Hemocompatibility of Ca2+‐Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis

The present work investigates Ca²⁺‐crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood‐derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet‐free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.     

Synthesis and rheological investigation of self‐healable deferoxamine grafted alginate hydrogel

Deferoxamine grafted alginate (SA‐DFA) was successfully synthesized via amidation of sodium alginate with deferoxamine mesylate as determined by H‐NMR and elemental analysis. SA‐DFA with different graft yield was obtained by adjusting the ratio of sodium alginate and deferoxamine mesylate. It was found that aqueous solution of SA‐DFA could form hydrogel spontaneously due to hydrogen bonding interactions, which also endowed the SA‐DFA hydrogel with self‐healing capability. The healing efficiency of SA‐DFA hydrogels ranged from 53.64 to 90.16%. In addition, surface morphologies of SA‐DFA hydrogels before/after self‐healing process were demonstrated by SEM images. We anticipated that such self‐healable alginate hydrogel would be applied in the field of wound healing. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 856–865     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

Injectable and self-healing hydrogels with tissue adhesiveness and antibacterial activity as wound dressings for infected wound healing

The design of wound dressings with excellent self-healing ability, adequate adhesion, good biocompatibility, and potential antibacterial ability is of great significance for the healing of infected wounds arising from human activities. Herein, a series of multi-functional hydrogel dressings, poly(ionized isocyanoethyl methacrylate-glutamine)/poly(hexamethylene guanidine) (iG_x/PHMG_y) hydrogels, were obtained through homopolymerization of fully ionized isocyanoethyl methacrylate-glutamine (iIEM-Gln) in the presence of poly(hexamethylene guanidine) (PHMG), in which strong hydrogen bonds were formed among urea groups in the P (iIEM-Gln) chain to form a stable hydrogel network. The prepared iG_x/PHMG_y hydrogels exhibited adequate self-healing ability and tissue adhesion, which could be firmly adhered to the wound surface and remained intact during application. In addition, the presence of PHMG imparted good antibacterial activity to the hydrogels for the effective promotion of the wound healing in S. aureus infected skin wound on mice. Overall, this multi-functional hydrogel provides a facile and effective strategy for the design of infected wound dressings, and may show great potential in clinical applications.     

Cross‐linking induced thermoresponsive hydrogel with light emitting and self‐healing property

Development of self‐healing hydrogels with thermoresponse is very important for artificial smart materials. In this article, the self‐healing hydrogels with reversible thermoresponses were designed through across‐linking‐induced thermoresponse (CIT) mechanism. The hydrogels were prepared from ketone group containing copolymer bearing tetraphenyl ethylene (TPE) and cross‐linked by naphthalene containing acylhydrazide cross‐linker. The mechanical property, light emission, self‐healing, and thermo‐response of the hydrogels were investigated intensively. With regulation of the copolymer composition, the hydrogels showed thermoresponse with the LCST varied from above to below body temperature. At the same time, the hydrogels showed self‐healing property based on the reversible characteristic of the acylhydrazone bond. The hydrogel also showed temperature‐regulated light emission behavior based on AIE property of the TPE unit. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 869–877     

On‐Demand Dissolution of a Dendritic Hydrogel‐based Dressing for Second‐Degree Burn Wounds through Thiol–Thioester Exchange Reaction

An adhesive yet easily removable burn wound dressing represents a breakthrough in second‐degree burn wound care. Current second‐degree burn wound dressings absorb wound exudate, reduce bacterial infections, and maintain a moist environment for healing, but are surgically or mechanically debrided from the wound, causing additional trauma to the newly formed tissues. We have developed an on‐demand dissolvable dendritic thioester hydrogel burn dressing for second‐degree burn care. The hydrogel is composed of a lysine‐based dendron and a PEG‐based crosslinker, which are synthesized in high yields. The hydrogel burn dressing covers the wound and acts as a barrier to bacterial infection in an in vivo second‐degree burn wound model. A unique feature of the hydrogel is its capability to be dissolved on‐demand, via a thiol–thioester exchange reaction, allowing for a facile burn dressing removal.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

An Amino‐Acid‐Based Self‐Healing Hydrogel: Modulation of the Self‐Healing Properties by Incorporating Carbon‐Based Nanomaterials

