N-carboxyethyl Chitosan Research Articles

A novel red fluorescent and dynamic nanocomposite hydrogel based on chitosan and alginate doped with inclusion complex of carbon dots

Red fluorescent hydrogels possessing injectable and self-healing properties have widespread potential in biomedical field. It is still a challenge to achieve a biomacromolecules based dynamic hydrogels simultaneously combining with excellent red fluorescence, good mechanical properties, and biocompatibility. Here we first explore hydrophilic inclusion complex of (R-CDs@α-CD) derived from hydrophobic red fluorescent carbon dots (R-CDs) and α-cyclodextrin (α-CD), and then achieved a red fluorescent and dynamic polysaccharide R-CDs@α-CD/CEC-l-OSA hydrogel. The nanocomposite hydrogel can be fabricated through controlled doping of red fluorescent R-CDs@α-CD into dynamic polymer networks, taking reversibly crosslinked N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) as an example. The versatile red fluorescent hydrogel simultaneously combines the features of injection, biocompatibility, and augmented mechanical properties and self-healing behavior, especially in rapid self-recovery even after integration. The R-CDs@α-CD uniformly dispersed into dynamic hydrogel played the role of killing two birds with one stone, that is, endowing red emission of a hydrophilic fluorescent substance, and improving mechanical and self-healing properties as a dynamic nano-crosslinker, via forming hydrogen bonds as reversible crosslinkings. The novel red fluorescent and dynamic hydrogel based on polysaccharides is promising for using as biomaterials in biomedical field.

Cell-adhesive double network self-healing hydrogel capable of cell and drug encapsulation: New platform to construct biomimetic environment with bottom-up approach

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.

Multifunctional hydrogel for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer recurrence and wound infection

Metastatic recurrence and postoperative wound infection are two major challenges for breast cancer patients. In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer and wound infection. The hydrogel system was obtained by cross-linking Prussian blue-modified N-carboxyethyl chitosan (PBCEC) and oxidized sodium alginate using the amino and aldehyde groups on the polysaccharides, resulting in the formation of responsive dynamic imine bonds. Conditioned stimulation (e.g., acid microenvironment) enabled the controlled swelling of hydrogels as well as subsequent slow release of loaded doxorubicin (DOX). Additionally, this hydrogel system decomposed endogenous reactive oxygen species into oxygen to relieve the hypoxic tumor microenvironment and promote the healing of infected-wounds. Both in vitro and in vivo experiments demonstrated the synergistic reoxygenation and chemo/photothermal effects of the PB/DOX hydrogel system against metastatic breast cancer and its recurrence, as well as postoperative wound infection. Thus, the combination of reoxygenation and chemo/photothermal therapy represents a novel strategy for treating and preventing tumor recurrence and associated wound infection.

Chitosan based macromolecular hydrogel loaded total glycosides of paeony enhances diabetic wound healing by regulating oxidative stress microenvironment

Oxidative stress microenvironment caused by reactive oxygen species (ROS) accumulation seriously hinders wound healing in diabetes, which brings great burden to global health. Various wound dressings on the market focus on delivering active substances to promote wound healing in diabetes. However, the complex pathological microenvironment of diabetic wounds often leads to the inactivation of delivery factors, which often leads to treatment failure, and thus, emerging therapeutic approaches are urgently needed. In this study, a macromolecular hydrogel synthesized by crosslinking N-carboxyethyl chitosan, hyaluronic acid-aldehyde, and adipic acid dihydrazide, with self-healing and injectable abilities was used to deliver total glycosides of paeony (TGP). The TGP incorporated hydrogel could obviously induce fibroblasts proliferation and secretion of various extracellular matrix proteins and growth factors, induce migration and angiogenesis of vein endothelial cells, and enhance macrophages polarization to M2 phenotype by eliminating accumulated ROS. In diabetic wound models, the ROS-scavenging hydrogel efficiently enhanced proliferation, re-epithelialization, collagen deposition, as well as angiogenesis in the wound area. Besides, the dressing induced the macrophages polarization from M1 phenotype (pro-inflammatory) to M2 phenotype (anti-inflammatory) and decreased the levels of inflammatory cytokines, thereby enhancing the diabetic wound healing. The wounds treated with TGP incorporated hydrogel almost completely healed 16 days after treatment. However, the residual wound areas in the groups of Con, INTRA, and Gel are 55.2 ± 4.6 %, 33.7 ± 6.5 %, and 34.9 ± 6.1 % on the 16th day, respectively. This hydrogel with pathological microenvironment improvement ability affords a novel therapeutic strategy for enhancing healing of chronic diabetic wound.

