Progress in chitin/chitosan and their derivatives for biomedical applications: Where we stand.

Chitin and its deacetylated form, chitosan, have demonstrated remarkable versatility in the realm of biomaterials. Their exceptional biocompatibility, antibacterial properties, pro- and anticoagulant characteristics, robust antioxidant capacity, and anti-inflammatory potential make them highly sought-after in various applications. This review delves into the mechanisms underlying chitin/chitosan's biological activity and provides a comprehensive overview of their derivatives in fields such as tissue engineering, hemostasis, wound healing, drug delivery, and hemoperfusion. However, despite the wealth of studies on chitin/chitosan, there exists a notable trend of homogeneity in research, which could hinder the comprehensive development of these biomaterials. This review, taking a clinician's perspective, identifies current research gaps and medical challenges yet to be addressed, aiming to pave the way for a more sustainable future in chitin/chitosan research and application.

Highly Soft, Abrasion-Resistant, and Moisture-Absorbent Wool/PA56 Blended Yarns for Seating Fabrics.

Biobased nylon (PA56) not only has the same physical properties as nylon (PA6/PA66) but its production method is also more environmentally friendly. PA56 fabric has the advantages of moisture absorption, perspiration, high-temperature resistance, and flexibility, which have been widely studied by scientific researchers. Wool has the advantages of beauty, environmental protection, and anti-wrinkle. However, pure wool fabrics have low strength and are easy to shrink when washed, which has always been a problem. Hence, this work adopted the ring spinning method to prepare wool/PA56 blended yarn with wool content of 0, 10, 30, 50, 70, and 100 wt%. Thus, to examine the effects of different blending ratios and twists on yarn performance, PA56 was blended with wool. The results showed that findings indicate that yarn performance is influenced by both yarn twist and blending ratio. The yarn thickens and takes on more linear density as the blending ratio and yarn twist increase. As the wool ratio increases, the yarn's breaking stress and breaking strain decrease. It is obvious that the strength and elongation at break of pure PA56 yarn are 2.09 cN/Dtex and 33.92%, respectively. When the wool content was 100 wt%, the strength and elongation at break of the blended yarn were 0.66 cN/Dtex and 21.15%, respectively. With the amount of wool blending, the yarn hairiness index's H-value initially rises and subsequently falls. The percentage of blended wool reaches 50% at 2.14; less blending might exacerbate the yarn's stem, resulting in neps and unevenness features. The quality of the yarn improves as the blending percentage rises. The yarn has the advantages of resource saving, biodegradability, and environmental friendliness and has a broad application prospect in the automotive interior field.

Hemoperfusion Adsorbents for Removal of Common Toxins in Liver and Kidney Failure: Recent Progress, Challenges, and Prospects.

Liver and kidney failure can lead to extensive accumulation of toxic metabolites in the blood and tissues, such as bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea, which aggravate the progression of the disease. Hemoperfusion can effectively adsorb and remove toxins from the blood and treat liver and kidney failure. However, the adsorption efficiency and safety of traditional hemoperfusion adsorbents are not ideal. Thus, it is urgent to develop adsorbents with good blood compatibility, as well as high adsorption and strong selective capacities, to fulfill the clinical needs. In recent years, new hemoperfusion adsorbents with improved adsorption performance and good blood compatibility have been developed. This review classifies and summarizes the recent research progress in hemoperfusion adsorbents for common blood toxins (bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea) produced by liver and kidney failure. The composition and structure of various toxin adsorbents, toxin adsorption performance, biocompatibility, blood safety, and the adsorption mechanisms of toxins are discussed. Based on a summary of recent studies, feasible strategies have been explored for designing and preparing hemoperfusion adsorbents to fulfill future development requirements. The trends and clinical application prospects of various toxin adsorbents are also discussed.

Interfacial assembly of chitin/Mn3O4 composite hydrogels as photothermal antibacterial platform for infected wound healing.

