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Treatment of infected wound by simultaneously eliminating bacteria and inducing angiogenesis to promote wound tissue regeneration remains a clinical challenge. Dynamic and reversable hydrogels can adapt to irregular wound beds, which have raised great attention as wound dressings. Herein, a sprayable chitosan-based hydrogel (HPC/CCS/ODex-IGF1) was developed using hydroxypropyl chitosan (HPC), caffeic acid functionalized chitosan (CCS), oxidized dextran (ODex) to crosslink through the dynamic imine bond, which was pH-responsive to the acidic microenvironment and could controllably release insulin growth factor-1 (IGF1). The HPC/CCS/ODex-IGF1 hydrogels not only showed self-healing, self-adaptable and sprayable properties, but also exhibited excellent antibacterial ability, antioxidant property, low-cytotoxicity and angiogenetic activity. In vivo experiments demonstrated that hydrogels promoted tissue regeneration and healing of bacteria-infected wound with a rate of approximately 98.4 % on day 11 by eliminating bacteria, reducing inflammatory and facilitating angiogenesis, demonstrating its great potential for wound dressing., Competing Interests: Declaration of competing interest The author declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in the paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this present work, a new design for antimicrobial wound bandages is presented. The wound dressings were prepared using cotton fibers reinforced with elastic compression straps and secured with a polyester fabric of tight mesh size. The cotton pads were doped with a wound healing biocomposite, composed of chitosan, glycogen, and ZnO nanoparticles (CG@ZnONPs) previously formulated through a green process. The size of ZnONPs in the prepared CG@ZnONPs was 30-80 nm. The cotton pads impregnated with the CG@ZnONPs nanocomposite were characterized using FTIR, SEM, EDX, TGA, and DTGA methods. Moreover, the prepared dressings were tested on a number of intentionally injured rats. In this experiment, the % contraction of the treated wounds was monitored and compared to that of a control group of wounded rats, to which only sterile gauzes were applied. The results showed a much faster and an almost complete healing of rats treated with the synthesized dressings and the results were further confirmed by histopathological examination. The dressings were also found to exert a significant antimicrobial activity against a number of pathogenic microorganisms, generally encountered in common wounds, and could therefore be recommended to be a novel biomedical application for a fast, successful, and flawless wounds healing process., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Excessive bleeding in traumatic hemorrhage is the primary concern for natural wound healing and the main reason for trauma deaths. The three-dimensional (3D) bioprinting of bioinks offers the desired structural complexity vital for hemostasis activity and targeted cell proliferation in rapid and controlled wound healing. However, it is challenging to develop suitable bioinks to fabricate specific 3D scaffolds desirable in wound healing. In this work, a 3D composite scaffold is designed using bioprinting technology and synergistic hemostasis mechanisms of cellulose nanofibrils (TCNFs), chitosan, and casein to control blood loss in traumatic hemorrhage. Bioinks that consist of casein bioconjugated TCNF (with a casein content of 104.5 ± 34.1 mg/g) using the carbodiimide cross-linker chemistry were subjected to bioprinting for customizable 3D scaffold fabrication. Further, the 3D composite scaffolds were in situ cross-linked using a green ionic complexation approach. The covalent conjugation among TCNF, casein, and chitosan was confirmed by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and X-ray diffraction (XRD) studies. The in vitro hemostasis activity of the 3D composite scaffold was analyzed by a human thrombin-antithrombin (TAT) assay and adsorption of red blood cells (RBCs) and platelets. The 3D composite scaffold had a better swelling behavior and a faster whole blood clotting rate at each time point than the 3D TCNF scaffold and commercial cellulose-based dressings. The TAT assay demonstrated that the 3D composite scaffold could form a higher content of thrombin (663.29 pg/mL) and stable blood clot compared to a cellulosic pad (580.35 pg/mL), 3D TCNF (457.78 pg/mL), and cellulosic gauze (328.92 pg/mL), which are essential for faster blood coagulation. In addition, the 3D composite scaffold had a lower blood clotting index (23.34%) than the 3D TCNF scaffold (41.93%), suggesting higher efficiencies for RBC entrapping to induce blood clotting. The in vivo cytocompatibility was evaluated by a 3D cell culture study, and results showed that the 3D composite scaffold could promote growth and proliferation of NIH 3T3 fibroblast cells, which is vital for wound healing. Cellulase-based in vitro deconstruction of the 3D composite scaffold showed significant weight loss (80 ± 5%) compared to the lysozyme hydrolysis (22 ± 5%) after 28 days of incubation, suggesting the biodegradation potential of the composite scaffold. In conclusion, this study proposes efficient prospects to develop a 3D composite scaffold from bioprinting of TCNF-based bioinks that can accelerate blood clotting and wound healing, suggesting its potential application in reducing blood loss during traumatic hemorrhage.

