Dual Hydrogel Research Articles

Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin

Regeneration of injured articular cartilage is limited by low early-stage recruitment of stem cells and insufficient chondrogenic differentiation. Hydrogels are widely used to repair cartilage because they have excellent mechanical and biological properties. In this study, a dual drug-loaded thermosensitive hydroxypropyl chitin hydrogel (HPCH) system was prepared to release stromal-derived factor-1α-like polypeptides (SDFP) and kartogenin (KGN) for stem-cell recruitment and chondrogenic differentiation. The hydrogel had a network structure that promoted cell growth and nutrient exchange. Moreover, it was temperature sensitive and suitable for filling irregular defects. The system showed good biocompatibility in vitro and promoted stem-cell recruitment and chondrogenic differentiation. Furthermore, it reduced chondrocyte catabolism under inflammatory conditions. Animal experiments demonstrated that the dual-drug hydrogel systems can promote the regeneration of articular cartilage in rats. This study confirmed that an HPCH system loaded with KGN and SDFP could effectively repair articular cartilage defects and represents a viable treatment strategy.

Dual thermo-responsive multifunctional ionic conductive hydrogel by salt modulation strategy for multilevel encryption and visual monitoring

Despite the current progress in thermo-responsive materials, it is still a significant challenge to develop superior multiple temperature-sensitive ionic conductive hydrogels with programmable regulation capability for interactive wearable iontronics. Here, a dual thermo-responsive ionic conductive hydrogel (DTICH) is constructed based on a salt modulation strategy, which cleverly integrates low-temperature sensitive sodium dodecyl sulfate (SDS) and high-temperature sensitive poly(N-isopropylacrylamide) PNIPAm-based polymer. Owing to the common ion effect and salting-out effect, the resultant DTICH hydrogel visually presents wide and tunable dual temperature response behaviors of 0-18℃ (Tk) and 37-80℃ (LCST) by controlling NaCl concentration for the first time. Meanwhile, benefiting from the synergy of NaCl and thermo-sensitive materials, the hydrogel is concurrently endowed with excellent stretchability (>900 %), adhesion (adhesion strength >30 kPa), frost resisting (-40℃) and multilevel encryption functions. More importantly, the DTICH hydrogel can ingeniously perceive mechanical force and external temperature via the changes of relative resistance and transparency, which can be applied as human–computer interfaces to interactively monitor human motions and temperatures in real time. Therefore, our study establishes a brand new and effective route for the rational design and fabrication of high-level visual interactive devices and smart wearable iontronics.

Dual drug-loaded hydrogels with pH-responsive and antibacterial activity for skin wound dressing

Antibacterial and hemostatic properties are essential for wound healing dressing. In this study, a new type of hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid-aldehyde (HA-CHO) is fabricated by photo-crosslinking and respectively loaded with a single drug gentamicin sulfate (GS), and two drugs of GS and lysozyme (LZM). The composite hydrogel of GelMA and HA-CHO is successfully synthesized by the aldehyde and Schiff base reactions. The structures and compositions of the hydrogels with and without drug loaded are characterized by FT-IR, 1H NMR, and XPS. Furthermore, the microstructure and swelling behaviour of hydrogels prove that the content of HA-CHO has a significant role in the formation of hydrogels with dense porous structures and super absorbent. pH 7.4 and pH 5.0 conditions are used to evaluate the drug release behaviour of the obtained hydrogels. The released amount of GS of the drug-loaded hydrogels in the acidic buffer is more than that of the physiological environment because of the cleaved Schiff base bonds and the electrostatic interaction. Especially for the dual drug-loaded hydrogel GelMA/HA-CHO/GS/LZM, the released ratio of GS is elevated from 59 % in pH 7.4 buffer to about 78 % in pH 5.0 buffer within the first 6 h, which verifies the excellent pH-stimulus responsiveness. These endow the GS-LZM dual drug-loaded hydrogels with superior antibacterial efficiencies to that of the single GS drug-loaded hydrogels, no drug-loaded hydrogels, and SEBS control, especially in inhibiting S. aureus in a lower concentration of 106 CFU mL−1, which can be attributed to the synergistic effect of LZM and GS. For S. aureus at 106 CFU mL−1, the bacterial survival of GelMA/HA-CHO/GS/LZM is 1.1 %, which shows outstanding antibacterial effect. Hence, the drug-loaded hydrogels, especially the dual drug-loaded hydrogels with pH-responsive, antibacterial, and hemostatic properties have great potential as wound healing materials.