To combat bacteria and even biofilm infections, developing alternative antibacterial wound dressings independent of antibiotics is imperative. Herein, this study developed a series of bioactive chitin/Mn3O4 composite hydrogels under mild conditions for infected wound healing application. The in situ synthesized Mn3O4 NPs homogeneously distribute throughout chitin networks and strongly interact with chitin matrix, and as well as endow the chitin/Mn3O4 hydrogels with NIR-assisted outstanding photothermal antibacterial and antibiofilm activities. Meantime, the chitin/Mn3O4 hydrogels exhibit favorable biocompatibility and antioxidant property. Furthermore, the chitin/Mn3O4 hydrogels with the assist of NIR show an excellent skin wound healing performance in a mouse full-thickness S. aureus biofilms-infected wound model, by accelerating the phase transition from inflammation to remodeling. This study broadens the scope for the fabrication of chitin hydrogels with antibacterial property, and offers an excellent alternative for the bacterial-associated wound infection therapy.

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Obstructive jaundice is a common clinical symptom generally caused by bile duct stones, inflammatory hyperplasia, and tumors. It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension, kidney injury, endotoxemia, multiple organ dysfunction syndrome, and even death (Pavlidis and Pavlidis, 2018; Liu et al., 2021). Relieving bile duct obstruction and providing adequate drainage have been considered as the most effective therapies for obstructive jaundice. However, it has not yet been established whether it is beneficial to treat affected patients by pre-operative biliary drainage (Blacker et al., 2021). Moreover, the pathophysiological changes or mechanisms associated with the reversal of organ function following the relief of bile-duct obstruction are unclear (Huang et al., 2004). Therefore, it is necessary to establish an experimental model of reversible obstructive jaundice to simulate biliary drainage in clinical practice.

Polysaccharides based rapid self-crosslinking and wet tissue adhesive hemostatic powders for effective hemostasis.

Hemostatic powders with flexible shape are widely used for the noncompressible and inaccessible hemorrhage wounds. However, current hemostatic powders display poor wet tissue adhesion and fragile mechanical strength of the powder-supported blood clots, leading to compromised hemostasis efficacy. Herein, a bi-component of carboxymethyl chitosan (CMCS) and aldehyde-modified hyaluronic acid grafted with catechol groups (COHA) was designed. Upon absorption of blood, the bi-component powders (CMCS-COHA) spontaneously self-crosslinks into an adhesive hydrogel within 10 s, tightly adhering to wound tissue to form a pressure-resistant physical barrier. During gelation, the hydrogel matrix captures and locks the blood cells/platelets to generate a robust thrombus in the bleeding sites. Compared with traditional hemostatic powder Celox™, CMCS-COHA displays superior blood coagulation and hemostatic performance. More importantly, CMCS-COHA has inherent cytocompatibility and hemocompatibility. These prominent advantages in rapid and effective hemostasis, adaptability to fit irregulate defective wound, easy preservation, facile usage, and bio-safety, make CMCS-COHA a promising hemostatic in emergency situations.

Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.

Synthesis and evaluation of water-soluble imidazolium salt chitin with broad-spectrum antimicrobial activity and excellent biocompatibility for infected wound healing.

Infections caused by bacteria have long constituted a major threat to human health and the economy. Therefore, there is an urgent need to design broad-spectrum antibacterial materials possessing good biocompatibility to treat such infections. Herein, inspired by the good biocompatibility of chitin and antibacterial properties of imidazolium salts, a polysaccharide-based material, imidazolium salt chitin (IMSC), was homogeneously prepared using a facile method with epichlorohydrin as a chemical crosslinker to combine chitin with imidazole to enhance Staphylococcus aureus (S. aureus)-infected wound healing. The characteristics, antimicrobial properties, and biosafety of IMSC were evaluated. The results demonstrated successful grafting of imidazole onto chitin. Furthermore, IMSC exhibited good water solubility, broad-spectrum antimicrobial activity, hemocompatibility, and biocompatibility. Moreover, IMSC enabled complete healing of S. aureus-infected wound in Sprague-Dawley rats within 15 days of application, thus demonstrating that IMSC could reduce wound inflammation and remarkably accelerate wound healing owing to its efficient antibacterial activity and ability to promote collagen deposition in and around the wound area. Therefore, this study provides a promising and potential therapeutic strategy for infected wound healing by synthesizing a water-soluble and broad-spectrum antimicrobial material exhibiting good biocompatibility.

