Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing

A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague–Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing.     

In-situ forming biodegradable glycol chitosan-based hydrogels: Synthesis,characterization, and chondrocyte culture

In-situ forming hydrogels from thiolated glycol chitosan (GCH-SH) and vinyl sulfone-modified PEG (PL-VS) were designed, prepared and successfully applied as biodegradable, non-toxic bio-scaffolds for chondrocyte culture. The hydrogels could be formed in situ under physiological conditions via Michael-type addition between the GCH-SH and PL-VS at a low polymer concentration of 1–3% (w/v). Gelation times varied from 0.75 to 50 min, depending on the polymer concentration and the arm number of PEG-VS. Moreover, a high arm number and a high polymer concentration may lead to efficient network formation of GCH-SH/PEG-VS hydrogels. These hydrogels were found biodegradable in the presence of lysozyme, a cationic protein in the body, for a long period of time. Rheological studies indicated that these hydrogels generally displayed highly elastic property and had higher mechanical strength than those from thiolated hyaluronic acid/PEG-VS reported previously. SEM observation revealed that these hydrogels possessed well-interconnected microporous morphology. Besides these, the chondrocytes could be incorporated and homogeneously distributed in the hydrogel based on GCH-SH and 4-arm PL-VS. Importantly, after cell culture of 14 days, the chondrocytes in the hydrogel remained viable, as determined by a live–dead assay, and the cells kept their round chondrocytic phenotype. These results suggest that Michael-type addition is an effective method in the preparation of in-situ forming, biodegradable GCH-based hydrogels serving as bio-scaffolds for chondrocyte culture.     

X-ray computed tomography proof of bacterial-based self-healing in concrete

Self-healing strategies are regarded as a promising solution to reduce the high maintenance and repair cost of concrete infrastructures. In the present work, a bacterial-based self-healing by use of hydrogel encapsulated bacterial spores (bio-hydrogels) was investigated. The crack closure behavior of the specimens with/without bio-hydrogels was studied quantitatively by light microscopy. To have a view of the self-healing inside the specimens, a high resolution X-ray computed microtomography (X-ray μCT) was used. The total amount and the distribution of the healing products in the whole matrix were investigated. This study indicates that the specimens incorporated with bio-hydrogels had distinct improved healing efficiency compared to the reference ones with pure hydrogel only. The healing ratios in the specimens with bio-hydrogels were in the range from 70% to 100% for the cracks smaller than 0.3 mm, which is more than 50% higher than for the ones with pure hydrogel; and the maximum crack bridging was about 0.5 mm (in 7 d), while pure hydrogels only allowed healing of cracks of about 0.18 mm. The total volume ratio of the healing product in the specimens with bio-hydrogels amounted to 2.2%, which was about 60% higher than for the ones with pure hydrogel (1.37%).     

Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment

The aims of this study were to find the optimal formulation for the preparation of metronidazole-loaded chitosan microparticles (MTZ-MPs) via an emulsion cross-linking process, and to compare the in vitro release of MTZ from hydrogels and films containing the drug in forms of MTZ-MPs and raw powders. The effects of emulsifier type and concentration, amount of cross-linking agent, cross-linking time, drug:chitosan ratio, form of drug adding and washing method on the properties of the MTZ-MPs were investigated. The results indicated that the optimal conditions for round and free-flowing MTZ-MPs with a high percentage of entrapped drug and preferable release profile were 1% of Span80 in soybean oil, 5% of glutaraldehyde based on chitosan solution, 30 min of cross-linking time, 1:1 drug:chitosan ratio, drug adding in form of ethanol solution and washing with hexane only. MTZ-MPs prepared from the optimal formulation were incorporated in mucoadhesive hydrogel and film. The release profiles of the drug from hydrogel and film containing MTZ-MPs were in prolong pattern compared with those containing drug powders. However, the hydrogels exhibited higher preferable pattern of release profile than the films. Therefore, the hydrogel containing MTZ-MPs was possible to be further clinically investigated for peridontitis treatment.     

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full‐Thickness Skin Regeneration During Wound Healing

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full‐thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid‐graft‐dopamine and reduced graphene oxide (rGO) using a H₂O₂/HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self‐healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full‐thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full‐thickness skin repair.     

