Mussel‐Inspired Hydrogels for Self‐Adhesive Bioelectronics

Wearable and implantable bioelectronics are receiving a great deal of attention because they offer huge promise in personalized healthcare. Currently available bioelectronics generally rely on external aids to form an attachment to the human body, which leads to unstable performance in practical applications. Self‐adhesive bioelectronics are highly desirable for ameliorating these concerns by offering reliable and conformal contact with tissue, and stability and fidelity in the signal detection. However, achieving adequate and long‐term self‐adhesion to soft and wet biological tissues has been a daunting challenge. Recently, mussel‐inspired hydrogels have emerged as promising candidates for the design of self‐adhesive bioelectronics. In addition to self‐adhesiveness, the mussel‐inspired chemistry offers a unique pathway for integrating multiple functional properties to all‐in‐one bioelectronic devices, which have great implications for healthcare applications. In this report, the recent progress in the area of mussel‐inspired self‐adhesive bioelectronics is highlighted by specifically discussing: 1) adhesion mechanism of mussels, 2) mussel‐inspired hydrogels with long‐term and repeatable adhesion, 3) the recent advance in development of hydrogel bioelectronics by reconciling self‐adhesiveness and additional properties including conductivity, toughness, transparency, self‐healing, antibacterial properties, and tolerance to extreme environment, and 4) the challenges and prospects for the future design of the mussel‐inspired self‐adhesive bioelectronics.     

Graphene Oxide‐Templated Conductive and Redox‐Active Nanosheets Incorporated Hydrogels for Adhesive Bioelectronics

2D conductive nanosheets are central to electronic applications because of their large surface areas and excellent electronic properties. However, tuning the multifunctions and hydrophilicity of conductive nanosheets are still challenging. Herein, a green strategy is developed for fabricating conductive, redox‐active, water‐soluble nanosheets via the self‐assembly of poly(3,4‐ethylenedioxythiophene) (PEDOT) on the polydopamine‐reduced and sulfonated graphene oxide (PSGO) template. The conductivity and hydrophilicity of nanosheets are highly improved by PSGO. The nanosheets are redox active due to the abundant catechol groups and can be used as versatile nanofillers in developing conductive and adhesive hydrogels. The nanosheets create a mussel‐inspired redox environment inside the hydrogel networks and endow the hydrogel with long‐term and repeatable adhesiveness. This hydrogel is biocompatible and can be implanted for biosignals detection in vivo. This mussel‐inspired strategy for assembling 2D nanosheets can be adapted for producing diverse multifunctional nanomaterials, with various potential applications in bioelectronics.     

A Biomimetic Mussel‐Inspired ε‐Poly‐l‐lysine Hydrogel with Robust Tissue‐Anchor and Anti‐Infection Capacity

In situ hydrogels have attracted considerable attention in tissue engineering because of their minimal invasiveness and ability to match the irregular tissue defects. However, hydrous physiological environments and the high level of moisture in hydrogels severely hamper binding to the target tissue and easily cause wound infection, thereby limiting the effectiveness in wound care management. Thus, forming an intimate assembly of the hydrogel to the tissue and preventing wound infecting still remains a significant challenge. In this study, inspired by mussel adhesive protein, a biomimetic dopamine‐modified ε‐poly‐l ‐lysine‐polyethylene glycol‐based hydrogel (PPD hydrogel) wound dressing is developed in situ using horseradish peroxidase cross‐linking. The biomimetic catechol–Lys residue distribution in PPD polymer provides a catechol–Lys cooperation effect, which endows the PPD hydrogels with superior wet tissue adhesion properties. It is demonstrated that the PPD hydrogel can facilely and intimately integrate with biological tissue and exhibits superior capacity of in vivo hemostatic and accelerated wound repair. In addition, the hydrogels exhibit outstanding anti‐infection property because of the inherent antibacterial ability of ε‐poly‐l ‐lysine. These findings shed new light on the development of mussel‐inspired tissue‐anchored and antibacterial hydrogel materials serving as wound dressings.     

