Interpenetrating Network Hydrogels Research Articles

Localized Ionic Reinforcement of Double Network Granular Hydrogels.

Nature produces soft materials with fascinating combinations of mechanical properties. For example, the mussel byssus embodies a combination of stiffness and toughness, a feature that is unmatched by synthetic hydrogels. Key to enabling these excellent mechanical properties are the well-defined structures of natural materials and their compositions controlled on lengths scales down to tens of nanometers. The composition of synthetic materials can be controlled on a micrometer length scale if processed into densely packed microgels. However, these microgels are typically soft. Microgels can be stiffened by enhancing interactions between particles, for example through the formation of covalent bonds between their surfaces or a second interpenetrating hydrogel network. Nonetheless, changes in the composition of these synthetic materials occur on a micrometer length scale. Here, 3D printable load-bearing granular hydrogels are introduced whose composition changes on the tens of nanometer length scale. The hydrogels are composed of jammed microgels encompassing tens of nm-sized ionically reinforced domains that increase the stiffness of double network granular hydrogels up to 18-fold. The printability of the ink and the local reinforcement of the resulting granular hydrogels are leveraged to 3D print a butterfly with composition and structural changes on a tens of nanometer length scale.

Wrecking neutrophil extracellular traps and antagonizing cancer-associated neurotransmitters by interpenetrating network hydrogels prevent postsurgical cancer relapse and metastases

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

Interpenetrating network based on soybean protein isolate and carboxymethyl chitosan: Investigation of intermolecular reaction mechanism, physicochemical stability and in vitro release properties of the hydrogel

In this study, interpenetrating network (IPN) hydrogels were constructed from soybean protein isolate (SPI) and carboxymethyl chitosan (CMCS) using TGase and genipin (GP) as cross-linking agents. And the influence of IPN formation on the physicochemical properties of hydrogels was illuminated. Multispectral analyses showed that there was a strong interaction between SPI and CMCS, which also promoted the increase of disulfide bonds and hydrophobic interactions in the hydrogels. The IPN was the densest when the addtion of SPI and CMCS were 10% and 3%, respectively. Meanwhile, this structure endowed the hydrogels with good mechanical properties and allowed them to exhibit thixotropy in rheological tests. The LF-NMR results showed that the IPN had a strong binding ability with water molecules and could effectively maintain the water in the hydrogel after freeze-thaw. Moreover, SPI-CMCS IPN hydrogels were pH responsive. This enabled it to adjust its own structure when pH changed, and to achieve controlled release of bioactives during simulated in vitro digestion. Overall, the results of this study showed that the IPN network formed by SPI and CMCS can effectively improve the performance of hydrogel. These results demonstrated the potential of SPI and CMCS as hydrogel synthesizers and provided a theoretical basis for the application of SPI-CMCS IPN hydrogel.

In vitro and in vivo investigation of chitosan/silk fibroin injectable interpenetrating network hydrogel with microspheres for cartilage regeneration

Articular cartilage is an avascular and almost acellular tissue with limited self-regenerating capabilities. Although injectable hydrogels have garnered a lot of attention as a promising treatment, a biocompatible hydrogel with adequate mechanical properties is yet to be created. In this study, an interpenetrating network hydrogel comprised of chitosan and silk fibroin was created through electrostatic and hydrophobic bonds, respectively. The polymeric network of the scaffold combined an effective microenvironment for cell activity with enhanced mechanical properties to address the current issues in cartilage scaffolds. Furthermore, microspheres (MS) were utilized for a controlled release of methylprednisolone acetate (MPA), around ~75 % after 35 days. The proposed scaffolds demonstrated great mechanical stability with ~0.047 MPa compressive moduli and ~145 kPa compressive strength. Moreover, the degradation rate of the samples (~45 % after 35 days) was optimized to match neo-cartilage formation. Furthermore, the use of natural biomaterials yielded good biocompatibility with ~76 % chondrocyte viability after 7 days. According to gross observation after 12 weeks the defect site of the treated groups was filled with minimally discernible boundary. These results were confirmed by histopathology assays were the treated groups showed higher chondrocyte count and collagen type II expression.