Release of Ftorafur from pH-sensitive hydrogels with hyperbranched poly(4-vinylbenzyl chloride) moieties

Drug release behavior of a hydrogel is related to its transport mechanism, which is dominated by structure of the hydrogel. Therefore, we prepared pH-sensitive poly(4-vinylpyridine) (P4VP) hydrogels with hyperbranched poly(4-vinylbenzyl chloride) (PVBC; M_n = 2391 g/mol, PDI = 1.87, the minimum percent linearity = 12.4%) moieties (P4VP-PVBC) by atom transfer radical polymerizations (ATRP) in two steps. A PVBC moiety provides the hydrogel with a microenvironment, which may encapsulate guest molecules like drug. The presence of the microenvironment could affect drug transport in the hydrogel matrices. To understand this, we used Ftorafur as drug molecule, and investigated release behavior of the P4VP-based hydrogels. Diffusion and transport mechanism of Ftorafur in the P4VP-based hydrogels was analyzed by early-time and late-time approximation diffusion coefficients. It was found that the transport behavior of Ftorafur was related to the presence of the PVBC moiety and external pH. The presence of the PVBC moiety could sustain release of Ftorafur.     

Injectable melatonin-loaded carboxymethyl chitosan (CMCS)-based hydrogel accelerates wound healing by reducing inflammation and promoting angiogenesis and collagen deposition

Carboxymethyl chitosan(CMCS)-based hydrogels have antibacterial activity,and have shown the abilities of preventing wound infection,promoting cell proliferation,accelerating collagen deposition,and stimulating hyaluronic acid formation during wound healing.As a hormone produced by the pineal gland in humans and animals,melatonin promotes skin wound healing by regulating the release of inflammatory mediators and accelerating the proliferation and migration of cells,angiogenesis,and collagen deposition.However,the combined effects of CMCS and melatonin on wound healing remain unclear.Injectable CMCS-based hydrogels containing melatonin were prepared,and their healing effects were evaluated using a full-thickness cutaneous wound model in rats.Compared with the control and the hydrogel with no melatonin groups,the melatonin-loaded hydrogel significantly increased the percentage of wound closure,promoted the proliferation of granulation tissue and re-epithelialization,and accelerated collagen deposition.Additionally,the melatonin-loaded hydrogel promoted angiogenesis and vascular endothelial growth factor receptor protein expression and increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase.The melatonin-loaded hydrogel also markedly increased the expression of collagen III,α-smooth muscle actin,and transforming growth factor-β1 proteins and reduced collagen I expression.These results suggest that the melatonin-loaded hydrogel promoted granulation tissue formation and accelerated wound healing by reducing inflammation and promoting angiogenesis and collagen deposition.     

Thermosensitive in situ-forming dextran–pluronic hydrogels through Michael addition

A thiolated dextran (Dex-SH) with a degree of substitution of 10 was synthesized and used for in situ hydrogel formation via Michael-type addition using vinyl sulfone functionalized Pluronic 127 (PL-VS) or acrylated Pluronic 127 (PL-Ar). Dextran/Pluronic hydrogels were rapidly formed in situ under physiological conditions upon mixing the solutions of Dex-SH and PL-VS or PL-Ar at a PL concentration of 10 or 20 w/v%. Rheological studies showed that these hydrogels with a broad range of storage moduli of 0.3 to 80 kPa could be obtained by varying PL concentration from 5% to 20 w/v%. Moreover, the hydrogels at a PL concentration of 10% or 20 w/v% revealed thermosensitive property with a temperature increase from 10 to 37 °C. Dex-SH/PL-Ar hydrogels were degradable under physiological conditions and had lower cytotoxicity than Dex-SH/PL-VS hydrogels. These thermosensitive injectable hydrogels show promise for biomedical applications.     

Temperature-sensitivity and cell biocompatibility of freeze-dried nanocomposite hydrogels incorporated with biodegradable PHBV

The structure, morphology, thermal behaviors and cytotoxicity of novel hydrogels, composed of poly(N-isopropylacrylamide)(PNIPAM) and biodegradable polyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) under nanoclay hectorite “Laponite XLG” severed as physical cross-linker, were characterized by X-ray diffraction, scanning electron microscopy, gravimetric method, differential scanning calorimetry, and cell culture experiments. It was found that, due to the introduction of hydrophobic PHBV, the homogeneity of interior pore in the pure PNIPAM nanocomposite hydrogel was disrupted, the transparency and swelling degree gradually decreased. Although the weight ratio between PHBV and NIPAM increased from 5 to 40 wt.%, the volume phase transition temperature (VPTTs) of hydrogel were not altered compared with the pure PNIPAM nanocomposite hydrogel. No matter what PHBV content, the PHBV/PNIPAM/Hectorite hydrogels always exhibit good stimuli-responsibility. In addition, human hepatoma cells(HepG2) adhesion and spreading on the surface of PHBV-based hydrogels was greatly improved than that of pure PNIPAM nanocomposite hydrogel at 37 °C due to the introduction of PHBV.     