An amino‐acid‐based (11‐(4‐(pyrene‐1‐yl)butanamido)undecanoic acid) self‐repairing hydrogel is reported. The native hydrogel, as well as hybrid hydrogels, have been thoroughly characterized by using various microscopic techniques, including transmission electron microscopy (TEM), atomic force microscopy (AFM), Raman spectroscopy, fluorescence spectroscopy, FTIR spectroscopy, X‐ray diffraction, and by using rheological experiments. The native hydrogel exhibited interesting fluorescence properties, as well as a self‐healing property. Interestingly, the self‐healing, thixotropy, and stiffness of the native hydrogel can be successfully modulated by incorporating carbon‐based nanomaterials, including graphene, pristine single‐walled carbon nanotubes (Pr‐SWCNTs), and both graphene and Pr‐SWCNTs, within the native gel system. The self‐recovery time of the gel was shortened by the inclusion of reduced graphene oxide (RGO), Pr‐SWCNTs, or both RGO and Pr‐SWCNTs. Moreover, hybrid gels that contained RGO and/or Pr‐SWCNTs exhibited interesting semiconducting behavior.     

An Injectable Self‐Healing Hydrogel Based on Chain‐Extended PEO‐PPO‐PEO Multiblock Copolymer

Injectable hydrogels have been commonly used as drug‐delivery vehicles and tried in tissue engineering. Injectable self‐healing hydrogels have great advantage over traditional injectable hydrogels because they can be injected as a liquid and then rapidly form bulk gels in situ at the target site under physiological conditions. This study develops an injectable thermosensitive self‐healing hydrogel based on chain‐extended F127 (PEO₉₀‐PPO₆₅‐PEO₉₀) multi‐block copolymer (m‐F127). The rapid sol–gel transition ability under body temperature allows it to be used as injectable hydrogel and the self‐healing property allows it to withstand repeated deformation and quickly recover its mechanical properties and structure through the dynamic covalent bonds. It is hoped that the novel strategy and the fascinating properties of the hydrogel as presented here will provide new opportunities with regard to the design and practical application of injectable self‐healing hydrogels.

     

Recent advances on herb‐derived constituents‐incorporated wound‐dressing materials: A review

Since ancient times, wound dressings have evolved with persistent and substantial changes. Several efforts have been made toward the development of new dressing materials, which can meet the demanding conditions for the treatment of skin wounds. Currently, many studies have been focused on the production and designing of herb‐incorporated wound dressings. Herb‐derived constituents are more effective than conventional medicines because of their nontoxic nature and can be administered over long periods. Herbal medicines in wound healing provide a suitable environment for aiding the natural course of healing. This review mainly focuses on the diverse approaches that have been developed to produce a wound dressing material, which can deliver herb‐derived bioactive constituents in a controlled manner. This review also discusses the common wound‐dressing materials available, basic principles of wound healing, and wound‐healing agents from medicinal plants.     

A Shear-Thinning,Self-Healing,Dual-Cross Linked Hydrogel Based on Gelatin/Vanillin/Fe3+/AGP-AgNPs: Synthesis,Antibacterial, and Wound-Healing Assessment

A shear-thinning and self-healing hydrogel based on a gelatin biopolymer is synthesized using vanillin and Fe³⁺ as dual crosslinking agents. Rheological studies indicate the formation of a strong gel found to be injectable and exhibit rapid self-healing (within 10 min). The hydrogels also exhibited a high degree of swelling, suggesting potential as wound dressings since the absorption of large amounts of wound exudate, and optimum moisture levels, lead to accelerated wound healing. Andrographolide, an anti-inflammatory natural product is used to fabricate silver nanoparticles, which are characterized and composited with the fabricated hydrogels to imbue them with anti-microbial activity. The nanoparticle/hydrogel composites exhibit activity against Escherichia coli, Staphylococcus aureus, and Burkholderia pseudomallei, the pathogen that causes melioidosis, a serious but neglected disease affecting southeast Asia and northern Australia. Finally, the nanoparticle/hydrogel composites are shown to enhance wound closure in animal models compared to the hydrogel alone, confirming that these hydrogel composites hold great potential in the biomedical field.     

An Extracellular Matrix‐Mimicking Hydrogel for Full Thickness Wound Healing in Diabetic Mice

An extracellular matrix‐mimicking hydrogel is developed consisting of a hyaluronan‐derived component with anti‐inflammatory activity, and a gelatin‐derived component offering adhesion sites for cell anchorage. The in situ‐forming hyaluronan‐gelatin (HA‐GEL) hydrogel displays a sponge‐like microporous morphology. Also, HA‐GEL shows a rapid swelling pattern reaching maximum weight swelling ratio within 10 min, while at the equilibrium state, fully swollen hydrogels display an exceedingly high water content with ≈2000% of the dry gel weight. Under typical 2D cell culture conditions, murine 3T3 fibroblasts adhere to, and proliferate on top of the HA‐GEL substrates, which demonstrate that HA‐GEL provides a favorable microenvironment for cell survival, adhesion, and proliferation. In vivo healing study further demonstrates HA‐GEL as a viable and effective treatment option to improve the healing outcome of full thickness wounds in diabetic mice by effectively depleting the inflammatory chemokine monocyte chemoattractant protein‐1 in the wound bed.     