Alginate‐Boronic Acid: pH‐Triggered Bioinspired Glue for Hydrogel Assembly

The development of bioadhesives has become an emerging research field for tissue sealants, wound dressings, and hemostatic agents. However, assembling hydrogels using bioadhesive‐mediated attachment remains a challenging task. Significantly high water content (>90%) in hydrogels compared to that of biological tissues is the main cause of failure. Considering that hydrogels are primary testing scaffolds mimicking in vivo environments, developing strategies to assemble hydrogels that exhibit diverse properties is important. Self‐healing gels have been reported, but such gels often lack biocompatibility, and two gel pieces should be identical in chemistry for assembly, thus not allowing co‐existence of diverse biological environments. Herein, a mussel‐mimetic cis‐diol‐based adhesive, alginate‐boronic acid, that exhibits pH‐responsive curing from a viscoelastic solution to soft gels is developed. Associated mechanisms are that 1) polymeric diffusion occurs at interfaces utilizing intrinsic high water content; 2) the conjugated cis‐diols strongly interact/entangle with hydrogel chains; 3) curing processes begin by a slight increase in pH, resulting in robust attachment of diverse types of hydrogel building blocks for assembly. The findings obtained with alginate‐boronic acid glues suggest a rational design principle to attach diverse hydrogel building blocks to provide platforms mimicking in vivo environments.     

A Highly Elastic and Rapidly Crosslinkable Elastin‐Like Polypeptide‐Based Hydrogel for Biomedical Applications

Elastin‐like polypeptides (ELPs) are promising for biomedical applications due to their unique thermoresponsive and elastic properties. ELP‐based hydrogels have been produced through chemical and enzymatic crosslinking or photocrosslinking of modified ELPs. Herein, a photocrosslinked ELP gel using only canonical amino acids is presented. The inclusion of thiols from a pair of cysteine residues in the ELP sequence allows disulfide bond formation upon exposure to UV light, leading to the formation of a highly elastic hydrogel. The physical properties of the resulting hydrogel such as mechanical properties and swelling behavior can be easily tuned by controlling ELP concentrations. The biocompatibility of the engineered ELP hydrogels is shown in vitro as well as corroborated in vivo with subcutaneous implantation of hydrogels in rats. ELP constructs demonstrate long‐term structural stability in vivo, and early and progressive host integration with no immune response, suggesting their potential for supporting wound repair. Ultimately, functionalized ELPs demonstrate the ability to function as an in vivo hemostatic material over bleeding wounds.     

Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability,Fast Self‐Healing,Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

Developing physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe³⁺ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.     

Tissue Adhesive Catechol‐Modified Hyaluronic Acid Hydrogel for Effective,Minimally Invasive Cell Therapy

Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue‐adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA‐catechol (HA‐CA) hydrogel via oxidative crosslinking. HA‐CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose‐derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA‐CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA‐CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA‐CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue‐adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.     

Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.     

Self‐Hydrophobization in a Dynamic Hydrogel for Creating Nonspecific Repeatable Underwater Adhesion

Adhesive hydrogels are widely applied for biological and medical purposes; however, they are generally unable to adhere to tissues under wet/underwater conditions. Herein, described is a class of novel dynamic hydrogels that shows repeatable and long‐term stable underwater adhesion to various substrates including wet biological tissues. The hydrogels have Fe³⁺‐induced hydrophobic surfaces, which are dynamic and can undergo a self‐hydrophobization process to achieve strong underwater adhesion to a diverse range of dried/wet substrates without the need for additional processes or reagents. It is also demonstrated that the hydrogels can directly adhere to biological tissues in the presence of under sweat, blood, or body fluid exposure, and that the adhesion is compatible with in vivo dynamic movements. This study provides a novel strategy for fabricating underwater adhesive hydrogels for many applications, such as soft robots, wearable devices, tissue adhesives, and wound dressings.     

Nanoporous Substrate‐Infiltrated Hydrogels: a Bioinspired Regenerable Surface for High Load Bearing and Tunable Friction

Nature has successfully combined soft matter and hydration lubrication to achieve ultralow friction even at relatively high contact pressure (e.g., articular cartilage). Inspired by this, hydrogels are used to mimic natural aqueous lubricating systems. However, hydrogels usually cannot bear high load because of solvation in water environments and are, therefore, not adopted in real applications. Here, a novel composite surface of ordered hydrogel nanofiber arrays confined in anodic aluminum oxide (AAO) nanoporous template based on a soft/hard combination strategy is developed. The synergy between the soft hydrogel fibers, which provide excellent aqueous lubrication, and the hard phase AAO, which gives high load bearing capacity, is shown to be capable of attaining very low coeffcient of friction (<0.01) under heavy load (contact pressures ≈2 MPa). Interestingly, the composite synthetic material is very stable, cannot be peeled off during sliding, and exhibits desirable regenerative (self‐healing) properties, which can assure long‐term resistance to wear. Moreover, the crosslinked polymethylacrylic acid hydrogels are shown to be able to promptly switch between high friction (>0.3) and superlubrication (≈10^?3) when their state is changed from contracted to swollen by means of acidic and basic actuation. The mechanisms governing ultralow and tunable friction are theoretically explained via an in‐depth study of the chemomechanical interactions responsible for the behavior of these substrate‐infiltrated hydrogels. These findings open a promising route for the design of ultra‐slippery and smart surface/interface materials.     