Hydrogels from silk fibroin metastable solution: Formation and characterization from a biomaterial perspective

Silk fibroin (SF) hydrogels were obtained from the dialysis of a SF metastable solution. Temperature and calcium concentration in SF solution/hydrogel were measured, as critical variables for SF gelation phenomenon. Gelation time of SF solution was increased by decreasing the dialysis temperature, whereas the residual calcium concentration was higher when higher dialysis temperatures were applied. Hydrogels obtained at 20 °C were characterized after freeze-drying. SEM micrographs showed porous structures, of ca. 20 μm (in cross-sectional area) and 5 μm (on surface). XRD indicated the presence of a β-sheet structure that is formed during SF gelation. In hydrogel formation, SF molecules in solution are dehydrated and interact by intra and intermolecular hydrogen bonds, forming a stable hydrogel. DSC measurements showed the decomposition peak for SF at 290 °C, characteristic of SF β-sheet structure, which is in accordance with the XRD results and demonstrate its high thermal resistance. SF hydrogels were found not to be toxic to cells using in vitro cytotoxicity tests. Results indicate that silk fibroin hydrogels hold promise for use in the biomaterial field.     

Recognition of four structurally resembled benzoic acid derivatives by albumin-crosslinked poly(acrylamide) hydrogel

Poly(acrylamide) hydrogels crosslinked by bovine serum albumin (BSA) were prepared by the introduction of vinyl groups into BSA and subsequent co-polymerization with acrylamide (AAm). The hydrogels were loaded with four structurally resembled benzoic acid derivatives such as salicylic acid, o-anisic acid, salicylamide and sodium benzoate, and their release from the hydrogel was investigated. The affinity of these four compounds for BSA gradually decreased in a following order; salicylic acid > o-anisic acid > salicylamide > sodium benzoate. The amounts of compounds loaded on a hydrogel of high BSA content and the duration of their release were found to be dependent on the affinity for BSA clearly reflecting the subtle difference in BSA affinity of each compound. Therefore, this hydrogel would be used not only as a sustained drug release carrier, but also a facile tool to evaluate the binding of various compounds to serum albumin.     

Co-electrospun blends of PU and PEG as potential biocompatible scaffolds for small-diameter vascular tissue engineering

A small-diameter vascular graft (inner diameter 4 mm) was fabricated from polyurethane (PU) and poly(ethylene glycol) (PEG) solutions by blend electrospinning technology. The fiber diameter decreased from 1023 ± 185 nm to 394 ± 106 nm with the increasing content of PEG in electrospinning solutions. The hybrid PU/PEG scaffolds showed randomly nanofibrous morphology, high porosity and well-interconnected porous structure. The hydrophilicity of these scaffolds had been improved significantly with the increasing contents of PEG. The mechanical properties of electrospun hybrid PU/PEG scaffolds were obviously different from that of PU scaffold, which was caused by plasticizing or hardening effect imparted by PEG composition. Under hydrated state, the hybrid PU/PEG scaffolds demonstrated low mechanical performance due to the hydrophilic property of materials. Compared with dry PU/PEG scaffolds with the same content of PEG, the tensile strength and elastic modulus of hydrated PU/PEG scaffolds decreased significantly, while the elongation at break increased. The hybrid PU/PEG scaffolds demonstrated a lower possibility of thrombi formation than blank PU scaffold in platelet adhesion test. The hemolysis assay illustrated that all scaffolds could act as blood contacting materials. To investigate further in vitro cytocompatibility, HUVECs were seeded on the scaffolds and cultured over 14 days. The cells could attach and proliferate well on the hybrid scaffolds than blank PU scaffold, and form a cell monolayer fully covering on the PU/PEG (80/20) hybrid scaffold surface. The results demonstrated that the electrospun hybrid PU/PEG tubular scaffolds possessed the special capacity with excellent hemocompatibility while simultaneously supporting extensive endothelialization with the 20 and 30% content of PEG in hybrid scaffolds.     