Natural okra-based hydrogel for chronic diabetic wound healing

As a representative of chronic wounds, the long-term high levels of oxidative stress and blood sugar in chronic diabetic wounds lead to serious complications, making them the biggest challenge in the research on wound healing. Many edible natural biomaterials rich in terpenes, phenols, and flavonoids can act as efficient antioxidants. In this study, okra extract was selected as the main component of a wound dressing. The okra extracts obtained via different methods comprehensively maintained the bioactivity of multiple molecules. The robust antioxidant properties of okra significantly reduced intracellular reactive oxygen species production, thereby accelerating the wound healing process. The results showed that okra extracts and their hydrogel dressings increased cell migration, angiogenesis, and re-epithelization of the chronic wound area, considerably promoting wound remodeling in diabetic rats. Therefore, okra-based hydrogels are promising candidates for skin regeneration and wider tissue engineering applications.     

可注射水凝胶在伤口敷料中的研究进展

目前,在伤口治疗中对伤口敷料的选择越来越严格。传统的伤口敷料如纱布、绷带、海绵等在伤口愈合过程中容易诱发细菌感染,延缓伤口愈合,甚至引发慢性并发症。可注射水凝胶具备良好的生物相容性,能够适应伤口的形状以填充伤口,且具备一定的抗菌活性,从而避免伤口感染,相比传统的水凝胶伤口敷料更具备医疗优势,因此在生物医药领域得到广泛关注。本文对天然型可注射水凝胶和复合型可注射水凝胶在伤口愈合中的研究进展进行了综述;也对可注射水凝胶的未来发展趋势进行了展望。     

A Self‐Healing Integrated All‐in‐One Zinc‐Ion Battery

The self‐healing of zinc‐ion batteries (ZIBs) will not only significantly improve the durability and extend the lifetime of devices, but also decrease electronic waste and economic cost. A poly(vinyl alcohol)/zinc trifluoromethanesulfonate (PVA/Zn(CF₃SO₃)₂) hydrogel electrolyte was fabricated by a facile freeze/thaw strategy. PVA/Zn(CF₃SO₃)₂ hydrogels possess excellent ionic conductivity and stable electrochemical performance. Such hydrogel electrolytes can autonomously self‐heal by hydrogen bonding without any external stimulus. All‐in‐one integrated ZIBs can be assembled by incorporating the cathode, separator, and anode into hydrogel matrix since the fabrication of PVA/Zn(CF₃SO₃)₂ hydrogel is a process of converting the liquid to quasi‐solid state. The ZIBs show an outstanding self‐healing and can recover electrochemical performance completely even after several cutting/healing cycles.     

Poly(N‐isopropylacrylamide)‐based comb‐type grafted hydrogel with rapid response to blood glucose concentration change at physiological temperature

A new type of glucose‐responsive hydrogel with rapid response to blood glucose concentration change at physiological temperature has been successfully developed. The polymeric hydrogel contains phenylboronic acid (PBA) groups as glucose sensors and thermo‐responsive poly (N‐isopropylacrylamide) (PNIPAM) groups as actuators. The response rate of the hydrogel to environmental glucose concentration change was significantly enhanced by introducing grafted poly(N‐isopropylacrylamide‐co‐3‐acrylamidophenylboronic acid) [poly(NIPAM‐co‐AAPBA)] side chains onto crosslinked poly(NIPAM‐co‐AAPBA) networks for the first time. The synthesized comb‐type grafted poly(NIPAM‐co‐AAPBA) hydrogels showed satisfactory equilibrium glucose‐responsive properties, and exhibited much faster response rate to glucose concentration change than normal type crosslinked poly(NIPAM‐co‐AAPBA) hydrogels at physiological temperature. Such glucose‐responsive hydrogels with rapid response rate are highly attractive in the fields of developing glucose‐responsive sensors and self‐regulated drug delivery systems. Copyright © 2008 John Wiley & Sons, Ltd.     

