocks, known as poloxamers, also display thermosensitive behavior. Among them, poloxamer 407 (also termed Pluronic ® F-127), undergoes sol-gel transition at approximately 37 o C. Used concentrations are typically in the 20-30 wt% range leading to a rapid gelation well-suited for prolonged retention on wounds and in the intraperitoneal cavity. .