High-strength, antibacterial, antioxidant, hemostatic, and biocompatible chitin/PEGDE-tannic acid hydrogels for wound healing.

Natural polymer hydrogels are widely used in various aspects of biomedical engineering, such as wound repair, owing to their abundance and biosafety. However, the low strength and the lack of function restricted their development and application scope. Herein, we fabricated novel multifunctional chitin/PEGDE-tannic acid (CPT) hydrogels through chemical- and physical-crosslinking strategies, using chitin as the base material, polyethylene glycol diglycidyl ether (PEGDE) and tannic acid (TA) as crosslinking agents, and 90 % ethanol as the regenerative bath. CPT hydrogels maintained a stable three-dimensional porous structure with suitable water contents and excellent biocompatibility. The mechanical properties of hydrogels were greatly improved (tensile stress up to 5.43 ± 1.14 MPa). Moreover, CPT hydrogels had good antibacterial, antioxidant, and hemostatic activities and could substantially promote wound healing in a rat model of full-thickness skin defect by regulating inflammatory responses and promoting collagen deposition and blood vessel formation. Therefore, this work provides a useful strategy to fabricate novel multifunctional CPT hydrogels with excellent mechanical, antibacterial, antioxidant, hemostatic, and biocompatible properties. CPT hydrogels could be promising candidates for wound healing.

Preparation and properties of chitin/silk fibroin biocompatible composite fibers.

In the present world chitin is used enormously in various fields, such as biopharmaceuticals, medical and clinical bioproducts, food packaging, etc. However, its development has been curbed by the impaired performance and cumbersome dissolution process when chitin materials are dissolved and regenerated by physical or chemical methods. To further obtain the regenerated chitin fiber material with improved performance, silk fibroin was introduced into the chitin matrix material, and chitin/silk fibroin biocompatible composite fibers were obtained by formic acid/calcium chloride/ethanol ternary system and top-down wet spinning technology. The produced composite fibers outperformed previously reported chitin-silk composites in terms of the tensile strength (160 MPa) and failure strain (25%). The fibers also performed good cell compatibility and strong cellular affinity for non-toxicity. The cell viabilities of the fibers were about 20% greater than those of silk fiber after three days of co-culture with NIH-3T3. Furthermore, no hemolysis occurs in the presence of chitin/silk fibers, demonstrating their superior hemocompatibility. The fibers had a hemolysis index as low as 1%, which is far lower than the acceptable level of 5%. The material offers prospective opportunities for biomaterial applications in anticoagulation, absorbable surgical sutures, etc.

Rational design of silver NPs-incorporated quaternized chitin nanomicelle with combinational antibacterial capability for infected wound healing.

Bacterial and biofilm infections are prevalent, photothermal antibacterial therapy exploiting Ag NPs was an alternative. However, various matrix materials including polysaccharides used to stabilize Ag NPs are not efficiently utilized. In this study, catechol functionalized quaternized chitin (DQC) is first synthesized, then Ag+ is in situ reduced to small Ag NPs stabilized and well-dispersed by DQC to form Ag NPs-incorporated quaternized chitin (DQCA) nanomicelle in a green and simple way. The photothermal conversion efficiency of the DQCA was up to be 65 %, which was much higher than that of many reported systems. The rationally designed DQCA takes full advantage of each component, specifically, DQCA is endowed with bacterial targeting, sterilization effects of cationic groups and Ag NPs, and superior photothermal combinational bactericidal and antibiofilm activities. The in vitro antibacterial rate of DQCA with NIR laser irradiation was >95 % in 10 min (99.5 % for E. coli and 95.7 % for S. aureus, respectively), and the eradication efficiency against both of the E. coli and S. aureus biofilms reached up to 99.9 %. Moreover, full-thickness S. aureus biofilms-infected wound healing test in the mouse model demonstrates that the combinational effect of DQCA nanomicelle could significantly accelerate the wound healing, by simultaneously reducing inflammation, enhancing re-epithelialization and promoting collagen deposition. And the wound treated with DQCA plus NIR irradiation at day 15 possessed the smallest open wound (2.5 %). Collectively, these features indicate facilely fabricated DQCA nanomicelle gets the most use of each component, and could serve as an excellent alternative for bacterial infection therapy.