Bioabsorbable Fibrillar Gauze Dressing Based on N-Carboxyethyl Chitosan Gelling Fibers for Fatal Hemorrhage Control.

Death from lethal hemorrhage remains a major problem in various emergency scenarios. There is a continuous interest in the development of absorbable hemostatic dressings that can control hemorrhage rapidly and can be left in the wound site without removal. In this study, we report a hemostatic gauze dressing based on N-carboxyethyl chitosan (CECS) gelling fibers. The CECS fibrillar gauze combines ultra-hydrophilic, cationic chemical property of the fiber components with the fluffy nonwoven material form, exhibiting good conformability for wound filling, high fluid uptaking capacity, and enhanced blood-concentrating effect. In a swine femoral artery injury model, the CECS fibrillar gauze achieves shorter time to hemostasis and less blood loss compared with commercially available hemostatic dressings. This chitosan gelling fiber gauze demonstrates comparable bioabsorbability to clinically used absorbable hemostat and thus may be applied to treat fatal hemorrhage both in emergency medical services and in internal surgical procedures.

Graphene oxide-based injectable conductive hydrogel dressing with immunomodulatory for chronic infected diabetic wounds

The main challenges of chronic wounds represented by diabetic wounds are that the infection is not easily controlled and the healing is difficult, mainly due to the high-glucose microenvironment, M1 macrophage aggregation, and persistent inflammation. Previous studies inspired by endogenous electric fields have demonstrated that conductive materials can promote cell proliferation, migration, etc., to promote wound healing. However, no study has been conducted on the effect of conductive materials on local immunity. To this end, this study designed a graphene oxide-based conductive hydrogel to repair infected diabetic wounds. Self-healing injectable conductive hydrogels were synthesized by dynamic Schiff-base reaction and electrostatic interactions between oxidized hyaluronic acid, N-carboxyethyl chitosan, graphene oxide, and polymyxin B. The study found that the hydrogel has good biocompatibility and antibacterial properties. In addition, in vivo experiments confirmed that the hydrogel could modulate macrophage polarization to improve the local inflammatory microenvironment, promote neovascularization, and significantly accelerate the healing of diabetic wounds. Most notably, graphene oxide-based conductive hydrogels can modulate local immunity in diabetic wounds to promote healing. This study provides new guidelines for expanding research on conductive materials and new directions for promoting healing in infected diabetic wounds.

Injectable hydrogel based on dodecyl-modified N-carboxyethyl chitosan/oxidized konjac glucomannan effectively prevents bleeding and postoperative adhesions after partial hepatectomy

Hemostasis and prevention of postoperative adhesions after hepatectomy are still challenges. In this work, we chose chitosan, a competitive candidate hemostatic material, as the backbone, and konjac glucomannan as the functional moieties, to form an injectable hydrogel. The hydrogel was prepared by the Schiff base reaction of dodecyl-modified N-carboxyethyl chitosan (DCEC) and oxidized konjac glucomannan (OKGM), which could effectively prevent bleeding and postoperative adhesions. The resultant hydrogel possessed self-healing and tissue adhesive capability, and combined the unique bioactivities of two polysaccharides: DCEC endowed the hydrogel with excellent antibacterial and hemostatic ability by the electrostatic and hydrophobic interactions between the cell membrane and amine/dodecyl groups, and OKGM imparted hydrogel anti-inflammatory action by activating macrophages. Moreover, the notable hemostatic efficacy of the hydrogel was confirmed in a rat hepatectomy model. The hydrogel could prevent postoperative adhesions and down-regulate the inflammatory factor TNF-α and the pro-fibrotic factor TGF-β1 in situ, which might be caused by the combination of the barrier function of hydrogel and instinct bioactivities of DCEC and OKGM. Thus, this multifunctional injectable hydrogel is potentially valuable for preventing bleeding and postoperative adhesions after hepatectomy.