Underwater sensors based on dual dynamically crosslinked hydrogels with excellent anti-swelling and adhesive properties

Hydrogel-derived flexible sensors have fascinating applications in the fields of wearable electronics and electronic skin. Nevertheless, the fabrication of underwater sensors is still restricted due to the underwater instability and the poor adhesion in an aquatic environment. In this work, a dynamic physical/chemical dual crosslinked poly (acrylic acid-co-lauryl methacrylate) and polyvinyl alcohol interpenetrating network hydrogel was successfully prepared to overcome the above issues. The as-prepared hydrogels exhibited prior stretchability (2310% strain), good self-healing performance (83% healing efficiency within 36 h), remarkable underwater instability (23% of equilibrium swelling ratio), and long-term underwater adhesion (65.4 kPa of adhesive strength in water for 24 h). The as-prepared hydrogel strain sensor features excellent sensing performance (GF = 4.83) and a wide sensing range of 1%–1000%. Due to its excellent flexibility, strong adhesion, and high strain sensitivity, the prepared hydrogel can be conveniently used for the real-time monitoring of various human movements, including pronounced joint movements and subtle muscle vibrations. Furthermore, the hydrogel-based sensor with good and stable mechanical, electrical, and adhesive properties in an aquatic environment can accomplish effective signal transmission underwater via the combination of body movement and the Morse code.

3D Printable Polyelectrolyte Complex‐Integrated Interpenetrating Network Hydrogels with Customizable Mechanical Strength and pH‐Responsiveness

3D Printable Polyelectrolyte Complex‐Integrated Interpenetrating Network Hydrogels with Customizable Mechanical Strength and pH‐Responsiveness

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium–indium LM particles were first stabilized with 1,2-Distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. Statement of significanceOur research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Free-standing and flexible polyvinyl alcohol-sodium alginate-polypyrrole electrodes based on interpenetrating network hydrogels

Flexible supercapacitors (FSCs) have attracted much attention due to their strong mechanical flexibility, wearability and portability, which greatly rely on the employed flexible electrodes. The conductive polymer hydrogels with excellent flexibility, processability and capacitive performance are one of the most promising candidates, which are still limited by their poor mechanical properties. Constructing robust interpenetrating polymer networks (IPN) is an effective approach to promote their mechanical properties. Herein, interpenetrating polyvinyl alcohol (PVA)-sodium alginate (SA)-polypyrrole (PPy) hydrogels are prepared by the freeze–thaw and in-situ polymerization method. The IPN structure composed of PVA and SA not only enhances the mechanical properties of hydrogels, but also provides substantial active sites for electrochemical reactions. Moreover, the hydrogen-bonding interaction between different components in the PVA-SA-PPy hydrogel boosts the charge/ion transfer. The optimal PVA-SA-PPy hydrogels show an elongation at break of 380 %, a tensile strength of 1.5 MPa, and a specific capacitance of 2646 mF cm−2 at 2 mA cm−2. The symmetric PVA-SA-PPy FSCs show an energy density of 96.7 μWh cm−2 at a power density of 999.9 μW cm−2, and the capacitance retention is 66.3 % after 10,000 cycles. These exceptional mechanical and electrochemical properties make the PVA-SA-PPy hydrogels a promising candidate for FSCs.

The three-dimensional culture of L929 and C2C12 cells based on SPI-SA interpenetrating network hydrogel scaffold with excellent mechanical properties.