Preparation and characterization of pH- and temperature-responsive nanocomposite double network hydrogels

A methodology is described for the preparation of pH- and temperature-responsive double network (DN) hydrogels with poly(N-isopropylacrylamide) (PNIPAM) as a tightly crosslinked 1st network, polyacrylic acid (PAA) as a loosely crosslinked 2nd network and graphene oxide (GO) as an additive. GO sheets were first prepared via an oxidation reaction and then dispersed in NIPAM aqueous solution via silanization. Free-radical polymerization of NIPAM was carried out at 20 °C in a water bath, and then subjected to UV light, leading to the formation of pH- and temperature-responsive PNIPAM/AA/GO DN hydrogels. The effects of GO sheets and AA contents on various physical properties were investigated. Results show that PNIPAM/AA/GO hydrogels undergo a large volumetric change in response to temperature. It also exhibits significantly fast swelling/deswelling compared with conventional PNIPAM hydrogel. Moreover, the PNIPAM/AA/GO hydrogels have a much better mechanical property than the conventional PNIPAM hydrogels.     

The influence of operating parameters on the drug release and anti-bacterial performances of alginate wound dressings prepared by three-dimensional plotting

Three-dimensional plotting was used to manufacture fibrous alginate hydrogel wound dressings. Samples manufactured using varied operating parameters (increased air pressure, nozzle diameter, and layer increment or decreased calcium concentration, alginate concentration, and speed of the nozzle in the x and y directions) were compared to the control samples. The changes in the fiber size, porosity, tensile properties, degradation, swelling ratio, tetracycline release efficacy, water vapor transmission rate (WVTR), and bacterial inhibition potential due to alterations of the operating parameters were measured. The samples manufactured using altered operating parameters had larger fiber sizes and were less porous than the controls (p < 0.05). A significantly higher Young's modulus, a larger ultimate tensile strength, less degradation, and lower swelling ratios were also found among some of the altered samples (p < 0.05). The tetracycline release efficacies and bacterial inhibition potentials of the altered samples were not found to be significantly different from those of the controls. The WVTRs of most samples were slightly lower than those of common commercial dressings. When compared to films, the fibrous samples were able to absorb liquid faster and were less stiff, allowing for better conformation to the contours of the wounds. The fibrous samples also provided more sustained tetracycline release.     

Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples.     

Characterization of surface charge and mechanical properties of chitosan/alginate based biomaterials

This study aims to examine mechanical properties and surface charge characteristics of chitosan/alginate-based films for biomedical applications. By varying the concentrations of chitosan and alginate, we have developed films with varying surface charge densities and mechanical characteristics. The surface charge densities of these films were determined by applying an analytical model on force curves derived from an atomic force microscope (AFM). The average surface charge densities of films containing 60% chitosan and 80% chitosan were found to be ? 0.46 mC/m² and ? 0.32 mC/m², respectively. The surface charge density of 90% chitosan containing films was found to be neutral. The elastic moduli and the water content were found to be decreasing with increasing chitosan concentration. The films with 60%, 80% and 90% chitosan gained 93.5 ± 6.6%, 217.1 ± 22.1% and 396.8 ± 67.5% of their initial weight, respectively. Their elastic moduli were found to be 2.6 ± 0.14 MPa, 1.9 ± 0.27 MPa and 0.93 ± 0.12 MPa, respectively. The trend observed in the mechanical response of these films has been attributed to the combined effect of the concentration of polyelectrolyte complexes (PEC) and the amount of water absorbed. The Fourier transform infrared spectroscopy experiments indicate the presence of higher alginate on the surface of the films compared to the bulk in all films. The presence of higher alginate on surface is consistent with negative surface charge densities of these films, determined from AFM experiments.     