Immediate stress dissipation in dual cross-link hydrogels controls osteogenic commitment of mesenchymal stem cells

In vitro studies of mesenchymal stem cells (MSCs) differentiation have been predominantly performed with non-physiologically elastic materials. Here we report the effect of different viscoplastic ECM mimics on the osteogenic engagement of MSCs in 2D. We have developed soft hydrogels, composed of a lactose-modified chitosan, using a combination of permanent and temporary cross-links. The presence of temporary cross-links has a minor effect on the shear modulus of the hydrogels, but causes an immediate relaxation (dissipation) of the applied stress. This material property leads to early osteogenic commitment of MSCs, as evidenced by gene expression of runt-related transcription factor 2 (RUNX2), type 1 collagen (COL1A1), osteocalcin (OCN), alkaline phosphatase enzyme activity (ALP) and calcium deposit formation. In contrast, cells cultured on purely elastic hydrogels with only permanent cross-link begin to differentiate only after a longer period of time, indicating a dissipation-mediated mechano-sensing in the osteogenic commitment of MSCs.

Dual Stimuli-Responsive Polysaccharide Hydrogels Manufactured by Radiation Technique

This paper describes the results of the radiation-induced crosslinking of polysaccharides modified with hydroxypropyl and carboxymethyl functional groups, hydroxypropylcellulose (HPC) and carboxymethylcellulose (CMC), respectively, without and with poly(ethylene glycol) diacrylate (PEGDA) as a crosslinking agent, to obtain dual stimuli-responsive hydrogels. The gels were characterized in terms of water uptake and gel fraction, parameters that mainly depend on the HPC–CMC compositions, but also on the macromer crosslinker content and the absorbed dose. The swelling of hydrogels is controlled by both the temperature, due to the amphiphilic character of HPC and pH, due to the anionic functional groups of CMC. In spite of a similar degree of substitution in both cellulose derivatives, 1.4 for HPC and 1.2 for CMC, the pH response of hydrogels with an equal content of both polysaccharides is considerably higher—a reduction in swelling of up to 95% with a decrease in the pH to 2 was recorded—than the response to thermal-stimulus—wherein a reduction in swelling of less than 70% with an increasing in temperature to 55 °C was found. These biopolymers-based hydrogels of specific, stimuli-responsive swelling properties are anticipated in applications where a combination of two stimuli is essential and biodegradation may be required.

Dual stimuli-responsive hydrogels for colon targeted drug delivery.

Colon targeted drug deliverysystems are promising for the treatment of local diseases. The colon possessesa diverse microbiome that secretes a number of biomolecules, such as enzymes,that can be exploited for targeted drug delivery. Here, we report the synthesisof 2-hydroxyethyl methacrylate and methacrylic acid  copolymer hydrogels crosslinked with an enzyme-sensitivecrosslinking agent. The swelling and drug release properties of hydrogels were observedin pH 1.2, pH 6.5 and pH 7.4, and in the presence of rat cecal content. Swellingstudies revealed pH responsivity of the hydrogels while the release kinetics ofmetronidazole from hydrogels containing an enzyme-labile crosslinker were fasterin the presence of rat cecal content. The results show that dual responsive hydrogelscould provide a promising platform for colonic drug delivery

Dual peptide-functionalized hydrogels differentially control periodontal cell function and promote tissue regeneration.

Restoring the tooth-supporting tissues lost during periodontitis is a significant clinical challenge, despite advances in both biomaterial and cell-based approaches. This study investigated poly(ethylene glycol) (PEG) hydrogels functionalized with integrin-binding peptides RGD and GFOGER for controlling periodontal ligament cell (PDLC) activity and promoting periodontal tissue regeneration. Dual presentation of RGD and GFOGER within PEG hydrogels potentiated two key PDLC functions, alkaline phosphatase (ALP) activity and matrix mineralization, over either peptide alone and could be tuned to differentially promote each function. Hydrogel matrix mineralization, fostered by high concentrations of GFOGER together with RGD, identified a PDLC phenotype with accelerated matrix adhesion formation and expression of cementoblast and osteoblast genes. In contrast, maximizing ALP activity through high RGD and low GFOGER levels resulted in minimal hydrogel mineralization, in part, through altered PDLC pyrophosphate regulation. Transplantation of PDLCs in hydrogels optimized for either outcome promoted cementum formation in rat periodontal defects; however, only hydrogels optimized for in vitro mineralization improved new bone formation. Overall, these results highlight the utility of engineered hydrogel systems for controlling PDLC functions and their promise for promoting periodontal tissue regeneration.

