Dual electro-/pH-responsive nanoparticle/hydrogel system for controlled delivery of anticancer peptide.

An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.

Glyoxal crosslinking of electro-responsive alginate-based hydrogels: Effects on the properties.

To improve the features of alginate-based hydrogels in physiological conditions, Ca2+-crosslinked semi-interpenetrated hydrogels formed by poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid and alginate (PEDOT/Alg) were subjected to a treatment with glyoxal to form a dual ionic/covalent network. The covalent network density was systematically varied by considering different glyoxalization times (tG). The content of Ca2+ was significantly higher for the untreated hydrogel than for the glyoxalized ones, while the properties of the hydrogels were found to largely depend on tG. The porosity and swelling capacity decreased with increasing tG, while the stiffness and electrical conductance retention capacity increased with tG. The potentiodynamic response of the hydrogels notably depended on the amount of conformational restraints introduced by the glyoxal, which is a very short crosslinker. Thus, the re-accommodation of the polymer chains during the cyclic potential scans became more difficult with increasing number of covalent crosslinks. This information was used to improve the performance of untreated PEDOT/Alg as electrochemical sensor of hydrogen peroxide by simply applying a tG of 5 min. Overall, the control of the properties of glyoxalized hydrogels through tG is very advantageous and can be used as an on-demand strategy to improve the performance of such materials depending on the application.

4D Printable Salicylic Acid Photopolymers for Sustained Drug Releasing, Shape Memory, Soft Tissue Scaffolds.

3D printing of pharmaceuticals offers a unique opportunity for long-term, sustained drug release profiles for an array of treatment options. Unfortunately, this approach is often limited by physical compounding or processing limitations. Modification of the active drug into a prodrug compound allows for seamless incorporation with advanced manufacturing methods that open the door to production of complex tissue scaffold drug depots. Here we demonstrate this concept using salicylic acids with varied prodrug structures for control of physical and chemical properties. The role of different salicylic acid derivatives (salicylic acid, bromosalicylic allyl ester, iodosalicylic allyl ester) and linker species (allyl salicylate, allyl 2-(allyloxy)benzoate, allyl 2-(((allyloxy)carbonyl)oxy)benzoate) were investigated using thiol-ene cross-linking in digital light processing (DLP) 3D printing to produce porous prodrug tissue scaffolds containing more than 50% salicylic acid by mass. Salicylic acid photopolymer resins were all found to be highly reactive (solidification within 5 s of irradiation at λ = 405 nm), while the cross-linked solids display tunable thermomechanical behaviors with low glass transition temperatures (Tgs) and elastomeric behaviors, with the carbonate species displaying an elastic modulus matching that of adipose tissue (approximately 65 kPa). Drug release profiles were found to be zero order, sustained release based upon hydrolytic degradation of multilayered scaffolds incorporating fluorescent modeling compounds, with release rates tuned through selection of the linker species. Cytocompatibility in 2D and 3D was further demonstrated for all species compared to polycarbonate controls, as well as salicylic acid-containing composites (physical incorporation), over a 2-week period using murine fibroblasts. The use of drugs as the matrix material for solid prodrug tissue scaffolds opens the door to novel therapeutic strategies, longer sustained release profiles, and even reduced complications for advanced medicine.

Enzymatic Degradation of Polylactic Acid Fibers Supported on a Hydrogel for Sustained Release of Lactate.

The incorporation of exogenous lactate into cardiac tissues is a regenerative strategy that is rapidly gaining attention. In this work, two polymeric platforms were designed to achieve a sustained release of lactate, combining immediate and prolonged release profiles. Both platforms contained electrospun poly(lactic acid) (PLA) fibers and an alginate (Alg) hydrogel. In the first platform, named L/K(x)/Alg-PLA, lactate and proteinase K (x mg of enzyme per 1 g of PLA) were directly loaded into the Alg hydrogel, into which PLA fibers were assembled. In the second platform, L/Alg-K(x)/PLA, fibers were produced by electrospinning a proteinase K:PLA solution and, subsequently, assembled within the lactate-loaded hydrogel. After characterizing the chemical, morphological, and mechanical properties of the systems, as well as their cytotoxicity, the release profiles of the two platforms were determined considering different amounts of proteinase K (x = 5.2, 26, and 52 mg of proteinase K per 1 g of PLA), which is known to exhibit a broad cleavage activity. The profiles obtained using L/Alg-K(x)/PLA platforms with x = 26 and 52 were the closest to the criteria that must be met for cardiac tissue regeneration. Finally, the amount of lactate directly loaded in the Alg hydrogel for immediate release and the amount of protein in the electrospinning solution were adapted to achieve a constant lactate release of around 6 mM per day over 1 or 2 weeks. In the optimized bioplatform, in which 6 mM lactate was loaded in the hydrogel, the amount of fibers was increased by a factor of ×3, the amount of enzyme was adjusted to 40 mg per 1 g of PLA, and a daily lactate release of 5.9 ± 2.7 mM over a period of 11 days was achieved. Accordingly, the engineered device fully satisfied the characteristics and requirements for heart tissue regeneration.