Development and characterization of Poly (vinyl alcohol) based hydrogels for potential use as an articular cartilage replacement

Hydroxyapatite (HA) reinforced Poly(vinyl alcohol) (PVA) hydrogel composites has been proposed as a promising biomaterial to replace diseased or damaged articular cartilage. Here, PVA/in-situ produced HA hydrogels with 0, 3 and 7.5 wt.% of HA content were obtained by freezing/thawing technique. Thermal, structural and mechanical characterizations were carried out. SEM micrographs revealed that HA was homogeneously distributed in PVA until 3 wt.% whereas partial agglomeration was observed for higher contents (7.5 wt.%). No significant changes were observed in the glass transition temperature (the average value was near to 78 °C ± 3 °C), the melting point and structural water content whereas the gel fraction slightly increased (from 0.72 to 0.78) with the increase the content of HA. The absorbed water decreased (from 85.7% to 80.5%) as a function of HA content The stress–strain curves were really different in hydrated and non-hydrated conditions, changing from non-linear, in presence of water, to linear behavior in a dried state, being in the first case consistent with the articular cartilage . The lowest friction coefficient was obtained for samples with 3 wt. % HA (0.067 ± 0.049), which is, together with a high resistance (721 ± 25 kPa), an important property for materials that will be used as articular replacement. The results indicate that this hydrogel could be used, after other studies, as articular cartilage replacement.     

Active ingredient-containing chitosan/polycaprolactone nonwoven mats: Characterizations and their functional assays

This study demonstrates a facile method developed to generate a chitosan/polycaprolactone (CS/PCL) nonwoven mat. All nonwoven mats are composed of microfibers with an average diameter of 2.51 ± 0.69 μm. The X-ray photoelectron spectroscopy data indicate that positively charged nitrogen was generated on the surface of the mats after undergoing CS coating. By using a non-contacting electrostatic voltmeter, we determined that the nonwoven mats exhibited a positive potential and the charge density of the CS/PCL nonwoven mat was in proportion to the thickness of the CS overlayer. Moreover, platelet aggregation and anti-bacterial ability were enhanced by the CS/PCL nonwoven mat as compared to that of PCL nonwoven mat alone. The enhancements of the CS/PCL nonwoven mat on platelet aggregation are further promoted by incorporating a 1 mM calcium ion in its CS overlayer. We also find that the addition of tea tree oil in the CS overlayer significantly inhibited LPS-induced nitrite formation in Raw 264.7 macrophages. In conclusion, our CS/PCL nonwoven mat possesses pharmacological effects including an increase of platelet aggregation, anti-bacterial, anti-adhesive, and anti-inflammatory activities. The performance of this CS/PCL nonwoven mat can be further promoted by incorporating active compounds to exert therapeutic effects in wound healing.     

Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition

Polyethylene glycol-maleimide modified ε-polylysine (EPL-PEG-MAL) with a unique comb-shaped structure was designed and used as a novel crosslinker for thiolated chitosan (CSS). Novel polysaccharide/polypeptide bionic hydrogels based on CSS and EPL-PEG-MAL could form rapidly in situ within 1 min via Michael addition under physiological conditions. Rheological studies showed that introduction of PEG can dramatically improve the storage modulus (G′) of the hydrogels and the optimal hydrogel system showed superior G′ of 1,614 Pa. The maximum adhesion strength reached 148 kPa, six times higher than that of fibrin glue. Cytotoxicity test indicated that the hydrogel is nontoxic toward growth of L929 cells. Gelation time, swelling ratio, storage modulus and adhesion strength of the hydrogels can be modulated by the content of PEG-maleimide, CSS concentration and molar ratio of maleimide group to thiol group. Benefiting from the fast gelation behaviors, desirable mechanical properties, relatively high adhesive performance and no cytotoxicity, these hydrogels have the potential applications as promising biomaterials for tissue adhesion and sealing.     

Cross-linked nanocomposite hydrogels based on cellulose nanocrystals and PVA: Mechanical properties and creep recovery

Cellulose nanocrystal (CNC) reinforced poly(vinyl alcohol) (PVA) hydrogels with a water content of ∼92% were successfully prepared with glutaraldehyde (GA) as a cross-linker. The effects of the CNC content on the thermal stability, swelling ratio and mechanical and viscoelastic properties of the cross-linked hydrogels were investigated. The compressive strength at 60% strain for the hydrogels with 1 wt% CNCs increased by 303%, from 17.5 kPa to 53 kPa. The creep results showed that the addition of CNCs decreased the creep elasticity due to molecular chain restriction. The almost complete strain recovery (∼97%) after fixed load removal for 15 min was observed from the hydrogels with CNCs, compared with 92% strain recovery of the neat cross-linked PVA hydrogels. The incorporation of CNCs did not affect the swelling ratio and thermal stability of the hydrogels. These results suggest the cross-linked CNC-PVA hydrogels have potential for use in biomedical and tissue engineering applications.