Design, synthesis, and characterization of a novel dual cross-linked gelatin-based bioadhesive for hard and soft tissues adhesion capability

Many surgical treatments require a suitable tissue adhesive that maintains its performance in wet conditions and can be applied simultaneously for hard and soft tissues. In the present study, a dual cross-linked tissue adhesive was synthesized by mixing the gelatin methacryloyl (Gel-MA) and gelatin-dopamine conjugate (Gel-Dopa). The setting reaction was based on a photopolymerization process in the presence of a combination of riboflavin and triethanolamine and a chemical cross-linking process attributed to the genipin as a natural cross-linker. Modified gelatin macromolecules were characterized and the best wavelength for free radical generation in the presence of riboflavin was obtained. Tissue adhesives were prepared with 30% hydrogels of Gel-MA and Gel-Dopa with different ratios in distilled water. The gelation occurred in a short time after light irradiation. The chemical, mechanical, physical, and cytotoxicity properties of the tissue adhesives were evaluated. The results showed that despite photopolymerization, chemical crosslinking with genipin played a more critical role in the setting process. Water uptake, degradation behavior, cytotoxicity, and adhesion properties of the adhesives were correlated with the ratio of the components. The SEM images showed a porous structure that could ensure the entry of cells and nutrients into the surgical area. While acceptable properties in most experiments were observed, all features were improved as the Gel-Dopa ratio increased. Also, the obtained hydrogels revealed excellent adhesive properties, particularly with bone even after wet incubation, and it was attributed to the amount of gelatin-dopamine conjugate. From the obtained results, it was concluded that a dual adhesive hydrogel based on gelatin macromolecules could be a good candidate as a tissue adhesive in wet condition.

Dual-network polyacrylamide/carboxymethyl chitosan-grafted-polyaniline conductive hydrogels for wearable strain sensors

Conductive, wearable, and flexible hydrogel-based sensors are considered as promising applications in human motion detection and physiological signal monitoring. However, it is still a problem to integrate multiple functions into one material for the next-generation smart devices. Herein, we fabricated an ionic/electronic dual conductive hydrogel by combining the chemically crosslinked polyacrylamide (PAM) and the physically crosslinked carboxymethyl chitosan-grafted-polyaniline (CMCS-g-PANI)/Ag+ network. The double-network hydrogel displays a high stretchability, repeatable adhesiveness, antibacterial activities, and biocompatibility. It also has high sensitivity and stable electrical performance for wearable strain sensors. Furthermore, we assembled a self-powered strain sensor based on the conversion of chemical energy to electrical energy. It can be used for human motion detection even without external power supply. This work provides an avenue for the development of multifunctional hydrogels with outstanding mechanical and electronic performances for application in wearable electronic devices.

Multistimuli-responsive hydrogels with both anisotropic mechanical performance and anisotropic luminescent behavior

Anisotropic luminescence emission is the basis to achieve some key parameters in optoelectronic fields. As compared with mechanical anisotropy, however, achieving anisotropic emitting behavior is still challenging. Thus, integrating multiple stimuli into one luminescent hydrogel orthogonally while retaining its anisotropic structure remains an open challenge. Herein, we report the construction of a multistimuli-responsive mechanical/luminescent dual anisotropic hydrogel through the copolymerization of superparamagnetic nanoparticle-coated alumina (Fe/Al2O3) platelets, lanthanide complex, photochromic diarylethene molecule, and N-isopropylacrylamide (NIPA) in an oriented magnetic field. The aligned Fe/Al2O3 platelets impart the hydrogel an anisotropic mechanical property, and the orientation-dependent “shading effect” of the aligned Fe/Al2O3 platelets on the lanthanide complex also endow the hydrogel with anisotropic emission behavior. Significantly, photoreversible luminescence on/off switch and thermoreversible anisotropic deformation are realized in the hydrogel based on the conformation-dependent fluorescence resonance energy transfer between the lanthanide donor and photochromic diarylethene acceptor, and phase transition of polymerized NIPA, respectively. As a proof-of-concept, multidimensional intelligent anticounterfeiting is demonstrated by using this hydrogel. Thus, this work demonstrates a general preparation strategy of multistimuli-responsive dual anisotropic hydrogels for purposely designed applications, offering insights in the field fundamentally and practically.