Digital Light Processing-3D Printing of Thermoset Materials with High Biodegradability from Amino Acid-Derived Acrylamide Monomers.

Six acrylamide resins, derived from l-phenylalanine and l-leucine, are designed for application in digital light processing (DLP) printers to obtain biodegradable thermoset polymers. The acrylamide copolymers are prepared under light irradiation at 405 nm and thermal post-curing processes. Low molecular weight poly(ethylene glycol)diacrylate (PEGDA) and N,N-dimethylacrylamide (DMAM), both liquid resins, are used as co-monomers and diluents for the amino acid-derived acrylamide solubilization. The presence of two phenylalanine units and two ester groups in the acrylamide monomer accuses a fast degradation rate in hydrolytic medium in 90 days. The residual products leached in the aqueous media prove to be non-cytotoxic, when 3D-printed samples are cultured with osteoblast cells (MG63), which represents an advantage for the safe disposal of printer waste materials. The scaled-up pieces derived from l-phenylalanine and diethylene glycol, as amino acid-derived acrylamide (named compound C), PEGDA and DMAM, present high dimensional stability after DLP printing of complex structures used as testing samples. Layers of 50 µm of thickness are well cohesive having isotropic behavior, as demonstrated with tensile-strain measurements performed in X-Y-Z (plane) directions. The compound C, which contains phenylalanine amino acid, reveals a promising potential to replace non-biodegradable acrylate polymers used in prototyping systems.

Smart Design of Sensor-Coated Surgical Sutures for Bacterial Infection Monitoring.

Virtually, all implantable medical devices are susceptible to infection. As the main healthcare issue concerning implantable devices is the elevated risk of infection, different strategies based on the coating or functionalization of biomedical devices with antiseptic agents or antibiotics are proposed. In this work, an alternative approach is presented, which consists of the functionalization of implantable medical devices with sensors capable of detecting infection at very early stages through continuous monitoring of the bacteria metabolism. This approach, which is implemented in surgical sutures as a representative case of implantable devices susceptible to bacteria colonization, is expected to minimize the risk of worsening the patient's clinical condition. More specifically, non-absorbable polypropylene/polyethylene (PP/PE) surgical sutures are functionalized with conducting polymers using a combination of low-pressure oxygen plasma, chemical oxidative polymerization, and anodic polymerization, to detect metabolites coming from bacteria respiration. Functionalized suture yarns are used for real-time monitoring of bacteria growth, demonstrating the potential of this strategy to fight against infections.

Multifunctional conductive hyaluronic acid hydrogels for wound care and skin regeneration.

Although the main function of skin is to act as a protective barrier against external factors, it is indeed an extremely vulnerable tissue. Skincare, regardless of the wound type, requires effective treatments to prevent bacterial infection and local inflammation. The complex biological roles displayed by hyaluronic acid (HA) during the wound healing process have made this multifaceted polysaccharide an alternative biomaterial to prepare wound dressings. Therefore, herein, we present the most advanced research undertaken to engineer conductive and interactive hydrogels based on HA as wound dressings that enhance skin tissue regeneration either through electrical stimulation (ES) or by displaying multifunctional performance. First, we briefly introduce to the reader the effect of ES on promoting wound healing and why HA has become a vogue as a wound healing agent. Then, a selection of systems, chosen according to their multifunctional relevance, is presented. Special care has been taken to highlight those recently reported works (mainly from the last 3 years) with enhanced scalability and biomimicry. By doing that, we have turned a critical eye on the field considering what major challenges must be overcome for these systems to have real commercial, clinical, or other translational impact.

Immediate-sustained lactate release using alginate hydrogel assembled to proteinase K/polymer electrospun fibers.