Bio sustainable hydrogels including tunable morphological and/or chemical cues currently offer a valid strategy of designing innovative systems to enhance healing/regeneration processes of damaged tissue areas. In this work, TEMPO-oxidized cellulose nanofibrils (T-CNFs) were embedded in alginate (Alg) and polyvinyl alcohol (PVA) solution to form a stable mineralized hydrogel. A calcium chloride reaction was optimized to trigger a crosslinking reaction of polymer chains and mutually promote in situ mineralization of calcium phosphates. FTIR, XRD, SEM/EDAX, and TEM were assessed to investigate the morphological, chemical, and physical properties of different mineralized hybrid hydrogels, confirming differences in the deposited crystalline nanostructures, i.e., dicalcium phosphate dehydrate (DCPDH) and hydroxyapatite, respectively, as a function of applied pH conditions (i.e., pH 4 or 8). Moreover, in vitro tests, in the presence of HFB-4 and HSF skin cells, confirmed a low cytotoxicity of the mineralized hybrid hydrogels, and also highlighted a significant increase in cell viability via MTT tests, preferentially, for the low concentration, crosslinked Alg/PVA/calcium phosphate hybrid materials (<1 mg/mL) in the presence of hydroxyapatite. These preliminary results suggest a promising use of mineralized hybrid hydrogels based on Alg/PVA/T-CNFs for bone and wound healing applications.

Hydrogel dressings with similar structural characteristics to the extracellular matrix and tunable physicochemical properties have become promising candidates for wound healing. However, the fabrication of an ideal hydrogel dressing with low-cost, good biocompatibility, excellent hemostatic capacity, potent and broad-spectrum antibacterial activity remains a huge challenge. Herein, a lignocellulose-based nanocomposite hydrogel (ATC/SA/PVA) is fabricated by simply mixing Ag nanoparticles loaded, tannic acid-decorated lignocellulose nanofibrils with sodium alginate and polyvinyl alcohol. Based on the dynamic borate ester bonds and multiple weak hydrogen bonds, the fabricated hydrogel exhibits excellent flexibility and self-healing performance. Its highly porous structure endows the gel excellent blood and tissue exudates absorption ability. Interestingly, the release behavior of Ag nanoparticles from hydrogel displays pH dependence, which can facilitate the accumulation of Ag nanoparticles at the wound site, thereby accelerating the process of wound healing. In vitro antibacterial assay demonstrates the potent antibacterial ability of hydrogel against both Gram-positive (S. aureus) and negative bacteria (E. coli). More importantly, in vivo investigations reveal that such hydrogel can effectively accelerate tissue regeneration and wound healing with no obvious adverse effects. All these results suggest that this nanocomposite hydrogel would be a promising candidate to accelerate wound healing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nature provides rich bionic resources for the construction of advanced materials with excellent mechanical properties. In this work, inspired by animal tendons, a bionic collagen fiber was developed using collagen liquid crystals as the pre-oriented bioink. The texture of liquid crystalline collagen observed from polarized optical microscopy (POM) showed the specific molecular pre-orientation. Meanwhile, the collagen spinning liquids exhibited a minimal rise in viscosity upon increasing concentration from 60 to 120 mg/mL, indicating the feasible processability. The collagen fiber, which was prepared via wet spinning without being denatured, exhibited the favorable orientation of fibrils along its axis as observed with FESEM and AFM. Thanks to the synergistic effects between pre-orientation and shearing orientation, the maximum tensile strength and Young's modulus of collagen fibers reached 9.98 cN/tex (219.29 ± 22.92 MPa) and 43.95 ± 1.11 cN/tex (966.20 ± 24.30 MPa), respectively, which were also analogous to those of tendon. In addition, the collagen fiber possessed a desirable wet strength. Benefiting from the natural tissue affinity of collagen, the as-prepared bionic collagen fiber possessed excellent wound suture performance and biodegradability in vivo, which offers a new perspective for the potential of widespread applications of collagen