Synthesis and characterization of an engineered dual crosslinked hydrogel system based on hyaluronic acid, chondroitin sulfate, and carboxymethyl chitosan with platelet‐rich plasma

AbstractHydrogels play a key role in cartilage tissue engineering (CTE) and cell transplantation. Idealy, the hydrogels designed for CTE should facilitate the formation of cartilage ECM, cilinically. However, challenges remain to engineer hydrogels with controllable responses, fast‐self recovery, and high stability. In the present study, a dual crosslinked hydrogel system based on the electrostatic and ionic bonds by mixing polymers composed of hyaluronic acid (HA), chondroitin sulfate (CS), and carboxymethyl chitosan (CMC) combined with platelet‐rich plasma (PRP) was successfully prepared. To increase the stability of hydrogel, 1‐Ethyl‐3‐(3‐dimethylamino propyl‐carbodiimide hydrochloride (EDC)/N‐hydroxy‐succinimide (NHS) was used as the crosslinking agent. The results revealed more stability of dual crosslinking hydrogel (HC54) due to proper stoichiometric ratio between polymers components and the crosslinking agent. According to the rheology results, a non‐Newtonian and viscoelastic behavior was recognized for all hydrogels and the highest mechanical property (modulus) of HC54 hydrogel was confirmed. Based on the SEM micrographs and weight loss analysis, the lowest degradation rate was observed for the HC54 hydrogel after immersion in phosphate buffered saline solution. PRP release from the hydrogel was analyzed with the Bradford assay method and a cumulative release of 50 percent during 15 days was found. Finally, the MTT assay conducted on dual crosslinked HA/CS/CMC hydrogel with and without PRP both demonstrated cytocompatibility of hydrogel while the presence of PRP enhanced the cell viability.

Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma

Post-resection recurrence remains an intractable problem in hepatocellular carcinoma (HCC) management. Natural killer (NK) cell infusion is considered as a promising cancer therapy, but acidic tumor microenvironment (TME) and neutrophil extracellular traps (NETs) greatly counteract its efficacy. Recently, polymer hydrogels have aroused much interest in tumor combination therapy, since they load and controllably release therapeutic agents with high bioavailability and low systemic toxicity. Therefore, a biocompatible hydrogel with tumor acidity neutralizer and NETs lyase may show promise for enhancing NK infusion to prevent post-resection HCC recurrence. Herein, a dual pH-responsive hydrogel with tumor acidity neutralizer (mesoporous bioactive glass nanoparticles) and NETs lyase (Deoxyribonuclease I, DNase I) is developed and used in combination with NK cell infusion for preventing post-resection HCC recurrence. The hydrogel can be injected to surgical margin and form an adhesive gel with a rapid hemostasis. Besides, it neutralizes tumor acidity to reduce tumor infiltration of immunosuppressive cells, and releases DNase I in a pH-responsive manner to degrade NETs. Moreover, this combination therapy significantly enhances NK cell infusion to combat post-surgical HCC recurrence without systemic toxicity. This study provides proof of concept that combination of NK cell adoptive therapy and hydrogel-based delivery system can successfully prevent post-resection HCC recurrence.

Injectable metronidazole-eluting gelatin-alginate hydrogels for local treatment of periodontitis.

Infection of the periodontal pocket presents two major challenges for drug delivery: administration into the periodontal pocket and a high fluid clearance rate in the pocket. The current study aimed to develop and study a novel hydrogel system for delivery of the antibiotic drug metronidazole directly into the periodontal pocket via injection followed by in situ gelation. The natural polymers gelatin and alginate served as basic materials, and their crosslinking using a carbodiimide resulted in a dual hydrogel network. The study focused on the effects of the hydrogel's formulation parameters on the drug release profile and the hydrogel's physical and mechanical properties. A cell viability test was conducted on human fibroblasts. The metronidazole-loaded hydrogels demonstrated a decreasing release rate with time, where most of the drug eluted within 24h. These hydrogels exhibited fibroblast viability of at least 75% after 24 and 48h, indicating that they are highly biocompatible. Although the alginate concentration used in this study was relatively low, it had a strong effect on the physical as well as the mechanical properties of the hydrogel. An increase in the alginate concentration increased the crosslinking rate and enabled enhanced entanglement of the 3D structure, resulting in a decrease in the gelation time (less than 10s) and swelling degree, which are both desired for the studied periodontal application. Increasing the gelatin concentration without changing the crosslinker concentration resulted in significant changes in the physical properties and slight changes in the mechanical properties. Metronidazole incorporation slightly decreased the hydrophilicity of the hydrogel and therefore also its viscosity, and affected the sealing ability and the tensile and compression moduli. The developed hydrogels exhibited controllable mechanical and physical properties, can target a wide range of conditions, and are therefore of high significance in the field of periodontal treatment.