Cell-cultured meat, which is obtained by adsorbing cells on the three-dimensional scaffold, is considered a potential solution to animal welfare issues. Edible and safe cell-cultured meat scaffolds are a key part of its research. Soy protein isolate (SPI) hydrogel has a three-dimensional network structure and has been studied for L929 cell culture because of its non-toxicity and biocompatibility. However, the toughness and mechanical properties of SPI hydrogel are not enough to bear the requirements of cell cultivation. In this paper, sodium alginate (SA) was added to SPI hydrogel, and the interpenetrating network (IPN) technology was used to construct SPI-SA IPN hydrogel by transglutaminase and Ca2+ double crosslinking method. SPI-SA IPN hydrogel has excellent mechanical properties, structural stability and biodegradable performance than SPI hydrogel. The bio-compatibility and degradability of L929 and C2C12 cells on SPI-SA IPN hydrogel were studied by cytotoxicity, trypan blue and living/dead cell staining, and the growth law of the hydrogel as a scaffold for cell culture was analyzed. The results showed that L929/C2C12 cells can proliferate normally and adhere in hydrogel and have good bio-compatibility. L929 cells with size about 20-50µm have better adhesion and growth abilities on SPI-SA IPN hydrogel than C2C12 cells with 100-300µm. Therefore, the SPI-SA IPN hydrogel is non-toxic and supports the growth of cells in the pores of the material. This study provides a reference for the application of SPI-SA IPN hydrogels in vitro cell growth.

Interpenetrating network hydrogels for studying the role of matrix viscoelasticity in 3D osteocyte morphogenesis.

During bone formation, osteoblasts are embedded in a collagen-rich osteoid tissue and differentiate into an extensive 3D osteocyte network throughout the mineralizing matrix. However, how these cells dynamically remodel the matrix and undergo 3D morphogenesis remains poorly understood. Although previous reports investigated the impact of matrix stiffness in osteocyte morphogenesis, the role of matrix viscoelasticity is often overlooked. Here, we report a viscoelastic alginate-collagen interpenetrating network (IPN) hydrogel for 3D culture of murine osteocyte-like IDG-SW3 cells. The IPN hydrogels consist of an ionically crosslinked alginate network to tune stress relaxation as well as a permissive collagen network to promote cell adhesion and matrix remodeling. Two IPN hydrogels were developed with comparable stiffnesses (4.4-4.7 kPa) but varying stress relaxation times (t1/2, 1.5 s and 14.4 s). IDG-SW3 cells were pre-differentiated in 2D under osteogenic conditions for 14 days to drive osteoblast-to-osteocyte transition. Cellular mechanosensitivity to fluid shear stress (2 Pa) was confirmed by live-cell calcium imaging. After embedding in the IPN hydrogels, cells remained highly viable following 7 days of 3D culture. After 24 h, osteocytes in the fast-relaxing hydrogels showed the largest cell area and long dendritic processes. However, a significantly larger increase of some osteogenic markers (ALP, Dmp1, hydroxyapatite) as well as intercellular connections via gap junctions were observed in slow-relaxing hydrogels on day 14. Our results imply that fast-relaxing IPN hydrogels promote early cell spreading, whereas slow relaxation favors osteogenic differentiation. These findings may advance the development of 3D in vivo-like osteocyte models to better understand bone mechanobiology.

A 3D culture method based on interpenetrating hydrogels induced by cells into skeletal muscle tissue in vitro

The combination of muscle cells and soft robotics technology has led to the rapid development of biohybrid robots in recent years. Muscle-driven systems had advantages such as joint flexibility, self-repair, and multi-signal perception, demonstrating unique advantages as an effective technological solution for robot drive systems. Current research has many shortcomings in material properties and muscle stability in 3D muscle tissue cultured in vitro, making it difficult to successfully apply the technology. In this study, we developed a new type of interpenetrating hydrogel network that, combined with 3D cell culture and tissue-induced culture, enabled 3D muscle tissue culture in a hydrogel environment and induced differentiation in muscle tissue. The results of this research provided a foundation for future studies on in vitro muscle tissue culture and the implementation of robots in this field.

Construction of a Decellularized Multicomponent Extracellular Matrix Interpenetrating Network Scaffold by Gelatin Microporous Hydrogel 3D Cell Culture System.

