Bioinspired Hydrogel Research Articles

Y chromosome linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.

Aortic valve stenosis (AVS) is a progressive disease wherein males more often develop valve calcification relative to females that develop valve fibrosis. Valvular interstitial cells (VICs) aberrantly activate to myofibroblasts during AVS, driving the fibrotic valve phenotype in females. Myofibroblasts further differentiate into osteoblast-like cells and produce calcium nanoparticles, driving valve calcification in males. We hypothesized the lysine demethylase UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked) decreases methylation uniquely in male VICs responding to nanoscale extracellular matrix cues to promote an osteoblast-like cell phenotype. Here, we describe a hydrogel biomaterial cell culture platform to interrogate how nanoscale cues modulate sex-specific methylation states in VICs activating to myofibroblasts and osteoblast-like cells. We found UTY modulates the osteoblast-like cell phenotype in response to nanoscale cues uniquely in male VICs. Overall, we reveal a novel role of UTY in the regulation of calcification processes in males during AVS progression.

Preparation and properties of biomimetic bone repair hydrogel with sandwich structure.

One of the critical factors that determines the biological properties of scaffolds is their structure. Due to the mechanical and structural discrepancies between the target bone and implants, the poor internal architecture design and difficulty in degradation of conventional bone implants may cause several adverse outcomes. To date, many scaffolds, such as 3-D printed sandwich structures, have been successfully developed for the repair of bone defects; however, the steps of these methods are complex and costly. Hydrogels have emerged as a unique scaffold material for repairing bone defects because of their good biocompatibility and excellent physicochemical properties. However, studies exploring bioinspired hydrogel scaffolds with hierarchical structures are scarce. More efforts are needed to incorporate bioinspired structures into hydrogel scaffolds to achieve optimal osteogenic properties. In this study, we developed a low-cost and easily available hydrogel matrix that mimicked the natural structure of the bone's porous sandwich to promote new bone growth and tissue integration. A comprehensive evaluation was conducted on the microstructure, swelling rate, and mechanical properties of this hydrogel. Furthermore, a 3D finite element analysis was employed to model the structure-property relationship. The results indicate that the sandwich-structured hydrogel is a promising scaffold material for bone injury repair, exhibiting enhanced compressive stress, elastic modulus, energy storage modulus, and superior force transmission.

Bio-Inspired Double-Layered Hydrogel Robot with Fast Response via Thermo-Responsive Effect.

Bio-inspired hydrogel robots have become promising due to their advantage of the interaction safety and comfort between robots and humans, while current hydrogel robots mainly focus on underwater movement due to the hydration-dehydration process of thermo-responsive hydrogels, which greatly limits their practical applications. To expand the motion of the thermo-responsive hydrogel robot to the ground, we constructed a hydrogel robot inspired by a caterpillar, which has an anisotropic double-layered structure by the interfacial diffusion polymerization method. Adding PVA and SA to PNIPAm will cause different conformation transitions. Therefore, sticking the two layers of hydrogel together will form a double-layer anisotropic structure. The ultra-high hydrophilicity of PVA and SA significantly reduces the contact angle of the hydrogel from 53.1° to about 10° and reduces its hydration time. The responsive time for bending 30° of the hydrogel robot has been greatly reduced from 1 h to half an hour through the enhancement of photo-thermal conversion and thermal conductivity via the addition of Fe3O4 nanoparticles. As a result, the fabricated hydrogel robot can achieve a high moving speed of 54.5 mm·h-1 on the ground. Additionally, the fabricated hydrogel has excellent mechanical strength and can endure significant flexibility tests. This work may pave the road for the development of soft robots and expand their applications in industry.

Recent Advances in Smart Self-Assembled Bioinspired Hydrogels: A Bridging Weapon for Emerging Health Care Applications from Bench to Bedside.

Stimuli-responsive low molecular weight hydrogel interventions for Biomedical challenges are a rapidly evolving paradigm in the bottom-up approach recently. Peptide-based self-assembled nano biomaterials present safer alternatives to their non-degradable counterparts as demanded for today's most urged clinical needs.Although a plethora of work has already been accomplished, programming hydrogelators with appropriate functionalities requires a better understanding as the impact of the macromolecular structure of the peptides and subsequently, their self-assembled nanostructures remain unidentified. Henceforth this review focuses on two aspects: Firstly, the underlying guidelines for building biomimetic strategies to tailor scaffolds leading to hydrogelation along with the role of non-covalent interactions that are the key components of various self-assembly processes. In the second section, it is aimed to bring together the recent achievements with designer assembly concerning their self-aggregation behaviour and applications mainly in the biomedical arena like drug delivery carrier design, antimicrobial, anti-inflammatory as well as wound healing materials. Furthermore, it is anticipated that this article will provide a conceptual demonstration of the different approaches taken towards the construction of these task-specific designer hydrogels. Finally, a collective effort among the material scientists is required to pave the path for the entrance of these intelligent materials into medicine from bench to bedside.