Preparation and properties of O-chitosan quaternary ammonium salt/polyvinyl alcohol/graphene oxide dual self-healing hydrogel

A simple method had been developed through O-chitosan quaternary ammonium salt (O-HACC), polyvinyl alcohol (PVA) and graphene oxide (GO) to prepare O-HACC/PVA/GO dual self-healing bacteriostatic hydrogels. Then the hydrogels and materials were characterized by FT-IR, X-RD, 1H NMR, SEM and TG. The hydrogel's compressive strength, equilibrium swelling and bacteriostatic efficiency were systematically studied. The research results showed that the maximum equilibrium swelling rate of hydrogel was 720%, the maximum compressive strength was 1500 Pa, and could self-heal within 12 h. In addition, the hydrogel could effectively inhibit E. coli and S. aureus, and also showed a good release behavior for bovine serum albumin (BSA). The CCK-8 method proved that the hydrogel was non-toxic to murine fibroblasts and could promote cell proliferation and growth to a certain extent. This research has potential significance for the application of self-healing hydrogel materials in the field of biomedicine.

Development of a Biomimetic Extracellular Matrix with Functions of Protein Sequestration and Cell Attachment Using Dual Aptamer-Functionalized Hydrogels.

The extracellular matrix (ECM) has not only cell-binding sites for cell attachment but also protein-binding sites for molecular sequestration. Aptamers have high binding affinities and specificities against their target molecules. Thus, the purpose of this work was to develop dual aptamer-functionalized hydrogels for simultaneously recapitulating the two key features of the ECM in binding cells and sequestering proteins. We synthesized the hydrogels using free-radical polymerization in a freezing procedure. As the hydrogels were macroporous with pores of 40-50 μm, both cells and proteins could be loaded into the hydrogels after the synthesis. Importantly, the vascular endothelial growth factor (VEGF) aptamer improved VEGF sequestration and reduced the apparent diffusivity of VEGF by over 2 orders of magnitude, resultantly prolonging VEGF retention and release. The c-MET aptamer promoted the attachment of endothelial cells in the hydrogel network. When two aptamers were both incorporated into the hydrogel, they could produce synergistic effects on cell survival and growth. Thus, this work has successfully demonstrated the potential of developing biomimetic ECMs with two key functions of cell attachment and protein sequestration using dual aptamer-functionalized hydrogels.

Solvents Triggered Coil-to-Globule-to-Coil Transition of Dual Nanocomposite Hydrogels with Inorganic Hybrid Crosslinking

This paper presents the study on the reentrant solvation of dual nanocomposite hydrogel poly-N-isopropylacrylamide/Laponite/SiO2 (PNIPAM/Laponite/SiO2) upon shrinkage/reswelling process. Depending on the unique hierarchical microstructure of inorganic hybrid crosslinking of Laponite and SiO2, as well as the preferential interaction of polar solvents with PNIPAM chains, the hydrogel exhibited rapid coil-to-globule-to-coil transition in water-polar solvent mixtures. The solvation behavior could be controlled through varying types of organic solvents. Shrinkage in water-polar solvent mixtures occurred as a consequence of strong interaction between polar solvents and PNIPAM chains, whereas reswelling resulted from the direct interaction of the solvent molecules with the intermolecular water in the hydrogel. The attractive competing effects on forming hydrogel-water and hydrogel-polar solvent hydrogen bonds were considered to be indis-pensable to the solvation. The rapid response rate was attributed to the synergistic effect of the unique hetero-geneous microstructure with inorganic hybrid crosslinking and preferential interaction of polar solvents with polymer chains. The mechanism proposed in this paper provides a new reference on design of smart soft mat-ter systems. Moreover, several solvation effects described in this paper can be incorporated in theory of cononsolvent-induced conformational transitions in the nanocomposite hydrogels with inorganic hybrid crosslinking.

