Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Abstract

Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

Natural Polymeric Hydrogels Encapsulating Small Molecules for Diabetic Wound Healing

“…Structurally, alginate, a natural anionic biopolymer, is a linear hydrophilic polysaccharide consisting of D-mannuronic acid (M) and L-guluronic acid (G) units. The units are present in the form of blocks with a variable M/G ratio [63], either as continuous G chain segments (GGGG), M chain segments (MMMM), or alternating MGMG chain segments [1,64]. It is considered that only the G unit is involved in multivalent ion-induced cross-linking of alginate, and a high G content improves the mechanical strength of alginatebased hydrogels [1].…”

“…Diabetes mellitus (DM) represents a group of chronic metabolic diseases characterized by defective insulin secretion and insulin resistance, which determines increased blood glucose, a condition called hyperglycemia. In addition, hyperglycemia is frequently found associated with various complications, such as diabetic neuropathy, retinopathy, cardiomyopathy and nephropathy, leading to loss of sensation in the lower extremities, blindness, renal failure, chronic wounds and lower extremity amputations [1].…”

“…In contrast to sponges and conventional bandages that only cover the wound and absorb its exudate, natural polymeric hydrogels are considered highly suitable candidates for diabetic wound dressings due to their good biocompatibility and antibacterial properties [1]. They can provide a moist environment, a microporous structure ensuring a good milieu for gas exchange and nutrient transport and a suitable environment mimicking the composition and/or structure of the extracellular matrix (ECM) for cell proliferation and migration [11].…”

Injectable and self-healable nano-architectured hydrogel for NIR-light responsive chemo- and photothermal bacterial eradication

“…21 On the other hand, hydrogel dressings represent significant advancements in treating atypical wounds. 22 Nevertheless, these materials suffer from prolonged gelation time, lack mechanical strength, and an absence of natural extracellular matrix (ECM)-like components. The introduction of additional ion cross-linked components such as sodium alginate (SA) can improve the stability of the system by prolonging the degradation time, improving the mechanical strength, and entrapping polydopamine (PDA) particles and short-filaments (SFs), preventing their escape and deaccelerate drug release, targeting more sustained kinetics.…”

An Immunomodulatory Hydrogel by Hyperthermia‐Assisted Self‐Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics

“…[ 3 ] The number of diabetic patients worldwide is rapidly increasing, while the lack of effective therapeutic strategies underscores the utmost importance of discovering new therapeutic approaches for DFU wound healing. [ 4 ]…”