Fabrication and Characterization of Quad-Component Bioinspired Hydrogels to Model Elevated Fibrin Levels in Central Nervous Tissue Scaffolds.

Multicomponent interpenetrating polymer network (mIPN) hydrogels are promising tissue-engineering scaffolds that could closely resemble key characteristics of native tissues. The mechanical and biochemical properties of mIPNs can be finely controlled to mimic key features of target cellular microenvironments, regulating cell-matrix interactions. In this work, we fabricated hydrogels made of collagen type I (Col I), fibrin, hyaluronic acid (HA), and poly (ethylene glycol) diacrylate (PEGDA) using a network-by-network fabrication approach. With these mIPNs, we aimed to develop a biomaterial platform that supports the in vitro culture of human astrocytes and potentially serves to assess the effects of the abnormal deposition of fibrin in cortex tissue and simulate key aspects in the progression of neuroinflammation typically found in human pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), and tissue trauma. Our resulting hydrogels closely resembled the complex modulus of AD human brain cortex tissue (~7.35 kPa), promoting cell spreading while allowing for the modulation of fibrin and hyaluronic acid levels. The individual networks and their microarchitecture were evaluated using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Human astrocytes were encapsulated in mIPNs, and negligible cytotoxicity was observed 24 h after the cell encapsulation.

Vat Photopolymerization 3D Printing Hydrogels and Bionic Adhesive Devices: A Minireview

AbstractVivid biological structures with reversible adhesive properties are widely found in nature. Although current biomimicking adhesion systems have attracted extensive attention, unmet challenges remain in terms of excellent adhesion preservation, precise structural fabrication, and good environmental compatibility. By combining advanced vat photopolymerization 3D printing technology with hydrogel materials with excellent environmental adaptability, bioinspired adhesion devices present satisfactory application prospects. Herein, a systematic overview of bioinspired hydrogel adhesion devices from the perspectives of material design, structural design, and fabrication is presented. First, the main types and application prospects of vat photopolymerization 3D printed hydrogels are introduced. Subsequently, the research progress on hydrogel‐based vat photopolymerized 3D printed bionic adhesion devices is detailed. Future developments, such as balancing unmet challenges and expected opportunities, in 3D printable multiscale bionic adhesive devices are presented.

Abundant nucleation sites-available liquid crystal hydrogel mimics bone ECM mineralization to boost osteogenesis

Bone extracellular matrix (ECM) is a unique organic-inorganic composite material derived from highly mineralized liquid crystal (LC) organic substrate. However, it remains a substantial challenge to design bone ECM-like LC materials with sufficient available nucleation sites to mimic the mineralization process of natural bone. Herein, we designed a bioinspired hydrogel with bone ECM-like LC organic substrate and inorganic phosphate mineralization nucleation sites for robust cell biomineralization and bone regeneration. Black phosphorus (BP) nanosheet was firstly loaded by bioactive layered double hydroxide (LDH) based on electrostatic attraction to improve the stability and photothermal performance of BP. Then, the LDH@BP was creatively added into chitin whisker/poly (ethylene glycol) diacrylate (CHW/PEGDA) LC hydrogel, abbreviated as LCgel, to fabricate LCgel/LDH@BP to highly mimic the mineralization microenvironment of bone ECM. The bone ECM-like LC topology of LCgel/LDH@BP is conducive to facilitating cell adhesion, proliferation and osteogenic differentiation. More importantly, the in-situ phosphate mineralization nucleation sites combined with mild hyperthermia induced by BP can further synergistically reinforce biomineralization of cells adhered on bone ECM-like LC substrate, thus substantially promoting cell biomineralization-mediated osteogenesis in vitro and in vivo. This study opens a new insight for the design of bioinspired hydrogel for cell biomineralization-mediated osteogenesis.

Accelerated water harvesting from vapor via a bio-inspired hydrogel pattern.

Accelerated water harvesting from vapor via a bio-inspired hydrogel pattern.

A bioinspired hydrogel with tailored nano-topography and desired mechanical performance for highly efficient solar-driven water purification

Solar-driven interfacial evaporation has emerged as a sustainable and innovative technology for efficient, clean water production.

A bioinspired injectable antioxidant hydrogel for prevention of postoperative adhesion.

Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.

A bioinspired hydrogel carrier with pH/redox dual responsiveness for effective protection and intestinal targeted delivery of probiotics

A bioinspired hydrogel carrier with pH/redox dual responsiveness for effective protection and intestinal targeted delivery of probiotics

Natural and Engineered Isoforms of the Inflammasome Adaptor ASC Form Noncovalent, pH-Responsive Hydrogels.