Interface tissue repair requires the construction of biomaterials with integrated structures of multiple protein types. Hydrogels that modulate internal porous structures provide a 3D microenvironment for encapsulated cells, making them promise for interface tissue repair. Currently, reduction of intrinsic immunogenicity and increase of bioactive extracellular matrix (ECM) secretion are issues to be considered in these materials. In this study, gelatin methacrylate (GelMA) hydrogel is used to encapsulate chondrocytes and construct a phase transition 3D cell culture system (PTCC) by utilizing the thermosensitivity of gelatin microspheres to create micropores within the hydrogel. The types of bioactive extracellular matrix protein formation by chondrocytes encapsulated in hydrogels are investigated in vitro. After 28 days of culture, GelMA PTCC forms an extracellular matrix predominantly composed of collagen type II, collagen type I, and fibronectin. After decellularization, the protein types and mechanical properties are well preserved, fabricating a decellularized tissue-engineered extracellular matrix and GelMA hydrogel interpenetrating network hydrogel (dECM-GelMA IPN) consisting of GelMA hydrogel as the first-level network and the ECM secreted by chondrocytes as the second-level network. This material has the potential to mediate the repair and regeneration of tendon-bone interface tissues with multiple protein types.

Development of polymeric IPN hydrogels by free radical polymerization technique for extended release of letrozole: Characterization and toxicity evaluation

Abstract This research study’s objective was to formulate interpenetrating pH-sensitive polymeric networks interpenetrating networks (IPNs) based on hydroxypropylmethylcellulose (HPMC)/Primojel for use in the treatment of various malignant conditions. For controlled release, letrozole (LTZ) was selected as a model drug in HPMC and Primojel-based IPN hydrogels. HPMC and Primojel based IPN hydrogels were fabricated through the free radical polymerization method by utilizing HPMC and Primojel as polymers, methacrylic acid as monomer, ammonium persulfate as initiator, and methylenebisacrylamide as cross-linker. For structural characterization, various techniques such as Fourier transform infrared spectroscopy, Scanning electron microscopy (SEM), DSC, TGA, and Powder x-ray diffraction (PXRD) were applied to IPN samples. In vitro and swelling studies were also employed to observe the response of these polymeric networks against 1.2 and 7.4 pH. TGA and DSC of an optimized loaded formulation possess better thermal stability as compared to individual drug. PXRD depicted minor crystallinity and a significant amorphous nature. SEM images show that polymeric networks possess an uneven and porous surface. Significant swelling and enhanced in-vitro outcomes at a high pH of 7.4 confirmed the IPN pH responsive properties. Toxicological studies performed on rabbits revealed no harm in the results. Thus, IPN based on HPMC/Primojel was successfully synthesized and can be used for LTZ’s controlled release.

Inorganic metal salts as additives in the design of cellulose/arabinogalactan hydrogels for prolonged delivery of simvastatin in simulated bio‐fluids

AbstractIn this study, carboxymethylcellulose and arabinogalactan were used to create an interpenetrating network (IPN) hydrogel system in the presence of AlCl3 alone or in combination with ZnSO4 salts. Ionotropic gelation caused the polymer sol droplets to transform into hydrogel particles in the presence of salts. The impact of salts on hydrogel properties was evaluated in terms of morphology, drug entrapment efficiency, swelling, and drug release kinetics. The cellulose IPN hydrogel particles containing 50% arabinogalactan looked spherical with evidence of surface folding when treated with AlCl3. Surface folding was reduced by an additional treatment with ZnSO4. Following treatment of the IPN particles with dual salts, a maximum drug entrapment efficiency of 88.77% was obtained. Surface erosion, as seen with aluminum‐IPN hydrogel particles, was minimized with the use of mixed salts as gelation medium. Furthermore, the use of mixed salts allowed the hydrogel particles to swell and consistently release simvastatin in simulated gastrointestinal fluids for up to 9 h. Thermal and x‐ray analyses revealed that the crystallinity of the drug reduced considerably after entrapment in the IPN hydrogel matrix. The infrared spectra analysis did not indicate any evidence of drug polymer interaction. The release of drug from the IPN hydrogel particles followed non‐Fickian diffusion mechanism. The dual metallic salts were found to be effective in creating physically stable cellulose‐arabinogalactan IPN hydrogel particles for sustained release of simvastatin in a varying pH environment of gastrointestinal tract.Highlights Dual inorganic salts allowed synthesis of cellulose/arabinogalactan hydrogel Additional use of ZnSO4 improved surface morphology of hydrogel particles Compatible environment of hydrogels allowed more than 88% drug entrapment Concentration of neutral arabinogalactan was crucial in dictating drug release Mixed salts controlled swelling and release of simvastatin from hydrogels