Stimuli‐Responsive Donor–Acceptor and DNA‐Crosslinked Hydrogels: Application as Shape‐Memory and Self‐Healing Materials

Carboxymethyl cellulose (CMC) chains are functionalized with self‐complementary nucleic acid tethers and electron donor or electron acceptor functionalities. The polymer chains crosslinked by the self‐complementary duplex nucleic acids and the donor–acceptor complexes as bridging units, yield a stiff stimuli‐responsive hydrogel. Upon the oxidation of the electron donor units, the donor–acceptor bridging units are separated, leading to a hydrogel of lower stiffness. By the cyclic oxidation and reduction of the donor units, the hydrogel is reversibly transformed across low and high stiffness states. The controlled stiffness properties of the hydrogel are used to develop shape‐memory hydrogels. In addition, CMC hydrogels crosslinked by donor–acceptor complexes and K⁺‐stabilized G‐quadruplexes reveal stimuli‐responsive properties that exhibit dually triggered stiffness functions. While the hydrogel bridged by the two crosslinking motifs reveals high stiffness, the redox‐stimulated separation of the donor–acceptor complexes or the crown‐ether‐stimulated separation of the G‐quadruplex bridges yields two alternative hydrogels exhibiting low stiffness states. The control over the stiffness properties of the dually triggered hydrogel is used to develop shape‐memory hydrogels, where the donor–acceptor units or G‐quadruplex bridges act as “memories”, and to develop triggered self‐healing process of the hydrogel.     

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.     

Covalently Adaptable Elastin‐Like Protein–Hyaluronic Acid (ELP–HA) Hybrid Hydrogels with Secondary Thermoresponsive Crosslinking for Injectable Stem Cell Delivery

Shear‐thinning, self‐healing hydrogels are promising vehicles for therapeutic cargo delivery due to their ability to be injected using minimally invasive surgical procedures. An injectable hydrogel using a novel combination of dynamic covalent crosslinking with thermoresponsive engineered proteins is presented. Ex situ at room temperature, rapid gelation occurs through dynamic covalent hydrazone bonds by simply mixing two components: hydrazine‐modified elastin‐like protein (ELP) and aldehyde‐modified hyaluronic acid. This hydrogel provides significant mechanical protection to encapsulated human mesenchymal stem cells during syringe needle injection and rapidly recovers after injection to retain the cells homogeneously within a 3D environment. In situ, the ELP undergoes a thermal phase transition, as confirmed by coherent anti‐Stokes Raman scattering microscopy observation of dense ELP thermal aggregates. The formation of the secondary network reinforces the hydrogel and results in a tenfold slower erosion rate compared to a control hydrogel without secondary thermal crosslinking. This improved structural integrity enables cell culture for three weeks postinjection, and encapsulated cells maintain their ability to differentiate into multiple lineages, including chondrogenic, adipogenic, and osteogenic cell types. Together, these data demonstrate the promising potential of ELP–HA hydrogels for injectable stem cell transplantation and tissue regeneration.     

Supramolecular β‐Sheet Suckerin–Based Underwater Adhesives

Nature has evolved several molecular strategies to ensure adhesion in aqueous environments, where artificial adhesives typically fail. One recently‐unveiled molecular design for wet‐resistant adhesion is the cohesive cross‐β structure characteristic of amyloids, complementing the well‐established surface‐binding strategy of mussel adhesive proteins based on 3,4‐l ‐dihydroxyphenylalanine (Dopa). Structural proteins that self‐assemble into cross β‐sheet networks are the suckerins discovered in the sucker ring teeth of squids. Here, light is shed on the wet adhesion of cross‐β motifs by producing recombinant suckerin‐12, naturally lacking Dopa, and investigating its wet adhesion properties. Surprisingly, the adhesion forces measured on mica reach 70 mN m^?1, exceeding those measured for all mussel adhesive proteins to date. The pressure‐sensitive adhesion of artificial suckerins is largely governed by their cross‐β motif, as evidenced using control experiments with disrupted cross‐β domains that result in complete loss of adhesion. Dopa is also incorporated in suckerin‐12 using a residue‐specific incorporation strategy that replaces tyrosine with Dopa during expression in Escherichia coli. Although the replacement does not increase the long‐term adhesion, it contributes to the initial rapid contact and enhances the adsorption onto model oxide substrates. The findings suggest that suckerins with supramolecular cross‐β motifs are promising biopolymers for wet‐resistant adhesion.     