fibers in biomedical fields., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The effectiveness of tannic acid as antimicrobial and wound healing for burns have been shown for a century; however, uncontrolled target dosage may result in undesirable side-effects. Remarkably, tannic acid polyphenols compounds crosslinked with polymeric materials produce a strong composite containing the beneficial properties of this tannin. However, investigation of the crosslink structure and its antibacterial and regenerative properties are still unknown when using nanocellulose by mechanical defibrillation; additionally, due to the potential crosslink structure with chitosan, its structure can be complex. Therefore, this work uses bleach kraft nanocellulose in order to investigate the effect on the physical and regenerative properties when incorporated with chitosan and tannic acid. This film results in increased rigidity with a lamellar structure when incorporated with tannic acid due to its strong hydrogen bonding. The release of tannic acid varied depending on the structure it was synthesised with, whereas with chitosan it presented good release model compared to pure cellulose. In addition, exhibiting similar thermal stability as pure cellulose films with antibacterial properties tested against S. aureus and E. coli with good metabolic cellular viability while also inhibiting NF-κB activity, a characteristic of tannic acid.

Electro-conductive hydrogel (ECH) with self-healing, shape memory and biocompatible properties is highly urgent for wearable strain sensors to prolonging their lifespan, endowing programmable shape control property, and improving affinity to skin during service. However, most of synthetic polymer-based ECH usually involve potential toxicity, long healing and shape drive time. Herein, a fast healable and shape memory ECH with excellent biocompatibility is reported for the first time by incorporating cellulose nanocrystals grafted phenylboronic acid (CNCs-ABA) and multiwalled carbon nanotubes (MWCNTs) into polyvinyl alcohol (PVA). CNCs-ABA is designed as dispersant and crosslinker in hydrogel. pH-induced dynamic borate bonds give hydrogel excellent shape recovery and fixity ratio of 82.1% and 78.2%, respectively. Meanwhile, 97.1% healing efficiency is obtained within 2 min depending on remarkable photothermal effect of MWCNTs and reversible microcrystallization. Double crosslinking networks endow excellent mechanical properties to hydrogel, whose tensile strength, strain and elastic modulus reach 227.0 kPa, 395.0% and 9.0 kPa, respectively. Furthermore, the synergistic effect of MWCNTs and NaOH enhance the conductivity of hydrogel with value of 3.8×10 -2  S/m. In addition, the hydrogel can act as strain sensor for detecting human motion with superior biocompatibility and fast resistance response to applied strain, which is suitable for human health management., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, a carboxyl-modified cellulosic hydrogel was developed as the base material for wound dressings. ε-poly-l-lysine, a natural polyamide, was then covalently linked to the hydrogel through a bioconjugation reaction, which was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR). The antibacterial efficacy of the hydrogel was tested against two model bacteria, Staphylococcus aureus and Pseudomonas aeruginosa , two of the most commonly found bacteria in wound infections. Bacterial viability and biofilm formation after exposure of bacteria to the hydrogels were used as efficacy indicators. Live/Dead assay was used to measure the number of compromised bacteria using a confocal laser scanning microscope. The results show that the antibacterial hydrogel was able to kill approximately 99% of the exposed bacteria after 3 h of exposure. In addition, NIH/3T3 fibroblasts were used to study the biocompatibility of the developed hydrogels. Water-soluble tetrazolium salt (WST)-1 assay was used to measure the metabolic activity of the cells and Live/Dead assay was used to measure the viability of the cells after 24, 48, and 72 h. The developed antibacterial hydrogels are light weight, have a high water-uptake capacity, and show high biocompatibility with the model mammalian cells, which make them a promising candidate to be used for wound dressing applications.