PH-responsive hydrogel loaded with insulin as a bioactive dressing for enhancing diabetic wound healing

The healing of diabetic foot ulcers (DFUs) is a major challenge for clinical treatment because of the hyperglycemic and acidic microenvironment in the wound area. In this study, a self-healing, injectable, and pH-responsive hydrogel was synthesized by N-carboxyethyl chitosan (N-chitosan), hyaluronic acid–aldehyde (HA-ALD), adipic acid dihydrazide (ADH) through the formation of the reversible dynamic bonds, acylhydrazone and imine bonds. The presence of the acylhydrazone bond characterizes the hydrogel pH-responsive property. In this study, the insulin glargine was successfully incorporated into the hydrogel, allowing its sustained and pH-responsive releasing from the hydrogel for up to 14 days. The hydrogel presented good compatibility and pore structure, and the insulin released from the hydrogel maintained its original bioactivity. Full thickness wounds were established on the feet of diabetic rats to evaluate the therapeutic effect of the dressing. The results revealed that the bioactive insulin-loaded hydrogel dressing shortened the inflammatory phase, enhanced granulation tissue formation, promoted collagen deposition, accelerated re-epithelialization and neovascularization, and postponed or even improved peripheral neuropathy, thus, significantly accelerated DFUs healing. Our findings showed that the insulin-loaded hydrogels had promising potential as a multifunctional bioactive wound dressing for enhancing DFUs healing.

A simple polysaccharide based injectable hydrogel compositing nano-hydroxyapatite for bone tissue engineering

The biomaterials based injectable hydrogel showed great potential as bone tissue engineering scaffold for its biocompatibility, injectable nature and interconnected porous structure that favors loading bioactive substances or cells for bone repair. In this study, N-carboxyethyl chitosan (NCEC) and oxidized dextran (ODex) was synthesized to fabricate a simple polysaccharide injectable hydrogel based on Schiff base crosslinking (dynamic imine bonds), to composite nano-hydroxyapatite (nHAP) for rat cranial bone repair. The polysaccharide hydrogel displayed interconnected porous structure and suitable rheological properties for compositing nHAP. Biochemical properties of the hydrogel were not affected through the composition of nHAP. In vivo cranial bone repair results showed excellent bone repair effect of the composite materials, demonstrating the simply constructed polysaccharide hydrogel is suitable as bone tissue engineering scaffold.

Intra-articular Injection of Chitosan-Based Supramolecular Hydrogel for Osteoarthritis Treatment

Background:Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy.Methods:In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD).Results:This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection.Conclusion:This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.

Thermoresponsive and Conductive Chitosan-Polyurethane Biocompatible Thin Films with Potential Coating Application.

Conductive thin films have great potential for application in the biomedical field. Herein, we designed thermoresponsive and conductive thin films with hydrophilicity, strain sensing, and biocompatibility. The crosslinked dense thin films were synthesized and prepared through a Schiff base reaction and ionic interaction from dialdehyde polyurethane, N-carboxyethyl chitosan, and double-bonded chitosan grafted polypyrrole. The thin films were air-dried under room temperature. These thin films showed hydrophilicity and conductivity (above 2.50 mS/cm) as well as responsiveness to the deformation. The tensile break strength (9.72 MPa to 15.07 MPa) and tensile elongation (5.76% to 12.77%) of conductive thin films were enhanced by heating them from 25 °C to 50 °C. In addition, neural stem cells cultured on the conductive thin films showed cell clustering, proliferation, and differentiation. The application of the materials as a conductive surface coating was verified by different coating strategies. The conductive thin films are potential candidates for surface modification and biocompatible polymer coating.

Injectable Self-Healing Hydrogels Containing CuS Nanoparticles with Abilities of Hemostasis, Antibacterial activity, and Promoting Wound Healing.

Injectable self-healing hydrogels containing functional nanoparticles (NPs) have attracted much attention in many fields of biomedicine. A series of injectable self-healing hydrogels containing PEGylation CuS NPs based on N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OA) were developed by taking advantages of the unique functions of CuS NPs and chitosan, referred to as CuS NP hydrogels or CEC-OAm-CuSn, where "m" stands for the concentration percentage of the added OA solution (w/v) and "n" represents the molar concentration of CuS NPs in the hydrogels. The physical properties of CuS NP hydrogels, syringeability, rapid self-repair ability, and photothermal performance were systematically investigated. The multiple functions for CuS NP hydrogels requested in the skin healing process were explored. The results showed that CuS NP hydrogels had not only adjustable physical properties and good injectable self-healing characteristics but also excellent functionalities, concurrently including hemostatic ability, bacteria killing capability, and cell migration and proliferation promotion. In vivo wound healing and histomorphological examinations of immunofluorescence staining in a mouse full-thickness wound model demonstrated good acceleration effects of these hydrogels for infected wound healing. Therefore, these injectable self-healing CuS NP hydrogels which possess the abilities of hemostasis, antibacterial activity, and infected-wound healing promotion exhibit great potential as in situ wound dressings.

An injectable hydrogel with pH-sensitive and self-healing properties based on 4armPEGDA and N-carboxyethyl chitosan for local treatment of hepatocellular carcinoma

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.