Bioinspired Double‐Dynamic‐Bond Crosslinked Bioadhesive Enables Post‐Wound Closure Care

Most existing bioadhesives, even those showing superiority in wound closure effectiveness, do not assist in the post‐wound closure process. A bioinspired, in situ formed, double‐dynamic‐bond crosslinked hydrogel bioadhesive that is capable of efficiently closing open wounds and enabling post‐wound closure care is reported. Catechol‐modified ε‐poly‐l ‐lysine and oxidized dextran are employed as natural polymer backbones and they are in situ crosslinked using Schiff's base dynamic bond and catechol? Fe coordinate dynamic bond through a process inspired by that used to cure marine mussel glue, forming a hydrogel bioadhesive. The unique double‐dynamic‐bond crosslinked structure endows the bioadhesive with higher mechanical and adhesive strength while retaining quick dissociation and good self‐healing capacities. Accordingly, the bioadhesive can exhibit multiple desirable functions, such as dissolution on demand, repeatable adhesiveness, adhesive and mechanical strength sufficient for wound closure, injectability, and good biocompatibility (DREAMING). After efficiently closing skin incisions, the bioadhesive can be facilely removed or repeatedly close the reopened wounds, thus enabling post‐wound closure care. On the basis of favorable functions in wound closure and the ability to enable post‐wound closure care, the bioadhesive demonstrates great potential in dealing with skin wounds.     

Redox‐Active Iron‐Citrate Complex Regulated Robust Coating‐Free Hydrogel Microfiber Net with High Environmental Tolerance and Sensitivity

Stretchable hydrogel microfibers as a novel type of ionic conductors are promising in gaining skin‐like sensing applications in more diverse scenarios. However, it remains a great challenge to fabricate coating‐free but water‐retaining conductive hydrogel microfibers with a good balance of spinnability and mechanical strength. Here the old yet significant redox chemistry of Fe‐citrate complex is employed to solve this issue in the continuous draw‐spinning process of poly(acrylamide‐co‐sodium acrylate) hydrogel microfibers and microfiber nets from a water/glycerol solution. The resultant microfibers are ionically conductive, highly stretchable, and uniform with tunable diameters. Furthermore, the presence of redox‐reversible Fe‐citrate complex and glycerol endows the fibers with good anti‐freezing, water‐retaining, and environmentally intelligent properties. Humidity and UV light can finely mediate the stiffness of hydrogel microfibers; conversely, the ionic conductance of microfibers is also responsive to light, humidity, and strain, which enables the highly sensitive perception of environmental changes. The present draw‐spinning strategy provides more possibilities for coating‐free conductive hydrogel microfibers with a variety of responsive and sensing applications.     

A Safe Polyzwitterionic Hydrogel Electrolyte for Long‐Life Quasi‐Solid State Zinc Metal Batteries

Aqueous zinc metal batteries are safe, economic, and environmentally friendly. However, the dendrite growth and inevitable corrosion issues under aqueous condition greatly restrict the development of long cycling life zinc metal batteries. To achieve the long‐term reversible zinc deposition/dissolution, a polyzwitterionic hydrogel electrolyte (PZHE) is constructed with record high room temperature ionic conductivity of 32.0 mS cm^?1 and Zn²⁺ transference number of 0.656. The abundant hydrophilic and charged groups in the zwitterionic polymer can well immobilize water molecules in the polymer skeleton and reduce side reactions. The charged groups of the zwitterionic polymer can also homogenize the ion distribution and achieve uniform zinc deposition. Long cycling life of over 3500 h is achieved for the symmetric batteries with PZHE. Full cells with VS₂ and MnO₂ cathodes are also demonstrated to exhibit excellent cycling stability. With combined advantages of physical and chemical crosslinking gels, the PZHE enabled flexible quasi‐solid state zinc metal batteries with excellent processability, self‐healing property and safety, can operate even under various extreme conditions such as cutting, soaking, hammering, washing, burning, and freezing. It is believed that the PZHE can provide a promising opportunity and pave the way for other long‐life aqueous batteries.     

