An Intermediate Unit‐Mediated, Continuous Structural Inheritance Strategy for the Dilemma between Injectability and Robustness of Hydrogels

Abstract

Hydrogels with injectability and robustness have great promise in clinical practice. However, current injectable hydrogels are usually mechanically weak. Here, an idea, "preformed hydrogel reversion", is proposed to develop robust injectable hydrogels through an intermediate unit-mediated, continuous structural inheritance strategy. In this strategy, robust preformed hydrogels are physically disassembled into intermediate injectable structure-inherited microgels (SIMs), and upon encountering water in physiological environment, the SIMs can construct a macroscopical robust structure with the driving force of hydrogen bonds (H-bonds). The physical disassembly and construction process enables the inheritance of robust structures through SIMs, thereby realizing both excellent injectability and robustness. Beyond that, the SIMs also exhibit long-term storage stability and convenient usability. Using protein drug loading and hemostasis as examples, it is demonstrated that the SIM system shows superiorities in biomedical applications. The proposed idea of "preformed hydrogel reversion" can open new horizons for developing robust injectable hydrogels for diverse applications.

Temperature-Responsive Aldehyde Hydrogels with Injectable, Self-Healing, and Tunable Mechanical Properties

“…Hydrogels have been used in a range of biomedical applications, including drug delivery, three-dimensional (3D) cell culture, and tissue engineering, due to their 3D cross-linked polymer networks and high water retention that show striking resemblance to the natural extracellular matrix (ECM). − Along with the increasing demands from current and future biomedical materials, intelligent hydrogels with injectability and self-healing capacity have attracted much interest due to their advantages in minimizing tissue invasion and increasing reliability and durability during the implantation process. − Generally, dynamic covalent chemistries (e.g., phenylboronic ester complexation, , disulfide bond, and Schiff base , ) are effective strategies to fabricate injectable and self-healing hydrogels due to the stimuli-responsive reversibility and shear-shinning properties of dynamic covalent linkages. , However, these dynamic covalently bonded hydrogels usually change their chemical, physical, and mechanical properties in situ after injection because rebuilding of the dynamic covalent bonds is not as rapid as the injection process. , Moreover, due to the ambiguity between injectability and robustness, the injectable capacity of these hydrogels is usually attributed to their shear-shinning viscosity or relevant weak mechanical strength (<0.1 MPa), which contradicts the requirements of implanted hydrogels that need high viscosity and durability to withstand physiological conditions. − To address this challenge, considerable efforts toward fabricating hydrogels with excellent injectability while retaining adaptive mechanical performance and self-healing capacity are undergoing.…”

Smart Hydrogels Bearing Transient Gel–Sol–Gel Transition Behavior Driven by a Biocompatible Chemical Fuel

“…In our case, all the materials we used as well as the waste, glucose, seem non-toxic. To confirm this, we tested the biocompatibility of our hydrogels by the Cell Counting Kit-8 (CCK-8) assay and live/dead staining using murine fibroblasts cells (L929). − Different contents of the PAA–C 18 /α-amylase hydrogels and recovered PAA–C 18 /α-amylase hydrogels fueled by 3.0 equiv of γ-CD were incubated with the cell culture medium for 72 h at 37 °C, which were used for cell culture (L929 cells) after leaching. The CCK-8 assay was first performed to test the metabolic activity of the cells treated with hydrogels.…”

Self-Healing Injectable Hydrogels for Tissue Regeneration

“…A hydrogen bond involves a donor and acceptor, which are typically a hydrogen-bonded electronegative atom and another electronegative atom in its vicinity. Several strategies have been developed for the design of self-healing injectable hydrogels that rely on hydrogen bonds. − A prominent example is the linking of ureido-pyrimidinone (UPy) units to a polymer chain via alkyl-urea spacers. , This reaction has a k eq of 6 × 10 7 M –1 (measured in chloroform at 25 °C) . In water, hydrogen bonds need to be shielded from competing hydrogen-bonding water molecules to be effective cross-linkers for hydrogels.…”

“…An emerging approach for the design of self-healing injectable hydrogels is based on the use of particles as building blocks. In this strategy, hydrogels are formed through 3D assembly or jamming of colloidal (nano)­particles (nanometers to a few micrometers) ,,− or larger microgels (few to several micrometers). ,− Generally, hydrogels made of colloidal particles are referred to as colloidal hydrogels, whereas those assembled from larger microgels are termed granular hydrogels. Hydrogels based on colloidal/granular building blocks have the potential to be more dynamic compared to monolithic hydrogels, which can be favorable for dynamic biological phenomena such as cell ingrowth. , Although inorganic and/or nonswollen polymeric particles can also be employed to form colloidal hydrogels, ,− the particulate building blocks utilized in both colloidal and granular hydrogels are usually of organic nature.…”

“…For instance, highly cross-linked hydrogels are generally not self-healing and injectable. However, smaller microgel particles made from the same material and type of cross-links may very well be self-healing and injectable . Following this approach, several self-healing injectable colloidal hydrogels have been developed based on colloidal hydrogel particles.…”