A rapidly responsive, controllable, and reversible photo-thermal dual response hydrogel

In this work, the double network structure was used to make the hydrogel possess photo-thermal dual-responsive properties. N-isopropylacrylamide (NIPAM) was first introduced into polyacrylamide (PAM) and sodium alginate (SA) hydrogels to obtain double network hydrogels (PAM-SA-PNIPAM) by in-situ polymerization. PNIPAM imparted thermally responsive properties to the hydrogels. Ammonium molybdate ((NH4)6Mo7O24) was then introduced into the PAM-SA-PNIPAM hydrogel by immersion to obtain a dual network hydrogel (DN-SA) with photothermal dual responsive properties. The prepared DN-SA hydrogels can change from colorless transparent to white opaque within 10s at 40 °C; under 365 nm UV irradiation, they can change from colorless to dark blue in about 3min. More importantly, this conversion of transparency and color is reversible, and the results of multiple cycle experiments show that DN-SA hydrogel can be used repeatedly. On this basis, the two-dimensional code that can be scanned by cell phone was printed on DN-SA hydrogel using UV light, and the printed QR code can eliminate itself after 48 h, which means DN-SA hydrogel is expected to be applied in the field of self-erasable information storage.

Physically motivated models of polymer networks with dynamic cross-links: comparative study and future outlook

Polymer networks consisting of a mixture of chemical and physical cross-links are known to exhibit complex time-dependent behaviour due to the kinetics of bond association and dissociation. In this article, we highlight and compare two recent physically based constitutive models that describe the nonlinear viscoelastic behaviour of such transient networks. These two models are developed independently by two groups of researchers using different mathematical formulations. Here, we show that this difference can be attributed to different viewpoints: Lagrangian versus Eulerian. We establish the equivalence of the two models under the special situation where chains obey Gaussian statistics and steady-state bond dynamics. We provide experimental data demonstrating that both models can accurately predict the time-dependent uniaxial behaviour of a poly(vinylalcohol) dual cross-link hydrogel. We review the advantages and disadvantages of both approaches in applications and close by discussing a list of open challenges and questions regarding the mathematical modelling of soft, viscoelastic networks.

Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm

The SARS-CoV-2 pandemic spread worldwide unabated. However, achieving protection from the virus in the whole respiratory tract, avoiding blood dissemination, and calming the subsequent cytokine storm remains a major challenge. Here, we develop an inhaled microfluidic microsphere using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from angiotensin-converting enzyme II (ACE2) receptor-overexpressing cells and macrophages. By timely competing with the virus for ACE2 binding, the inhaled microspheres significantly reduce SARS-CoV-2 infective effectiveness over the whole course of the respiratory system in vitro and in vivo. Moreover, the inhaled microspheres efficiently neutralize proinflammatory cytokines, cause an alternative landscape of lung-infiltrated immune cells, and alleviate hyperinflammation of lymph nodes and spleen. In an acute pneumonia model, the inhaled microspheres show significant therapeutic efficacy by regulation of the multisystem inflammatory syndrome and reduce acute mortality, suggesting a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration.

Dual antioxidant-photosensitizing hydrogel system: Cross-linking of chitosan with tannic acid for enhanced photodynamic efficacy

Herein, a new antioxidant-photosensitizing hydrogel based on chitosan has been developed to control photodynamic therapy (PDT) activity in cancer treatment. In PDT, photosensitizers generate reactive oxygen species (ROS) during photochemical reactions, leading oxidative damage to cancer cells. However, high ROS levels are lethal to non-target healthy cells and tissues such as endothelial cells and blood cells. To mediate these drawbacks, we improved PDT with a natural polyphenolic antioxidant, Tannic acid (TA), to control the ROS level and minimize side effects through singlet oxygen (1O2) scavenging. In this work, chitosan-based hydrogels were designed using tannic acid as an antioxidant cross-linker and loaded with water-soluble N, N′-di-(l-alanine)-3,4,9,10-perylene tetracarboxylic diimide (PDI-Ala) as a photosensitizer. Our results showed that the hydrogel formed a three-dimensional (3D) microstructure with good mechanical strength and significant singlet oxygen production and antioxidant activity. In addition, the behavior of human melanoma cell line A375 and dental pulp stem cells (as normal cells) was compared and studied during an in vitro photodynamic treatment. Normal cells had a higher viability than cancer cells, indicating that the PDT is more effective on cancer cells than on normal cells. The new hydrogels could be applied as an effective new drug to control PDT performance.