The protein ASC polymerizes into intricate filament networks to assemble the inflammasome, a filamentous multiprotein complex that triggers the inflammatory response. ASC carries two Death Domains integrally involved in protein self-association for filament assembly. We have leveraged this behavior to create noncovalent, pH-responsive hydrogels of full-length, folded ASC by carefully controlling the pH as a critical factor in the polymerization process. We show that natural variants of ASC (ASC isoforms) involved in inflammasome regulation also undergo hydrogelation. To further demonstrate this general capability, we engineered proteins inspired by the ASC structure that also form hydrogels. We analyzed the structural network of the natural and engineered protein hydrogels using transmission and scanning electron microscopy and studied their viscoelastic behavior using shear rheology. Our results reveal one of the very few examples of hydrogels created by the self-assembly of globular proteins and domains in their native conformation and show that Death Domains can be used alone or as building blocks to engineer bioinspired hydrogels.

Bio-Inspired Far-From-Equilibrium Hydrogels: Design Principles and Applications.

Inspired from dynamic living systems that operate under out-of-equilibrium conditions in biology, developing supramolecular hydrogels with self-regulating and autonomously dynamic properties to further advance adaptive hydrogels with life-like behavior is important. This review presents recent progress of bio-inspired supramolecular hydrogels out-of-equilibrium. The principle of out-of-equilibrium self-assembly for creating bio-inspired hydrogels is discussed. Various design strategies have been identified, such as chemical-driven reaction cycles with feedback control and physically oscillatory systems. These strategies can be coupled with hydrogels to achieve temporal and spatial control over structural and mechanical properties as well as programmable lifetime. These studies open up huge opportunities for potential applications, such as fluidic guidance, information storage, drug delivery, actuators and more. Finally, we address the challenges ahead of us in the coming years, and future possibilities and prospects are identified.

A Bioinspired Injectable, Adhesive And Self-Healing Hydrogel with Dual Hybrid Network for Neural Regeneration After Spinal Cord Injury.

Hydrogel-based regenerated scaffold shows promise as a platform for neural regeneration following spinal cord injury (SCI). Nevertheless, the persistent problem of poor mechanical strength and limited integration with the host tissue still exists. In this study, we developed a bioinspired hydrogel with highly sophisticated features for neural regeneration after SCI. The hydrogel is composed of DOPA-grafted chitosan and a designer peptide, offering a unique set of qualities such as being injectable, having self-healing abilities, and adhering to tissues. Compared to the conventional hydrogel, our hydrogel insured as significant promotion of the immune response modulation and axon regrowth while featuring synapse formation of various neurotransmitters and myelin regeneration. Subsequently, functional recoveries were enhanced, including motor function, sensory function and particularly bladder defect repair. These positive findings demonstrate that the hydrogel has great potential as a strategy for repairing SCI. Moreover, the versatility of this strategy goes beyond neural regeneration and holds promise for tissue regeneration in other contexts. Overall, our proposed hydrogel represented an innovative and multifaceted tool for engineering structures in the biomedical field. This article is protected by copyright. All rights reserved.

Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization

Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.

Diversity of Bioinspired Hydrogels: From Structure to Applications

Hydrogels are three-dimensional networks with a variety of structures and functions that have a remarkable ability to absorb huge amounts of water or biological fluids. They can incorporate active compounds and release them in a controlled manner. Hydrogels can also be designed to be sensitive to external stimuli: temperature, pH, ionic strength, electrical or magnetic stimuli, specific molecules, etc. Alternative methods for the development of various hydrogels have been outlined in the literature over time. Some hydrogels are toxic and therefore are avoided when obtaining biomaterials, pharmaceuticals, or therapeutic products. Nature is a permanent source of inspiration for new structures and new functionalities of more and more competitive materials. Natural compounds present a series of physico-chemical and biological characteristics suitable for biomaterials, such as biocompatibility, antimicrobial properties, biodegradability, and nontoxicity. Thus, they can generate microenvironments comparable to the intracellular or extracellular matrices in the human body. This paper discusses the main advantages of the presence of biomolecules (polysaccharides, proteins, and polypeptides) in hydrogels. Structural aspects induced by natural compounds and their specific properties are emphasized. The most suitable applications will be highlighted, including drug delivery, self-healing materials for regenerative medicine, cell culture, wound dressings, 3D bioprinting, foods, etc.

