Interpenetrating Network Hydrogels Research Articles

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

AbstractHerein, a novel 3D printable ink designed for the fabrication of interpenetrating polymer network (IPN) hydrogels is introduced, ingeniously integrating a polyelectrolyte complex (PEC) of hyaluronic acid (HA) and chitosan (CS) with a photo‐crosslinkable P(OEGMA‐co‐EGDEMA) polymer. Initially, the carboxyl group of HA is modified with a photo‐labile ortho‐nitrobenzyl group, preventing premature PEC formation during 3D ink formulation. Subsequent UV illumination via digital light processing (DLP) simultaneously triggers the photo‐deprotection of the carboxyl group of HA and the photopolymerization of OEGMA crosslinked hydrogel, together creating a PEC‐integrated IPN hydrogel. Comprehensive characterizations, including NMR, IR, UV/Vis, TGA, DSC, SEM, and mechanical tests are conducted to evaluate the structural, morphological, and rheological properties of these hydrogels. Furthermore, adjustments to the composition of the 3D ink enable the production of hydrogels with a spectrum of mechanical strength and elastic modulus ranging from 1 to 10 kPa. The resultant PEC‐IPN hydrogels display excellent flexibility, compressive strength, high strain tolerance, pH responsiveness, and thermal stability. In essence, the approach seamlessly merges natural polyelectrolytes with technological innovation to refine 3D ink production. This method could mark a pivotal advancement in the realm of 3D materials, unlocking numerous prospective applications.

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.

Ionic crosslinking strategies for poly(acrylamide) /alginate hybrid hydrogels

Ionically crosslinked alginate hydrogels have been widely studied for application in tissue engineering. Crosslinking of alginates is routinely done by ionic interaction of the carboxyl groups with multivalent anions such as Ca2+ and Fe3+. In more complex hydrogel designs, such as interpenetrating network hydrogels and double network hydrogels, alginates have been combined with other synthetic polymers to benefit from the advantages of both worlds. The effect of different ions on the properties of single network alginate hydrogels and double network poly(acrylamide)/alginate hydrogels have been studied extensively. However, past reports offer less in terms of comparing different crosslinking methods or different salt precursors. Here, we explore the influence of ionic crosslinking strategies used for crosslinking alginate in double network P(AAm)/Alginate hybrid hydrogels. A comparison is made between different calcium-based crosslinking methods, including a two-step method using CaCl2, a one-step method using CaSO4, and a one-step method using the combination of CaCO3 with glucono-δ-lactone (GDL). Furthermore, the effect of different metal ions is investigated, including Fe3+, Al3+, Ba2+, Sr2+, and Ca2+. Mechanical properties of the resulting gels are analyzed by tensile and compression testing, revealing a strong correlation between preparation protocol, counter-ion identity, and mechanical response.

Liquid-in-liquid printing of 3D and mechanically tunable conductive hydrogels

Conductive hydrogels require tunable mechanical properties, high conductivity and complicated 3D structures for advanced functionality in (bio)applications. Here, we report a straightforward strategy to construct 3D conductive hydrogels by programable printing of aqueous inks rich in poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) inside of oil. In this liquid-in-liquid printing method, assemblies of PEDOT:PSS colloidal particles originating from the aqueous phase and polydimethylsiloxane surfactants from the other form an elastic film at the liquid-liquid interface, allowing trapping of the hydrogel precursor inks in the designed 3D nonequilibrium shapes for subsequent gelation and/or chemical cross-linking. Conductivities up to 301 S m−1 are achieved for a low PEDOT:PSS content of 9 mg mL−1 in two interpenetrating hydrogel networks. The effortless printability enables us to tune the hydrogels’ components and mechanical properties, thus facilitating the use of these conductive hydrogels as electromicrofluidic devices and to customize near-field communication (NFC) implantable biochips in the future.