This work proposes a microfibers-hydrogel assembled composite as delivery vehicle able to combine into a single system both burst and prolonged release of lactate. The prolonged release of lactate has been achieved by electrospinning a mixture of polylactic acid and proteinase K (26.0 mg of proteinase K and 0.99 g of PLA dissolved in 6 mL of 2:1 chloroform:acetone in the optimal case), which is a protease that catalyzes the degradation of polylactic acid into lactate. The degradation of microfibers into lactate reflects that proteinase K preserves its enzymatic activity even after the electrospinning process because of the mild operational conditions used. Besides, burst release is obtained from the lactate-loaded alginate hydrogel. The successful assembly between the lactate-loaded hydrogel and the polylactic acid/proteinase K fibers has been favored by applying a low-pressure (0.3 mbar at 300 W) oxygen plasma treatment, which transforms hydrophobic fibers into hydrophilic while the enzymatic activity is still maintained. The composite displays both fast (< 24 h) and sustained (> 10 days) lactate release, and allows the modulation of the release by adjusting either the amount of loaded lactate or the amount of active enzyme.

Electroresponsive and pH-Sensitive Hydrogel as Carrier for Controlled Chloramphenicol Release.

Multiresponsive hydrogels, which are smart soft materials that respond to more than one external stimulus, have emerged as powerful tools for biomedical applications, such as drug delivery. Within this context and with the aim of eliminating the systematic administration of antibiotics, special attention is being paid to the development of systems for controlled delivery of antibiotic for topical treatment of bacterial infections. In this work, an electro-chemo responsive hydrogel able to release chloramphenicol (CAM), a broad spectrum antibiotic also used for anticancer therapy, is proposed. This has been prepared by grafting poly(acrylic acid) (PAA) to sodium alginate (Alg) and in situ encapsulation of poly(3,4-ethylenedioxythiophene) nanoparticles loaded with CAM (PEDOT/CAM NPs), which were obtained by emulsion polymerization. Although the response to electrical stimuli of PEDOT was the main control for the release of CAM from PEDOT/CAM NPs, the release by passive diffusion had a relatively important contribution. Conversely, the passive release of antibiotic from the whole engineered hydrogel system, Alg-g-PAA/PEDOT/CAM, was negligible, whereas significant release was achieved under electrostimulation in an acid environment. Bacterial tests and assays with cancer cells demonstrated that the biological activity of CAM remained after release by electrical stimulation. Notably, the successful dual-response of the developed hydrogel to electrical stimuli and pH changes evidence the great prospect of this smart material in the biomedical field, as a tool to fight against bacterial infections and to provide local cancer treatment.

Beyond biology: alternative uses of cantilever-based technologies.

Micromechanical cantilever sensors are attracting a lot of attention because of the need for characterizing, detecting, and monitoring chemical and physical properties, as well as compounds at the nanoscale. The fields of application of micro-cantilever sensors span from biological and point-of-care, to military or industrial sectors. The purpose of this work focuses on thermal and mechanical characterization, environmental monitoring, and chemical detection, in order to provide a technical review of the most recent technical advances and applications, as well as the future prospective of micro-cantilever sensor research.

Preparation and Characterization of Functionalized Surgical Meshes for Early Detection of Bacterial Infections.

Isotactic polypropylene (i-PP) nonabsorbable surgical meshes are modified by incorporating a conducting polymer (CP) layer to detect the adhesion and growth of bacteria by sensing the oxidation of nicotinamide adenine dinucleotide (NADH), a metabolite produced by the respiration reactions of such microorganisms, to NAD+. A three-step process is used for such incorporation: (1) treat pristine meshes with low-pressure O2 plasma; (2) functionalize the surface with CP nanoparticles; and (3) coat with a homogeneous layer of electropolymerized CP using the nanoparticles introduced in (2) as polymerization nuclei. The modified meshes are stable and easy to handle and also show good electrochemical response. The detection by cyclic voltammetry of NADH within the interval of concentrations reported for bacterial cultures is demonstrated for the two modified meshes. Furthermore, Staphylococcus aureus and both biofilm-positive (B+) and biofilm-negative (B-) Escherichia coli cultures are used to prove real-time monitoring of NADH coming from aerobic respiration reactions. The proposed strategy, which offers a simple and innovative process for incorporating a sensor for the electrochemical detection of bacteria metabolism to currently existing surgical meshes, holds considerable promise for the future development of a new generation of smart biomedical devices to fight against post-operative bacterial infections.

Dendritic Self-assembled Structures from Therapeutic Charged Pentapeptides.