Conductive adhesive self-healing nanocomposite hydrogel wound dressing for photothermal therapy of infected full-thickness skin wounds

Bacteria-infected wounds and antibiotics abuse have become significant burdens to patients and medical systems. Thus, designing a non-antibiotic-dependent multifunctional wound dressing for treating bacteria-infected wounds is urgently desired. Herein, a series of conductive self-healing and adhesive nanocomposite hydrogels with a remarkable photothermal antibacterial property based on N-carboxyethyl chitosan (CEC) and benzaldehyde-terminated Pluronic F127/carbon nanotubes (PF127/CNT) were developed, and their great potential as agents for photothermal therapy (PTT) of infected wounds was demonstrated in vivo. The hydrogels exhibited a suitable gelation time, stable mechanical properties, hemostatic properties, high water absorbency, and good biodegradability. After loading the antibiotic moxifloxacin hydrochloride, the hydrogels showed a pH-responsive release profile and good antibacterial activity. The tissue adhesive property of the hydrogels allowed them to have a good hemostatic effect in a mouse liver trauma model, mouse liver incision model, and mouse tale amputation model. The addition of CNTs endowed the hydrogel with in vitro/in vivo photothermal antimicrobial activity and good conductivity. An in vivo experiment in a mouse full-thickness skin wound-infected model indicated that the hydrogels had an excellent treatment effect leading to significantly enhanced wound closure healing, collagen deposition, and angiogenesis. In summary, these conductive photothermal self-healing nanocomposite hydrogels as multifunctional wound dressing exhibit great potential for the treatment of infected wounds.

Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.

Degradable conductive injectable hydrogels as novel antibacterial, anti-oxidant wound dressings for wound healing

Besides preventing wound infection, novel wound dressing materials are highly expected to exhibit the extraordinary wound repair and skin regeneration advantage. Herein, we designed a kind of multi-functional injectable hydrogel dressing, integrating the conductivity, desirable antioxidant ability and antibacterial property to meet increasing requirements of skin damage. By mixing the biocompatible polymer N-carboxyethyl chitosan (CEC) and oxidized hyaluronic acid-graft-aniline tetramer (OHA-AT) polymer under physiological conditions, the conductive anti-oxidant hydrogels OHA-AT/CEC were fabricated. The hydrogels exhibited stable rheological property, high swelling ratio, suitable gelation time, good in vitro biodegradation property, electroactive property and free radical scavenging capacity. With the antibiotic amoxicillin addition, the hydrogel showed good antibacterial property to effectively prevent the wound infection. In vivo experiments indicated that hydrogel with AT addition (OHA-AT/CEC hydrogels) significantly accelerated wound healing rate with higher granulation tissue thickness, collagen disposition and more angiogenesis in a full-thickness skin defect model. In one word, the present approach can shed new light on designing of electroactive injectable hydrogels with promising applications in wound dressing.

Degradable conductive self-healing hydrogels based on dextran-graft-tetraaniline and N-carboxyethyl chitosan as injectable carriers for myoblast cell therapy and muscle regeneration

Injectable conductive hydrogels have great potential as tissue engineering scaffolds and delivery vehicles for electrical signal sensitive cell therapy. In this work, we present the synthesis of a series of injectable electroactive degradable hydrogels with rapid self-healing ability and their potential application as cell delivery vehicles for skeletal muscle regeneration. Self-healable conductive injectable hydrogels based on dextran-graft-aniline tetramer-graft-4-formylbenzoic acid and N-carboxyethyl chitosan were synthesized at physiological conditions. The dynamic Schiff base bonds between the formylbenzoic acid and amine group from N-carboxyethyl chitosan endowed the hydrogels with rapid self-healing ability, which was verified by rheological test. Equilibrated swelling ratio, morphology, mechanical strength, electrochemistry and conductivity of the injectable hydrogels were fully investigated. The self-healable conductive hydrogels showed an in vivo injectability and a linear-like degradation behavior. Two different kinds of cells (C2C12 myoblasts and human umbilical vein endothelial cells (HUVEC)) were encapsulated in the hydrogels by self-healing effect. The L929 fibroblast cell culture results indicated the biocompatibility of the hydrogels. Moreover, the C2C12 myoblast cells were released from the conductive hydrogels with a linear-like profile. The in vivo skeletal muscle regeneration was also studied in a volumetric muscle loss injury model. All these data indicated that these biodegradable self-healing conductive hydrogels are potential candidates as cell delivery vehicles and scaffolds for skeletal muscle repair. Statement of SignificanceInjectable hydrogels with self-healing and electrical conductivity properties are excellent candidates as tissue-engineered scaffolds for myoblast cell therapy and skeletal muscle regeneration. The self-healing property of these hydrogels can prolong their lifespan. However, most of the reported conductive hydrogels are not degradable or do not have the self-healing ability. Herein, we synthesized antibacterial conductive self-healing hydrogels as a cell delivery carrier for cardiac cell therapy based on chitosan-grafted-tetraaniline hydrogels synthesized in our previous work. However, an acid solution was used to dissolve the polymers in that study, which may induce toxicity to cells. In this work, we synthesized a series of injectable electroactive biodegradable hydrogels with rapid self-healing ability composed of N-carboxyethyl chitosan (CECS) and dextran-graft-aniline oligomers, and these hydrogel precusor can dissolve in PBS solution of pH 7.4; we further demonstrated their potential application as cell delivery vehicles for skeletal muscle regeneration.