Fabrication and rheological properties of a novel interpenetrating network hydrogel based on sage seed hydrocolloid and globulin from the hydrocolloid extraction by-product

In this study, interpenetrating polymer network hydrogels were developed based on sage seed gum (SSG) and globulin protein (Glo) extracted from the mucilage-free seeds. By combining Glo hydrogel with the SSG network the inherent weak gelation of the single SSG system was compensated. As the fraction of Glo increased, various properties of the interpenetrating polymer network (IPN) hydrogels improved substantially. Electrophoretic analysis under reducing conditions showed that Glo dissociated into subunits of approximately 30 kDa and 20 kDa, suggesting it comprises 11S globulin. FTIR spectrum revealed new peaks at 1645 cm−1 and 1537 cm−1 in the amide I and II regions, respectively, for the IPN hydrogels, indicating interactions between two hydrogel networks. Based on the weight loss measurements, the IPN hydrogels exhibited lower mass loss, particularly at higher Glo fractions up to 6 %. The IPN hydrogels also displayed enhanced elasticity, pseudoelasticity, thixotropy, and creep resistance compared to SSG hydrogel, indicating suitability for food, pharmaceutical, and biomedical applications. More broadly, this research provides a sustainable strategy toward innovative material development while advancing bio-based hydrogels.

Construction of transparent PAM/PVA interpenetrating network hydrogel for designing fireproof glass with superior heat insulation and aging resistance

The decorative and fireproof performance degradation of the grouting fireproof glass exposed to UV irradiation limits its application in the fire protection of buildings. To solve this issue, a transparent polyacrylamide/polyvinyl alcohol (PAM/PVA) interpenetrating network hydrogel was designed to prepare grouting fireproof glass with enhanced theheat insulation and anti-aging properties. The results show that the light transmittance of PAM/PVA interpenetrating network hydrogel decreases with the increased content of PVA, and a proper content of PVA in the PAM/PVA interpenetrating network is beneficial to maintain high optical transparency in the resulting hydrogel. Heat insulation test shows that the PAM/PVA interpenetrating network improves the water-locking ability of the resulting hydrogels, and the fireproof glass containing 3 wt% PVA shows the lowest backside temperature of 92.6 °C at 3600 s, which is 51.9% lower than that of fireproof glass with PAM only. Thermogravimetric (TG) and differential scanning calorimetry (DSC) analysis show that the PAM/PVA interpenetrating network hydrogel improves the thermal stability and charring ability of hydrogel, and the hydrogel containing 3 wt% PVA exhibits the best charring effect among the samples, showing the highest residual yield of 39.2 % at 800 °C. The analyses of decomposition products and char residues show that the PAM/PVA interpenetrating network hydrogel can extend the heat absorption process of water evaporation and improve the gas flame retardant efficiency. Accelerated aging test shows that the presence of PVA greatly slows down the blistering and yellowing phenomenon of fireproof glass, thus endowing the fireproof glass with the super durability of fire resistance. Especially, the backside temperature at 3600 s and light transmittance of the sample containing 2 wt% PVA after 168 h aging test only changed 19.2 °C and 1.9 %, respectively, compared to the those of unaged sample.

Dual Photo‐Enhanced Interpenetrating Network Hydrogel with Biophysical and Biochemical Signals for Infected Bone Defect Healing (Adv. Healthcare Mater. 25/2023)

Dual Photo‐Enhanced Interpenetrating Network Hydrogel with Biophysical and Biochemical Signals for Infected Bone Defect Healing (Adv. Healthcare Mater. 25/2023)

Preparation of polyethylene glycol/polyacrylamide interpenetrating network hydrogel for simultaneously enhancing the fire protection and aging resistance of fireproof glass