Bienzymatic Generation of Interpenetrating Polymer Networked Engineered Living Materials with Shape Changing Properties

AbstractThe synthesis of a porous shape‐changing interpenetrating network (IPN) bioink for the fabrication of large‐scale (cm) reversibly thermosensitive structures is described. The poly(N‐isopropylacrylamide) (PNIPAm) IPN is generated in situ within an ionically crosslinked alginate hydrogel at room temperature and under aerobic conditions using a horseradish peroxidase (HRP)/glucose oxidase (GOx) bienzymatic initiation system. Mechanical testing assessment of the IPN hydrogels confirm mechanical reinforcement via covalent single network interdigitation. Furthermore, the thermosensitive bioink can be used to print biohybrid reactors containing genetically engineered phosphotriesterase‐expressing E. coli capable of hydrolyzing toxic organophosphorus compounds. Herein, increasing the bioink pore size using the contractile‐thermosensitive response of the IPN improves the temperature‐dependent theoretical mass‐transfer‐limited enzyme catalyzed reaction rate, providing a plausible route to externally regulated enzymatic catalysis within bioprinted structures.

Tunable, thiol-ene, interpenetrating network hydrogels of norbornene-modified carboxymethyl cellulose and cellulose nanofibrils

Carboxymethyl cellulose modified with norbornene groups (NorCMC) and cellulose nanofibrils (CNFs) produced through mechanical refining without chemical pretreatment formed interpenetrating network hydrogels through a UV-light initiated thiol-ene reaction. The molar ratio of thiols in crosslinkers to norbornene groups off the NorCMC (T:N), total polymer weight percent in the hydrogel, and weight percent of CNFs of the total polymer content of the hydrogels were varied to control hydrogel properties. This method enabled orders of magnitude changes to behavior. Swelling in aqueous environments could be significant (>150 %) without CNFs to minimal (<15 %) with the use of 50 % CNFs. NorCMC and CNF networks interacted synergistically to create hydrogels with compression modulus values spanning 1 to 150 kPa - the values of most biological tissues. T:N and total polymer weight percent could be varied to create hydrogels with different CNF content, but the same compression modulus, targeting 10 and 100 kPa hydrogels and providing a system that can independently vary fibrillar content and bulk modulus. Analysis of the effective crosslinks, thiol-ene network mesh size, and burst release of the polymer indicated synergistic interactions of the NorCMC thiol-ene and CNFs networks. These interactions enhanced modulus and degradation control of the network under physiological conditions.

Cell-Instructive Mineralized Microenvironment Regulates Osteogenesis: A Growing SYMBIOSIS of Cell Biology and Biomaterials Engineering in Bone Tissue Regeneration.

One of the objectives of bone tissue engineering is to produce scaffolds that are biocompatible, osteoinductive, and mechanically equivalent to the natural extracellular matrix of bone in terms of structure and function. Reconstructing the osteoconductive bone microenvironment into a scaffold can attract native mesenchymal stem cells and differentiate them into osteoblasts at the defect site. The symbiotic relationship between cell biology and biomaterial engineering could result in composite polymers containing the necessary signals to recreate tissue- and organ-specific differentiation. In the current work, drawing inspiration from the natural stem cell niche to govern stem cell fate, the cell-instructive hydrogel platforms were constructed by engineering the mineralized microenvironment. This work employed two different hydroxyapatite delivery strategies to create a mineralized microenvironment in an alginate-PEGDA interpenetrating network (IPN) hydrogel. The first approach involved coating of nano-hydroxyapatite (nHAp) on poly(lactide-co-glycolide) microspheres and then encapsulating the coated microspheres in an IPN hydrogel for a sustained release of nHAp, whereas the second approach involved directly loading nHAp into the IPN hydrogel. This study demonstrate that both direct encapsulation and a sustained release approach showed enhanced osteogenesis in target-encapsulated cells; however, direct loading of nHAp into the IPN hydrogel increased the mechanical strength and swelling ratio of the scaffold by 4.6-fold and 1.14-fold, respectively. In addition, the biochemical and molecular studies revealed improved osteoinductive and osteoconductive potential of encapsulated target cells. Being less expensive and simple to perform, this approach could be beneficial in clinical settings.