Temperature-Responsive Hydrogels: Materials, Mechanisms and Biological Applications

During the last decades, an increasing attention has been paid to pharmaceutical and biomedical applications of queous polymeric solutions which respond in accordance to the changes in their environmental conditions i.e., stimuli by turning into in situ forming hydrogels. Of all the stimuli-responsive hydrogels, temperature-responsive solutions have been widely investigated due to their simplicity, applicability and relatively high frequency of temperature-responsiveness, in situ gelling polymeric (natural or synthetic) systems. In contrast with the conventional hydrogels, in situ forming temperature-responsive hydrogels can form under physiological conditions and preserve their morphological integrity for a definite time course. Using the materials makes it easier to formulate pharmaceutical formulations by mixing polymer and drug, and also improve the dissolution of hydrophobic drugs with low molecular weight. Due to the simplicity of the pharmaceutical formulation by simple solution mixing, biocompatibility and convenient usage these materials can be used in biomedical and pharmaceutical fields for tissue engineering, solubilizing of sparingly soluble drug molecules, controlled delivery of drugs and biomacromolecules, such as proteins and genes. In this review, temperature-responsive hydrogels are studied regarding their classification, applications and thermodynamics. Moreover, temperature-responsiveness mechanisms, polymeric gels, recent advances in surface, hydrogel and molecular design and biomedical application are investigated. Also, this review focuses on recent investigation based on the designs of temperature-responsive micelles and intelligent bioconjugates. Finally, limitations and potentials of applications of the temperature-responsive in situ forming hydrogels have been reported. The reported information in this paper are necessary to design and develop a desirable temperature-responsive hydrogels with different characteristics and applications.