Smart hydrogels and the promise of multi-responsive in-situ systems

Gels have gained significant prominence in pharmaceutical sciences due to their advantageous properties for drug delivery applications. Among the various gel types, hydrogels are particularly noteworthy for their extensive utilization in this domain. Recent advancements in in-situ hydrogels highlight their customizable properties, biomimetic designs, and responsive features, which enhance their applications in drug delivery, tissue engineering, and regenerative medicine. Innovations such as 3D bioprinting integration and the use of natural polymers have further underscored the clinical relevance and translational potential of these versatile biomaterials. This review discusses intelligent hydrogels and their unique ability to transition between gel and sol states in response to specific stimuli, enabling sustained drug release while retaining their gel form until triggered. These smart hydrogels can be categorized into systems responsive to physiological stimuli and those responsive to chemical stimuli. The review also discusses the development of dual-, triple-, and multi-responsive hydrogels which have emerged as a response to the limitations of mono-responsive systems thus offering enhanced versatility in drug delivery. Although several mono-responsive in-situ gels have entered the market in recent years, there is a growing demand for the commercialization of multi-responsive in-situ gels, which promise improved therapeutic outcomes through their adaptive release mechanisms. This review discusses these challenges and the benefits associated with potential commercialization.