Facile fabrication of chitin/ZnO composite hydrogels for infected wound healing.

When ordinary wounds are infected, the skin's self-healing capacity declines; thus appropriate dressings with both antibacterial ability and healing ability for bacteria-associated wounds are indispensable. In this work, multifunctional chitin/ZnO composite hydrogels have been designed as an infected full-thickness skin wound-healing material. The hydrogels are fabricated by a facile one-pot strategy through the sequential addition of commercial ZnO powders into aqueous alkaline chitin solutions, crosslinking and regeneration. The regenerated nanoscale ZnO particles aggregate into microscale particles and are embedded in the chitin matrix with tight interactions, including hydrogen bonding and coordination interactions. The decoration of ZnO endows the chitin/ZnO composite hydrogels with excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with acceptable biocompatibility. More importantly, the chitin/ZnO composite hydrogels show an outstanding accelerated infectious full-thickness wound-healing performance with more fibroblast proliferation, more collagen deposition, and more neogenesis of the epithelium and granulation tissue. Therefore, it is expected that the chitin/ZnO composite hydrogels can serve as competitive skin wound dressings for the prevention and control of infections.

Chitin-glucan composite sponge hemostat with rapid shape-memory from Pleurotus eryngii for puncture wound.

Efficient hemostasis is a great challenge for treating the inaccessible hemorrhage wounds. A novel shape-memory chitin-glucan hemostatic sponge (ATC-Sponge) is constructed via sequentially in-situ removal of protein and glucan from Pleurotus eryngii fruiting body, TEMPO oxidation and Ca2+ crosslinking. The sponge displays interconnected microporous structure with high water absorption and robust mechanical properties. The sponge at dry state shows rapid blood-triggered shape-memory, allowing easy insertion into the puncture wound in a compressed fixed-shape and the subsequent quick volume expansion to conform wound shape to stop bleeding. Compared with standard medical gauze and gelatin sponge, ATC-Sponge demonstrates superior hemostatic performance in the rat femoral artery and non-compressive liver puncture injury models. Additionally, ATC-Sponge can effectively accelerate wound healing. This multi-functional shape-memory ATC-Sponge shows high potential in controlling the bleeding of inaccessible traumas.

Antibacterial and antioxidant chitosan nanoparticles improve the preservation effect for donor kidneys in vitro.

Hypothermic machine perfusion (HMP) is a preferable measure to preserve kidneys from donation after cardiac death (DCD), while the current standard perfusate is imperfect. We synthesized amphiphilic chitosan, N-alkylated-O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (N-alkyl-O-HTCC) as additive in the perfusate, which can self-assembly into micelles in water (size 133 ± 8.48 nm) (ζ-potential 43.9 ± 2.06 mV), with good antibacterial activity for Escherichia coli and Staphylococcus aureus. The derivates can also deliver hydrophobic drug Alda-1 into kidneys through HMP, with drug loading ratio (~42.14%). The delivery system specifically activated mitochondrial acetaldehyde dehydrogenase 2 in kidneys and reduced the ischemic injury. What's more, the addition of N-alkyl-O-HTCC in HMP also activated mitochondria superoxide dismutase 2, presented nice antioxidant activity. These all helped to improve the quality of DCD kidneys. This study provides a feasible amphiphilic carrier for hydrophobic drugs, and provides efficient guidance for perfusate improvement.

Biocompatible Composite Microspheres of Chitin/Ordered Mesoporous Carbon CMK3 for Bilirubin Adsorption and Cell Microcarrier Culture.