Enzymetically Regulating the Self‐Healing of Protein Hydrogels with High Healing Efficiency

Enzyme‐mediated self‐healing of dynamic covalent bond‐driven protein hydrogels was realized by the synergy of two enzymes, glucose oxidase (GOX) and catalase (CAT). The reversible covalent attachment of glutaraldehyde to lysine residues of GOX, CAT, and bovine serum albumin (BSA) led to the formation and functionalization of the self‐healing protein hydrogel system. The enzyme‐mediated protein hydrogels exhibit excellent self‐healing properties with 100 % recovery. The self‐healing process was reversible and effective with an external glucose stimulus at room temperature.     

Developing a Self‐Healing Supramolecular Nucleoside Hydrogel Based on Guanosine and Isoguanosine

Recently, supramolecular hydrogels have attracted increasing interest owing to their tunable stability and inherent biocompatibility. However, only few studies have been reported in the literature on self‐healing supramolecular nucleoside hydrogels, compared to self‐healing polymer hydrogels. In this work, we successfully developed a self‐healing supramolecular nucleoside hydrogel obtained by simply mixing equimolar amounts of guanosine (G) and isoguanosine (isoG) in the presence of K⁺. The gelation properties have been studied systematically by comparing different alkali metal ions as well as mixtures with different ratios of G and isoG. To this end, rheological and phase diagram experiments demonstrated that the co‐gel not only possessed good self‐healing properties and short recovery time (only 20 seconds) but also could be formed at very low concentrations of K⁺. Furthermore, nuclear magnetic resonance (NMR), powder X‐ray diffraction (PXRD), and circular dichroism (CD) spectroscopy suggested that possible G₂isoG₂‐quartet structures occurred in this self‐healing supramolecular nucleoside hydrogel. This co‐gel, to some extent, addressed the problem of isoguanosine gels for the applications in vivo, which showed the potential to be a new type of drug delivery system for biomedical applications in the future.     

Effect of gamma‐irradiation sterilization on the physical and mechanical properties of a hybrid wound dressing

A wound dressing should ideally provide an optimal healing environment which enables rapid healing. It should maintain a moist environment at the wound surface, allow gas exchange, act as a barrier to microorganisms, remove excess exudates and afford mechanical protection to the wound. A new bioresorbable hybrid wound dressing which combines a poly(DL‐lactic‐co‐glycolic acid) porous top layer with a spongy collagen sublayer was developed and studied. The top layer contained the antibiotic drug gentamicin for controlled release to the wound site. It is of very high importance to use an appropriate sterilization process for this special new wound dressing, which will not have a deleterious effect on its function. Our investigation therefore focused on the effects of gamma‐irradiation sterilization (10, 25, 35 and 50 kGy) on the structure properties of this wound dressing. The physical and mechanical properties were of the wound dressings were affected by the gamma irradiation because of a combination of chain scission and crosslinking of the collagen layer mainly. The weight loss and water vapor transmission rate were increased, while the water uptake was decreased with the increase in the irradiation dose. The changes were small when doses of 10 or 25 kGy were applied at room temperature. The gamma‐irradiation resulted in stronger but more brittle wound dressings. These trends were smaller when the sterilization process was carried out in liquid nitrogen. Our research shows that gamma‐sterilization process is feasible for our new concept of hybrid wound dressings and optimal conditions can be chosen. Copyright © 2016 John Wiley & Sons, Ltd.     

Reinforcement of Self‐Healing Polyacrylic Acid Hydrogel with Acrylamide Modified Microcrystalline Cellulose†

Self‐healing hydrogel such as polyacrylic acid (PAA) hydrogel has attracted increasing attention based on its promising potential applications. However, it usually suffers from low strength especially as mechanical device. Herein, a commercial microcrystalline cellulose (MCC) was modified with acrylamide to graft polyacrylamide (PAM) chains on the particle surface. The acrylamide‐modified MCC (AM‐MCC) was then dispersed in monomer solution of acrylic acid to prepare composite hydrogel. The mechanical properties of the obtained composite hydrogels and the self‐healed hydrogels were carefully measured by compressive and tensile tests, and by dynamic mechanical analysis. Our results demonstrate that introduction of a small amount of AM‐MCC such as 3 wt% can not only reinforce the original hydrogel and the healed hydrogel markedly, but also improve self‐healing efficiency obviously. The analyses indicate that in addition to the reversible multi‐interactions such as hydrogen bonding and ionic interactions, the entanglements between the PAA chains of the hydrogel matrix and the PAM chains grafted on the MCC particles have also played an important role on the improvement in mechanical performances and the healing ability of the hydrogel. Moreover, the responsiveness to exterior ion has been tested to indicate potential application of the composite hydrogel as self‐healable sensor.