CRENKA [Cys-Arg-(NMe)Glu-Lys-Ala, where (NMe)Glu refers to N-methyl-Glu], an anti-cancer pentapeptide that induces prostate tumor necrosis and significant reduction in tumor growth, was engineered to increase the resistance to endogenous proteases of its parent peptide, CREKA (Cys-Arg-Glu-Lys-Ala). Considering their high tendency to aggregate, the self-assembly of CRENKA and CREKA into well-defined and ordered structures has been examined as a function of peptide concentration and pH. Spectroscopic studies and atomistic molecular dynamics simulations reveal significant differences between the secondary structures of CREKA and CRENKA. Thus, the restrictions imposed by the (NMe)Glu residue reduce the conformational variability of CRENKA with respect to CREKA, which significantly affects the formation of well-defined and ordered self-assembly morphologies. Aggregates with poorly defined morphology are obtained from solutions with low and moderate CREKA concentrations at pH 4, whereas well-defined dendritic microstructures with fractal geometry are obtained from CRENKA solutions with similar peptide concentrations at pH 4 and 7. The formation of dendritic structures is proposed to follow a two-step mechanism: (1) pseudo-spherical particles are pre-nucleated through a diffusion-limited aggregation process, pre-defining the dendritic geometry, and (2) such pre-nucleated structures coalesce by incorporating conformationally restrained CRENKA molecules from the solution to their surfaces, forming a continuous dendritic structure. Instead, no regular assembly is obtained from solutions with high peptide concentrations, as their dynamics is dominated by strong repulsive peptide-peptide electrostatic interactions, and from solutions at pH 10, in which the total peptide charge is zero. Overall, results demonstrate that dendritic structures are only obtained when the molecular charge of CRENKA, which is controlled through the pH, favors kinetics over thermodynamics during the self-assembly process.

Self-assembly pathways in a triphenylalanine peptide capped with aromatic groups.

Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphenylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N- and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylmethyloxycarbonyl and benzyl ester end-capping groups at the N- and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in ß-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm ß-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the medium on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addition, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of π-π stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which determines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.

Using Stereochemistry to Control Mechanical Properties in Thiol-Yne Click-Hydrogels.

The stereochemistry of polymers has a profound impact on their mechanical properties. While this has been observed in thermoplastics, studies on how stereochemistry affects the bulk properties of swollen networks, such as hydrogels, are limited. Typically, changing the stiffness of a hydrogel is achieved at the cost of changing another parameter, that in turn affects the physical properties of the material and ultimately influences the cellular response. Herein, we report that by manipulating the stereochemistry of a double bond, formed in situ during gelation, materials with diverse mechanical properties but comparable physical properties can be obtained. Click-hydrogels that possess a high % trans content are stiffer than their high % cis analogues by almost a factor of 3. Human mesenchymal stem cells acted as a substrate stiffness cell reporter demonstrating the potential of these platforms to study mechanotransduction without the influence of other external factors.

Electrical and Capacitive Response of Hydrogel Solid-Like Electrolytes for Supercapacitors.

Flexible hydrogels are attracting significant interest as solid-like electrolytes for energy storage devices, especially for supercapacitors, because of their lightweight and anti-deformation features. Here, we present a comparative study of four ionic conductive hydrogels derived from biopolymers and doped with 0.1 M NaCl. More specifically, such hydrogels are constituted by κ-carrageenan (κC), carboxymethyl cellulose (CMC), poly-γ-glutamic acid (PGGA) or a phenylalanine-containing polyesteramide (PEA). After examining the morphology and the swelling ratio of the four hydrogels, which varies between 483% and 2356%, their electrical and capacitive behaviors were examined using electrochemical impedance spectroscopy. Measurements were conducted on devices where a hydrogel film was sandwiched between two identical poly(3,4-ethylenedioxythiophene) electrodes. The bulk conductivity of the prepared doped hydrogels is 76, 48, 36 and 34 mS/cm for PEA, PGGA, κC and CMC, respectively. Overall, the polyesteramide hydrogel exhibits the most adequate properties (i.e., low electrical resistance and high capacitance) to be used as semi-solid electrolyte for supercapacitors, which has been attributed to its distinctive structure based on the homogeneous and abundant distribution of both micro- and nanopores. Indeed, the morphology of the polyestermide hydrogel reduces the hydrogel resistance, enhances the transport of ions, and results in a better interfacial contact between the electrodes and solid electrolyte. The correlation between the supercapacitor performance and the hydrogel porous morphology is presented as an important design feature for the next generation of light and flexible energy storage devices for wearable electronics.

Plasma-Functionalized Isotactic Polypropylene Assembled with Conducting Polymers for Bacterial Quantification by NADH Sensing.