Wet‐Responsive,Reconfigurable, and Biocompatible Hydrogel Adhesive Films for Transfer Printing of Nanomembranes

This study presents a wet‐responsive and biocompatible smart hydrogel adhesive that exhibits switchable and controllable adhesions on demand for the simple and efficient transfer printing of nanomembranes. The prepared hydrogel adhesives show adhesion strength as high as ≈191 kPa with the aid of nano‐ or microstructure arrays on the surface in the dry state. When in contact with water, the nano/microscopic and macroscopic shape reconfigurations of the hydrogel adhesive occur, which turns off the adhesion (≈0.30 kPa) with an extremely high adhesion switching ratio (>640). The superior adhesion behaviors of the hydrogels are maintained over repeating cycles of hydration and dehydration, indicating their ability to be used repeatedly. The adhesives are made of a biocompatible hydrogel and their adhesion on/off can be controlled with water, making the adhesives compatible with various materials and surfaces, including biological substrates. Based on these smart adhesion capabilities, diverse metallic and semiconducting nanomembranes can be transferred from donor substrates to either rigid or flexible surfaces including biological tissues in a reproducible and robust fashion. Transfer printing of a nanoscale crack sensor onto a bovine eye further demonstrates the potential of the reconfigurable hydrogel adhesive for use as a stimuli‐responsive, smart, and versatile functional adhesive for nanotransfer printing.     

An Injectable Supramolecular Polymer Nanocomposite Hydrogel for Prevention of Breast Cancer Recurrence with Theranostic and Mammoplastic Functions

The high locoregional breast cancer recurrence rate poses a significant risk for patients' survival. Injecting theranostic drugs‐laden soft tissue‐like hydrogels into the resected breast cavity is a promising strategy to achieve both precisely local therapy of breast cancer and reconstructive mammoplasty. In this work, a robust injectable thermoresponsive supramolecular poly(N‐acryloyl glycinamide‐co‐acrylamide) (PNAm) hydrogel bearing polydopamine (PDA) coated‐gold nanoparticles (AuNPs) and doxorubicin (DOX) is fabricated. The supramolecular polymer nanocomposite (SPN) hydrogels exhibit an excellent photothermal effect arising from PDA‐AuNPs that are tightly fixed to the hydrogel matrix via PDA and amide moieties in the network, built‐in near infrared (NIR) light‐triggered gel–sol transition as well as tunable drug delivery. The PNAm‐PDAAu‐DOX sol driven by prior heating is injected into the cavity of resected cancerous breasts of rats where gelation occurred rapidly while the temperature decreased to body temperature, thereby finely serving as a breast filler. During 4 week of implantation, interval NIR light irradiation can mediate photothermal effect and concertedly controllable DOX release, thus collectively preventing the recurrence of breast cancer. Remarkably, this stable remoldable SPN hydrogel facilitates the breast reconstruction and can be tracked by computed tomography (CT) imaging owing to the intrinsic X‐ray attenuation property of the loaded AuNPs.     

Time Controlled Protein Release from Layer‐by‐Layer Assembled Multilayer Functionalized Agarose Hydrogels

Axons of the adult central nervous system exhibit an extremely limited ability to regenerate after spinal cord injury. Experimentally generated patterns of axon growth are typically disorganized and randomly oriented. Support of linear axonal growth into spinal cord lesion sites has been demonstrated using arrays of uniaxial channels, templated with agarose hydrogel, and containing genetically engineered cells that secrete brain‐derived neurotrophic factor (BDNF). However, immobilizing neurotrophic factors secreting cells within a scaffold is relatively cumbersome, and alternative strategies are needed to provide sustained release of BDNF from templated agarose scaffolds. Existing methods of loading the drug or protein into hydrogels cannot provide sustained release from templated agarose hydrogels. Alternatively, here it is shown that pH‐responsive H‐bonded poly(ethylene glycol)(PEG)/poly(acrylic acid)(PAA)/protein hybrid layer‐by‐layer (LbL) thin films, when prepared over agarose, provided sustained release of protein under physiological conditions for more than four weeks. Lysozyme, a protein similar in size and isoelectric point to BDNF, is released from the multilayers on the agarose and is biologically active during the earlier time points, with decreasing activity at later time points. This is the first demonstration of month‐long sustained protein release from an agarose hydrogel, whereby the drug/protein is loaded separately from the agarose hydrogel fabrication process.