AbstractTo enhance the flame retardancy and aging resistance of grouting fireproof glass, different molecular weights of polyethylene glycol (PEG) were mixed with acrylamide (AM) to construct interpenetrating network hydrogels, then the obtained hydrogels were mixed with flame retardants to prepare a series of transparent flame‐retarded hydrogels applied in the fireproof glass. The effects of PAM/PEG hydrogel with varying PEG molecular weight on the optical transparency, heat insulation and aging resistance of fireproof glass were investigated. Optical transparency analysis shows that the light transmittance of grouting fireproof glass decreases with the increase of PEG molecular weight in the PAM/PEG interpenetrating network. Fire tests show that PAM/PEG hydrogel significantly enhances the heat insulation and aging resistance of the grouting fireproof glass compared to the single PAM network hydrogel. The flame‐retarded and anti‐aging effects of PAM/PEG hydrogel in the fireproof glass varies with the PEG molecular weight, and the order is PAM/PEG2000 > PAM/PEG1500 > PAM/PEG1000 > PAM/PEG800. Accelerated aging test shows that PAM/PEG interpenetrating network hydrogel is less affected by aging conditions and exerts durable heat insulation and transmittance. Especially, the backside temperature of 3600 s and transmittance of PAM/PEG2000 system after 264 h aging test only changed 38.3°C and 1.3%, respectively, compared to the unaged PAM/PEG2000 system.

3D Printing of Interpenetrating Network Flexible Hydrogels with Enhancement of Adhesiveness.

3D printing of hydrogels has been widely explored for the rapid fabrication of complex soft structures and devices. However, using 3D printing to customize hydrogels with both adequate adhesiveness and toughness remains a fundamental challenge. Here, we demonstrate mussel-inspired (polydopamine) PDA hydrogel through the incorporation of a classical double network (2-acrylamido-2-methylpropanesulfonic acid) PAMPS/(polyacrylamide) PAAm to achieve simultaneously tailored adhesiveness, toughness, and biocompatibility and validate the 3D printability of such a hydrogel into customized architectures. The strategy of combining PDA with PAMPS/PAAm hydrogels leads to favorable adhesion on either hydrophilic or hydrophobic surfaces. The hydrogel also shows excellent flexibility, which is attributed to the reversible cross-linking of PDA and PAMPS, together with the long-chain PAAm cross-linking network. Among them, the reversible cross-linking of PDA and PAMPS is capable of dissipating mechanical energy under deformation. Meanwhile, the long-chain PAAm network contributes to maintaining a high deformation capability. We establish a theoretical framework to quantify the contribution of the interpenetrating networks to the overall toughness of the hydrogel, which also provides guidance for the rational design of materials with the desired properties. Our work manifests a new paradigm of printing adhesive, tough, and biocompatible interpenetrating network hydrogels to meet the requirements of broad potential applications in biomedical engineering, soft robotics, and intelligent and superabsorbent devices.

Dual Photo-Enhanced Interpenetrating Network Hydrogel with Biophysical and Biochemical Signals for Infected Bone Defect Healing.

The healing of infected bone defects (IBD) is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, vascularization, and osteogenesis. Based on the theory that bone healing is regulated by both biochemical and biophysical signals, in this study, a copper doped bioglass (CuBGs)/methacryloyl-modified gelatin nanoparticle (MA-GNPs)/methacrylated silk fibroin (SilMA) hybrid hydrogel is developed to promote IBD healing. This hybrid hydrogel demonstrates a dual-photocrosslinked interpenetrating network mechanism, wherein the photocrosslinked SilMA as the main network ensures structural integrity, and the photocrosslinked MA-GNPs colloidal network increases strength and dissipates loading forces. In an IBD model, the hydrogel exhibits excellent biophysical characteristics, such as adhesion, adaptation to irregular defect shapes, and in situ physical reinforcement. At the same time, by sequentially releasing bioactive ions such as Cu2+ , Ca2+ , and Si2+ ions from CuBGs on demand, the hydrogel spatiotemporally coordinates antibacterial, immunomodulatory and bone remodeling events, efficiently removing infection and accelerating bone repair without the use of antibiotics or exogenous recombinant proteins. Therefore, the hybrid hydrogel can be used as a simple and effective method for the treatment of IBD.