Rapid detection of bacterial presence on implantable medical devices is essential to prevent biofilm formation, which consists of densely packed bacteria colonies able to withstand antibiotic-mediated killing. In this work, a smart approach is presented to integrate electrochemical sensors for detecting bacterial infections in biomedical implants made of isotactic polypropylene (i-PP) using chemical assembly. The electrochemical detection is based on the capacity of conducting polymers (CPs) to detect extracellular nicotinamide adenine dinucleotide (NADH) released from cellular respiration of bacteria, which allows distinguishing prokaryotic from eukaryotic cells. Oxygen plasma-functionalized free-standing i-PP, coated with a layer (≈1.1 µm in thickness) of CP nanoparticles obtained by oxidative polymerization, is used as working electrode for the anodic polymerization of a second CP layer (≈8.2 µm in thickness), which provides very high electrochemical activity and stability. The resulting layered material, i-PPf /CP2 , detects the electro-oxidation of NADH in physiological media with a sensitivity 417 µA cm-2 and a detection limit up to 0.14 × 10-3 m, which is below the concentration of extracellular NADH found for bacterial cultures of biofilm-positive and biofilm-negative strains.

Customized Fading Scaffolds: Strong Polyorthoester Networks via Thiol-Ene Cross-linking for Cytocompatible Surface-Eroding Materials in 3D Printing.

Polyorthoesters are a highly desirable class of cytocompatible materials that are able to rapidly surface-erode. Despite their promise, their mechanical weakness and complex synthesis have limited their processability and application in advanced technologies. Herein, we report a readily accessible family of cross-linked poly(orthoester-thioether) (POETE) materials that are suitable for processing via photopolymerization. Polymer networks are accessed through bifunctional orthoester precursors using simple thiol-ene addition chemistry. The mobility of the polymer chains and the cross-linking density within the polymer structure can be tuned through the choice of the monomer, which in turn presents customizable thermal and mechanical properties in the resulting materials. The photopolymerizability of these POETE materials also allows for processing via additive manufacturing, which is demonstrated on a commercial 3D printer. Post-processing conditions and architecture are crucial to material degradability and are exploited for programmed bulk-release applications with degradation rate and release time linearly dependent on the specimen dimensions, such as strand or shell thickness. Analogous to acid-releasing polylactide materials, degradation products of the POETE materials show cytocompatibility below a certain concentration/acidity threshold. This research highlights the simplicity, versatility, and applicability of POETE networks as cytocompatible, surface-eroding materials that can be processed by additive manufacturing for advanced applications.

Using Stereochemistry to Control Mechanical Properties in Thiol-Yne Click-Hydrogels.

The stereochemistry of polymers has a profound impact on their mechanical properties. While this has been observed in thermoplastics, studies on how stereochemistry affects the bulk properties of swollen networks, such as hydrogels, are limited. Typically, changing the stiffness of a hydrogel is achieved at the cost of changing another parameter, that in turn affects the physical properties of the material and ultimately influences the cellular response. Herein, we report that by manipulating the stereochemistry of a double bond, formed in situ during gelation, materials with diverse mechanical properties but comparable physical properties can be obtained. Click-hydrogels that possess a high % trans content are stiffer than their high % cis analogues by almost a factor of 3. Human mesenchymal stem cells acted as a substrate stiffness cell reporter demonstrating the potential of these platforms to study mechanotransduction without the influence of other external factors.

Modular Functionalization of Laminarin to Create Value-Added Naturally Derived Macromolecules.

With society's growing awareness of climate change, novel renewable and naturally sourced materials have received increasing attention as substitutes for petroleum-based products. Laminarin (LAM-OH) is a highly abundant, nontoxic, degradable polysaccharide found in marine organisms and hence is a promising sustainable polymeric candidate. This work reports on a simple, environmentally friendly, and customizable functionalization strategy for producing a toolbox of LAM-OH derivatives under mild conditions. Herein, natural-origin macromolecules exhibiting specific chemical moieties, namely, allyl, amine, carboxylic acid, thiol, aldehyde, and catechol, were prepared and chemically characterized. Furthermore, the obtained polymers were processed into cytocompatible hydrogels, obtained by employing distinct cross-linking mechanisms, to assess their potential for biomedical purposes. The application scope of such polymers could be extended to fields such as catalysis, cosmetics, life sciences, and food packaging, which can also benefit from having sustainable, nontoxic, and degradable materials. Moreover, it is anticipated that the methodology employed to create this library of new natural-based products could be adapted to modify other polysaccharides and biopolymers in general.

Advanced Functional Hydrogel Biomaterials Based on Dynamic B-O Bonds and Polysaccharide Building Blocks.

Dynamic covalent chemistry applied to polymers has attracted significant attention over the past decade. Within this area, this review highlights the recent research on polysaccharide-based hydrogels cross-linked by boronic acid moieties, illustrating its versatility and relevance in biomaterials science to design self-healing, multiple stimuli-responsive, and adaptive biointerfaces and advanced functional devices.