Recent advances in glucose-responsive insulin delivery systems: novel hydrogels and future applications

Abstract

Over the past several decades, there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus. The introduction of closed loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this field. These systems consist of encapsulated glucose-sensitive components such as glucose oxidase (GOx) or phenylboronic acid (PBA) in hydrogels, microgels, or nanoparticles. Since our previous evaluation of these systems in a contribution in 2004, new systems have been developed. Important improvements in key issues, such as consistent insulin delivery over an extended period of time have been addressed. In this contribution, we discuss recent advancements over the last five years and present persisting issues in these technologies that must be overcome in order for these systems to be applicable in patients.

Recent advances in responsive hydrogels for diabetic wound healing

“…Recently, smart hydrogels with stimulus-responsive functions have attracted considerable attention. Briefly, stimulus-responsive hydrogels can respond to internal physiological signals (i.e., temperature [ 28 , 29 ], pH [ 30 , 31 ], redox [ 32 , 33 ], glucose [ 34 , 35 ], or enzymes [ 36 , 37 ]), external stimuli (i.e., temperature [ 38 , 39 ], magnetic field [ 40 , 41 ], pressure [ 42 , 43 ], reactive oxygen species (ROS) [ 44 , 45 ], light [ 46 , 47 ] and electric field [ 48 , 49 ]) or a combination of the above, which can reversibly or irreversibly change the physical properties or chemical structure ( Fig. 2 ).…”

Stimuli-responsive peptide hydrogels for biomedical applications

“…7a). 96 Aside from these bioactive molecules, common endogenous compounds like reactive oxygen species 97,98 and glucose 99 can also act as stimuli, inducing analogous responses in peptide hydrogels (Fig. 7b).…”

“…In addition to the examples above, stimuli-responsive peptide hydrogels can serve as hormone delivery systems to effectively regulate physiological processes and maintain body homeostasis. 99,129 For instance, Fu et al developed a glucoseresponsive insulin delivery system comprising non-covalently crosslinked pH-responsive peptide hydrogels, encapsulated insulin, and enzymes. 39 Within this system, glucose undergoes catalytic conversion to gluconic acid, leading to localized acidification.…”

Wound microenvironment self-adaptive all-in-one hydrogel for rapid healing of the diabetic wound

“…13 This impressive progress in utilizing glucose-responsive hydrogels significantly enhanced the field of diabetic wound repair. 14,15 Nonetheless, most of the existing smart hydrogels remain single-function entities with inadequate adaptability to the wound microenvironment and do not adequately align with the intricate healing mechanisms governing diabetic wounds. The process of diabetic wound healing is multifaceted and influenced by an array of factors.…”