Extra bilirubin in the blood can provoke serious illness in patients with severe liver disease. Hemoperfusion is an effective method to remove the extra bilirubin, but its application is limited by the low adsorption efficiency and poor biocompatibility of available adsorbent materials. In this study, chitin/ordered mesoporous carbon CMK3 (Ch/CMK3) microspheres are successfully prepared. Results of characterization experiments indicated that these composite microspheres possess a multilayered porous nanofibrous structure with an extremely large specific surface area (300.19 m2 g-1 ) and large pore size. Notably, the Ch/CMK3 microspheres demonstrated a high bilirubin adsorption capacity (228.19 mg g-1 ) in phosphate buffer solution (PBS), and an outstanding bilirubin removal ratio (76.78% ± 4.40%) in the plasma of rabbits with hyperbilirubinemia without affecting the protein components. More importantly, the Ch/CMK3 microspheres showed no effect on other blood components, no cytotoxicity, and no systemic toxicity to mice. Cell co-culture experiments revealed that the microspheres can provide a 3-dimensional (3D) space to promote cell adhesion, proliferation, and nutrient exchange. These Ch/CMK3 microspheres featuring a strong ability for bilirubin adsorption and good biocompatibility can be a promising candidate in biomedical applications such as hemoperfusion, cell microcarrier, and 3D tissue engineering.

Involvement of Endoplasmic Reticulum Stress-Mediated Activation of C/EBP Homologous Protein in Aortic Regurgitation-Induced Cardiac Remodeling in Mice.

Aortic regurgitation (AR) is a volume overload disease causing eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis is involved in many cardiovascular diseases, but whether they also participate in AR-induced heart failure is still elusive. In this study, we found ER stress activation in myocardial samples from patients with AR. With a unique murine model of AR which induced eccentric cardiac hypertrophy and heart failure, we also found aggravation of cardiac ER stress and apoptosis, as evidenced by a reduction of Bcl-2/Bax ratio and an increase of caspase-3 cleavage. We then examined the signaling effectors involved in ER-initiated apoptosis and found volume overload specifically activated C/EBP homologous protein (CHOP), but not caspase-12 or Jun N-terminal kinase (JNK). Interestingly, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, improved cardiac function, and suppressed ER stress, apoptosis, and CHOP. Furthermore, genetic knockdown of CHOP inhibited cardiac Bcl-2/Bax ratio reduction and caspase-3 activation and rescued cardiac dysfunction. In summary, our findings suggest that ER stress-CHOP signaling is involved in the development of volume overload cardiac hypertrophy induced by AR through promoting cardiomyocytes apoptosis and provide a previously unrecognized target in heart failure induced by volume overload.

Fabrication and characterization of biodegradable KH560 crosslinked chitin hydrogels with high toughness and good biocompatibility.

Chitin hydrogels have multiple advantages of nontoxicity, biocompatibility, biodegradability, and three-dimensional hydrophilic polymer network structure similar to the macromolecular biological tissue. However, the mechanical strength of chitin hydrogels is relatively weak. Construction of chitin hydrogels with high mechanical strength and good biocompatibility is essential for the successful applications in biomedical field. Herein, we developed double crosslinked chitin hydrogels by dissolving chitin in KOH/urea aqueous solution with freezing-thawing process, then using KH560 as cross-linking agent and coagulating in ethanol solution at low temperature. The obtained chitin/ KH560 (CK) hydrogels displayed good transparency and toughness with compressed nanofibrous network and porous structure woven with chitin nanofibers. Moreover, the optimal CK hydrogels exhibited excellent mechanical properties (σb = 1.92 ± 0.21 Mpa; εb = 71 ± 5 %), high swelling ratio, excellent blood compatibility, biocompatibility and biodegradability, which fulfill the requirements of biomedical materials and showing potential applications in biomedicine.

Versatile synthesis, characterization and properties of ß-chitin derivatives from aqueous KOH/urea solution.