In this study, a versatile cellulose conductive hydrogels with outstanding mechanical properties, rapid self-healing performance, and excellent thermal sensitivity were successfully fabricated. The tensile strength and toughness of the gels gradually increased to 249 kPa and 1.57 MJ/m 3 , respectively, and the healing efficiency of the hydrogels quickly reached 96.3% within 60 min. Importantly, the hydrogels exhibited a broad strain window (0-2066%) with a gauge factor ranging from 0.22 to 6.7, which could monitor of both obvious and subtle motion of the human body with high sensitivity and good repeatability. Moreover, the sensors also possessed good thermal sensitivity in the 0% and 400% state, and the response of the gel sensors increased from 8.3 to 87.9 when the temperature was increased from 35 to 85 °C. This study provides inspiration for the development of biocompatible and multifunctional cellulose-based wearable sensors with excellent mechanical, strain and temperature sensing and self-healing properties., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The present study describes the impregnation of coffee extract (CE) into bacterial cellulose synthesized from kombucha tea fungus (KBC) of different cellulose content, incubated for different incubation periods (2, 4, and 10 days), to prepare biocomposites having the potential for wound healing applications. Total polyphenols in hydroalcoholic extracts from ground roasted coffee and its release from the prepared biocomposites were determined as gallic acid equivalent. The polyphenols content was found to be 13.66 mg/g and the minimum inhibitory concentration (MIC) of the CE was determined using colony-forming unit (CFU) method against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus where the growth inhibition was 86 and 97% respectively. Biocomposites (KBC/CE) with the lowest cellulose and CE content showed the highest wet tensile stress (3.35 MPa), absorption of pseudo extracellular fluid (154.32% ± 4.84), and water vapor transmission rate (3184.94 ± 198.07 g/m 2 /day), whereas it showed the lowest polyphenols' release (51.85% ± 2.94)when immersed in PBS buffer of pH 7.4. The impregnation of CE into KBC provided biocomposites that can enlarge the range of BC in the biomedical application.

Background: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects., Patients and Methods: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken. The differences in gene expression associated with angiogenic processes in specimens obtained from ischaemic and non-ischaemic skeletal muscle were confirmed by quantitative real-time polymerase chain reaction (PCR) analysis., Results: Compared with non-ischaemic skeletal muscle biopsy of chronic-ischaemic skeletal muscle contained 55 significantly up-regulated and 45 down-regulated genes, out of which 64 genes had a known genetic product. Tissue samples of ischaemic muscle were characterized by increased expression of cell survival factors (e. g. tissue factor pathway inhibitor 2) in combination with reduced expression of cell proliferation effectors (e. g. microfibrillar-associated protein 5 and transferrin receptor). The expression of growth factors (e. g. early growth response 3 and chemokine receptor chemokine C-X-C motif ligand 4) which play a central role in arterial and angiogenic processes and anti-angiogenetic factors (e. g. pentraxin 3) were increased in chronic ischaemic skeletal muscle. An increased expression of extracellular matrix proteins (e. g. cysteine-rich angiogenic inducer 61) was also observed., Conclusions: Gene expression profiles in biopsies of gastrocnemius muscle in patients with chronic critical limb ischaemia showed an increase in pro-survival factors, extracellular matrix protein deposition, and impaired proliferation, compared with non-ischaemic controls. Further studies are required to analyse the endogenous repair mechanism.

Nanocellulose has a variety of advantages, which make the material most suitable for use in biomedical devices such as wound dressings. The material is strong, allows for production of transparent films, provides a moist wound healing environment, and can form elastic gels with bioresponsive characteristics. In this study, we explore the application of nanocellulose as a bioink for modifying film surfaces by a bioprinting process. Two different nanocelluloses were used, prepared with TEMPO mediated oxidation and a combination of carboxymethylation and periodate oxidation. The combination of carboxymethylation and periodate oxidation produced a homogeneous material with short nanofibrils, having widths <20 nm and lengths <200 nm. The small dimensions of the nanofibrils reduced the viscosity of the nanocellulose, thus yielding a material with good rheological properties for use as a bioink. The nanocellulose bioink was thus used for printing 3D porous structures, which is exemplified in this study. We also demonstrated that both nanocelluloses did not support bacterial growth, which is an interesting property of these novel materials.