Enriching and Smart Releasing Curcumin via Phenylboronic Acid‐Anchored Bioinspired Hydrogel for Diabetic Wound Healing

Diabetic wounds suffer from bacterial infections, reactive oxygen species, and inflammatory reactions. Curcumin (Cur) is a natural diketone with antibacterial, anti‐inflammatory, antioxidant activities, but poor water solubility and toxicity at high local concentration. Herein, inspired by the oxygen transport process of red blood cells via the dynamic interaction of hemoglobin and oxygen, phenylboronic acid (PBA)‐anchored hydrogel (GOHA‐PBA) is utilized to achieve active enrichment and smart release of Cur, which can reverse the inflammatory microenvironment and promote wound healing. First, PBA‐modified gelatin (Gel‐PBA) and oxidized hyaluronic acid (OHA) crosslink and form GOHA‐PBA by borate ester reaction and Schiff base reaction. GOHA‐PBA possesses excellent curcumin loading efficiency with 130 000 times than that in water and forms Cur‐laden GOHA‐PBA (GOHA‐Cur). GOHA‐Cur has injectability, self‐healing, and self‐adaptive properties, which are conducive to surgical procedure. GOHA‐Cur owns reversible adhesion properties, facilitating it be peeled off and remove harmful substances, including excess glucose, acids, bacteria, and ROS at the wounds. GOHA‐Cur can pH and glucose responsively release Cur; hence, it shows excellent antibacterial, antioxidant, anti‐inflammatory effects in vitro. Animal experiments show that GOHA‐Cur can inhibit inflammation and promote wound regeneration. This study can provide a valuable concept for Cur delivery and diabetic wound healing.

Bio-inspired Structure-editing Fluorescent Hydrogel Actuators for Environment-interactive Information Encryption.

Many living organisms have the superb structure-editing capacity for better adaptation in dynamic environments over the course of their life cycle. However, it's still challenging to replicate such natural structure-editing capacity into artificial hydrogel actuating systems for enhancing environment-interactive functions. Herein, we learn from the metamorphosis development of glowing octopus to construct proof-of-concept fluorescent hydrogel actuators with life-like structure-editing capacity by developing a universal stepwise inside-out growth strategy. These actuators could perform origami-like 3D shape deformation and also enable the postnatal growth of new structures to adapt additional actuating states for different visual information delivery by using different environment keys (e.g., temperature, pH). This study opens previously unidentified-avenues of bio-inspired hydrogel actuators/robotics and extends the potential uses for environment-interactive information encryption.

Bio-inspired hydrogel actuator with rapid self-strengthening behavior

Inspired by intelligent biomaterials which often have flexible responsiveness to multiple environmental cues and strengthen their mechanical properties by trainings, emerging soft actuators require programmable manipulation. Currently, the integration of such characteristics as rapid self-strengthening, strain-adaptive stiffening and smart actuation, into a single hydrogel actuator is urgently needed. Here, we report a self-strengthened hydrogel actuator based on the semi-interpenetrating polymer network consisting of polyvinyl alcohol (PVA) and poly(N-isopropylacrylamide) (PNIPAm), which can display diverse programmable actuations by responding to temperature/salt stimuli. In the design, the layer of freeze-thawed PNIPAm/PVA (PPGel-F) is assembled with another original PNIPAm/PVA hydrogel layer (PPGel) into one device. By taking advantage of the PVA crystalline nanofibrils in the PPGel-F matrix, the differentiated swelling degree across the bilayer structure gives rise to asymmetric deformations and the resultant shape transformation. Moreover, upon the mechanical training with less than 100 cycles, the anisotropic arrangement of PVA nanofibrils through strong hydrogen bonding interactions can swiftly immobilize the amorphous polymer chains orientation along the tensile direction. This enhances the strain-induced crystallization, thereby generating the rapid self- strengthening behavior. The proposed work provides potential solution for constructing dynamically adaptive hydrogel systems that can mimic biological tissues for more intelligent soft robotics and bionic research.

Injectable hydrogels of recombinant human collagen type III and chitosan with antibacterial and antioxidative activities for wound healing.

Designing a smart hydrogel to accelerate skin tissue regeneration at wound sites and restore the tissue function is highly desirable in clinical applications. In this study, a series of hydrogels with promising antioxidative and antibacterial traits based on recombinant human collagen type III (rhCol III), which is an emerging biomaterial, and chitosan (CS) were fabricated. The rhCol III-CS hydrogel could realize rapid gelation at wound locations and completely cover irregular wounds. Additionally, the hydrogel facilitated the proliferation and migration of cells and showed potent antibacterial efficacy against both strains, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro. Significantly, the rhCol III-CS2 hydrogel increased the deposition of collagen, thereby accelerating full-thickness wound healing. Collectively, this bioinspired hydrogel was a promising multifunctional dressing to reconfigure the damaged tissue without additional drugs, exogenous cytokines, or cells, providing an effective strategy for the repair and regeneration of skin wounds.