Chitin is the second most abundant natural polysaccharide with biocompatibility, biodegradability, and bioactivity. Homogeneous modification of chitin is an efficient way to improve or to impart new properties to chitin. Here, amide-modified ß-chitin (AMC), hydroxyethyl ß-chitin (HEC), and hydroxybutyl ß-chitin (HBC) through Michael addition, Williamson reaction, and ring-opening addition, were homogeneously synthesized from aqueous KOH/urea solution, respectively, with controlled structures and uniform properties. The reactions mainly occur at the hydroxyl groups of C-6 positions of ß-chitin chains due to mild conditions, and the obtained ß-chitin derivatives with high DS values are water-soluble. AMC could transform from sol to gel at acidic condition or upon adding Fe3+ due to the presence of partial carboxylate groups. As a specific highlight, HEC and HBC could thermally form smart hydrogels at physiological temperature, with cytocompatibility and blood biocompatibility, which is very useful as drug/ cell carriers for biomedical applications. The remarkably mild and "green" condition of aqueous KOH/urea solution for the synthesis of chitin derivatives has pioneered a better way to exploit its great diversity of the natural, sustainable polysaccharide.

Highly Efficient and Environmentally Friendly Fabrication of Robust, Programmable, and Biocompatible Anisotropic, All-Cellulose, Wrinkle-Patterned Hydrogels for Cell Alignment.

Wrinkled hydrogels from biomass sources are potential structural biomaterials. However, for biorelated applications, engineering scalable, structure-customized, robust, and biocompatible wrinkled hydrogels with highly oriented nanostructures and controllable intervals is still a challenge. A scalable biomass material, namely cellulose, is reported for customizing anisotropic, all-cellulose, wrinkle-patterned hydrogels (AWHs) through an ultrafast, auxiliary force, acid-induced gradient dual-crosslinking strategy. Direct immersion of a prestretched cellulose alkaline gel in acid and relaxation within seconds allow quick buildup of a consecutive through-thickness modulus gradient with acid-penetration-directed dual-crosslinking, confirmed by visual 3D Raman microscopy imaging, which drives the formation of self-wrinkling structures. Moreover, guided by quantitative mechanics simulations, the structure of AWHs is found to exhibit programmable intervals and aligned nanostructures that differ between ridge and valley regions and can be controlled by tuning the prestretching strain and acid treatment time, and these AWHs successfully induce cell alignment. Thus, a new avenue is opened to fabricate polysaccharide-derived, programmable, anisotropic, wrinkled hydrogels for use as biomedical materials via a bottom-up method.

High-Strength Films Consisted of Oriented Chitosan Nanofibers for Guiding Cell Growth.

Chitosan has biocompatibility and biodegradability; however, the practical use of the bulk chitosan materials is hampered by its poor strength, which can not satisfy the mechanical property requirement of organs. Thus, the construction of highly strong chitosan-based materials has attracted much attention. Herein, the high strength nanofibrous hydrogels and films (CS-E) were fabricated from the chitosan solution in LiOH/KOH/urea aqueous system via a mild regenerating process. Under the mild condition (ethanol at low temperature) without the severe fluctuation in the system, the alkaline-urea shell around the chitosan chains was destroyed, and the naked chitosan molecules had sufficient time for the orderly arrangement in parallel manner to form relatively perfect nanofibers. The nanofibers physically cross-linked to form CS-E hydrogels, which could be easily oriented by drawing to achieve a maximum orientation index of 84%, supported by the scanning electron microscopy and two-dimensional wide-angle X-ray diffraction. The dried CS-E films could be bent and folded arbitrarily to various complex patterns and shapes. The oriented CS-E films displayed even ultrahigh tensile strength (282 MPa), which was 5.6× higher than the chitosan films prepared by the traditional acid dissolving method. The CS-E hydrogels possessed hierarchically porous structure, beneficial to the cell adhesion, transportation of nutrients, and removal of metabolic byproducts. The cell assay results demonstrated that the CS-E hydrogels were no cytotoxicity, and osteoblastic cells could adhere, spread, and proliferate well on their surface. Furthermore, the oriented CS-E hydrogels could regulate the directional growth of osteoblastic cells along the orientation direction, on the basis of the filopodia of the cells to extend and adhere on the nanofibers. This work provided a novel approach to construct the oriented high strength chitosan hydrogels and films.