Interfacial Compression-Dependent Merging of Two Miscible Microdroplets in an Asymmetric Cross-Junction for In Situ Microgel Formation

Controlling the merging of different microdroplets in a microfluidics system could generate a multitude of complex droplets because of their inherent surface tension, but poses a significant challenge because of their high surface tension. Here, a novel microfluidic merging technique is introduced using an asymmetric cross-junction geometry which increases the interfacial compression between two microdroplets. Microdroplets of two viscous polymer solutions, oxidized dextran (ODX) and N-carboxyethyl chitosan (N-CEC), which can undergo a crosslinking reaction via Schiff base formation, are allowed to merge at the asymmetric cross-junction without the assistance of additional merging schemes. The N-CEC and ODX microdroplets being formed at their orifices contact at a more favorable position to overcome their interfacial tension through this asymmetric geometry, until the interfacial layer breaks and pushes the former (with higher viscosity) into the latter. On the other hand, a typical symmetric cross-junction geometry cannot induce merging, because of insufficient interfacial compression generated by direct collision between two droplets. The merged N-CEC and ODX droplets soon become completely homogeneous via diffusion, ultimately leading to in situ microgel formation. Changing the concentration of ODX further controls the crosslinking density of the microgels. In addition, the viability of cells encapsulated within the microgels is well maintained, demonstrating the biocompatibility of the entire process. Taken together, the microfluidic merging technique introduced here could be broadly applicable for engineering cell-encapsulated microgels for biomedical applications.

(Invited) Self-healing Polysaccharide-based Hydrogels as Injectable Carriers for Neural Stem Cells

Self-healing injectable hydrogels can be formulated as three-dimensional carriers for the treatment of neurological diseases with desirable advantages, such as avoiding the potential risks of cell loss during injection, protecting cells from the shearing force of injection. However, the demands for biocompatible self-healing injectable hydrogels to meet above requirements and to promote the differentiation of neural stem cells (NSCs) into neurons remain a challenge. Herein, we developed a biocompatible selfhealing polysaccharide-based hydrogel system as a novel injectable carrier for the delivery of NSCs. N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) are the main backbones of the hydrogel networks, denoted as CEC-l-OSA hydrogel (“l” means “linked-by”). Owing to the dynamic imine cross-links formed by a Schiff reaction between amino groups on CEC and aldehyde groups on OSA, the hydrogel possesses the ability to self-heal into a integrity after being injected from needles under physiological conditions. The CEC-l-OSA hydrogel in which the stiffness mimicking nature brain tissues (100~1000 Pa) can be finely tuned to support the proliferation and neuronal differentiation of NSCs. The multi-functional, injectable, and self-healing CEC-l-OSA hydrogels hold great promises for NSC transplantation and further treatment of neurological diseases.

Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair

The fabrication of osteochondral tissue engineering scaffolds comprised of different layers is a big challenge. Herein, bilayers comprised of double network hydrogels with or without nano hydroxyapatite (HAp) were developed by exploiting the radical reaction of poly(ethylene glycol) diacrylate (PEGDA) and the Schiff-base reaction of N-carboxyethyl chitosan (CEC) and oxidized hyaluronic acid sodium (OHA) for osteochondral tissue engineering. The bilayered osteochondral scaffold was successfully fabricated based on the superior self-healing property of both hydrogels and evaluated by scanning electron microscopy, macroscopic observation and mechanical measurements. In addition, the hydrogels exhibited good biocompatibility as demonstrated by the in vitro cytotoxicity and in vivo implantation tests. The results indicated that the bilayered hydrogel had great potential for application in osteochondral tissue engineering.