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.     

Acetate chitosan with CaCO3 doping form tough hydrogel for hemostasis and wound healing

In recent years, chitosan has been applied for wound management due to its properties of biocompatibility, biodegradability, antimicrobial activity, and low immunogenicity. But the poor water solubility in neutral pH limited its further application in clinical wound healing. To overcome this problem, acetate chitosan was developed and approved as commercial products for wound healing. However, the acidity of acetate chitosan was potentially allergenic, and the poor mechanical properties of its formed hydrogels also hindered the therapeutic efficacy in wound care. In this study, CaCO₃ was simply doped into acetate chitosan to form the wound dressing. After absorbing water, the H⁺ of acetate chitosan reacted with CaCO₃ to release Ca²⁺, resulting in acidity decreased. The production of Ca²⁺ and residue of CaCO₃ cross‐linked with chitosan to form a tough hydrogel by electrostatic interaction. The physical characteristics, swelling, mechanical testing, and blood clotting were evaluated. The results in vitro demonstrated that after doping CaCO₃ into acetate chitosan, the mechanical properties and blood clotting of the formed hydrogel were increased. Then, the evaluation of hydrogels in vivo revealed that it can also accelerate the wound healing by promoting re‐epithelization and collagen deposition. This simple way by doping CaCO₃ into acetate chitosan can increase wound healing, and it can also broad the application of acetate chitosan in clinical use.     

Preparation of Multi-Functional Quaternary Ammonium Chitosan/Surfactin Hydrogel and its Application in Wound Management

Hydrogel with a 3D network structure can cover the wound to stop the bleeding and support the host tissue infiltration and integration. In this study, an antibacterial hydrogel with hemostasis and the ability to promote wound healing is proposed. This hydrogel comprised surfactin, polyvinylpyrrolidone, and methacrylic anhydride (MA) grafted quaternary ammonium chitosan (CS-MA). The hydrogel formation is triggered by the ultraviolet-initiated polymerization of CS-MA, while the surfactin is complexed with the hydrogel through hydrogen bonding interaction. The results showed that this hydrogel is an adhesive hydrogel with shape adaptability, which can cover the wound surface and promote contact between the hydrogel and the wound surface. More importantly, this hydrogel can simulate the microenvironment of the primary extracellular matrix and increase collagen deposition, and inflammatory factor transformation. The designing of such a multi-functional hydrogel is expected to provide a novel approach to promoting the healing of wounds.     

A Spray‐Filming Self‐Healing Hydrogel Fabricated from Modified Sodium Alginate and Gelatin as a Bacterial Barrier

Self‐healing hydrogels as wound dressings still face challenges in infection prevention, especially in the dressing of mass wounds, due to their inflexibility and the slow formation of the protective film on the wound. Therefore, designing a spray‐filming (rapid‐forming) hydrogel that can serve as a bacterial barrier is of particular significance in the development of wound dressings. Here, a self‐healing hydrogel based on adipic acid dihydrazide‐modified gelatin (Gel‐ADH) and monoaldehyde‐modified sodium alginate(SA‐mCHO) is prepared. Using dynamic, Schiff base bonds, the hydrogels exhibit excellent self‐healing properties. Moreover, the gelation time of SA‐mCHO/Gel‐ADH (SG) hydrogels is shortened to 2–21 s, resulting in rapid filming by spraying the two precursor solutions. In addition, the rapid spray‐filming ability might offer sufficient flexibility and rapidity for dealing with mass and irregular wounds. Notably, the bacterial barrier experiments show that the SG hydrogel films could form an effective barrier to Staphylococcus aureus and Candida albicans for 12 h. Therefore, SG hydrogels could be used in wound dressings and they show great promise in applications associated with mass and irregular traumas.     

The Effect of Rainbow Trout (Oncorhynchus mykiss) Collagen Incorporated with Exo-Polysaccharides Derived from Rhodotorula mucilaginosa sp. on Burn Healing

Burn is one of the physically debilitating injuries that can be potentially fatal; therefore, providing appropriate coverage in order to reduce possible mortality risk and accelerate wound healing is mandatory. In this study, collagen/exo-polysaccharide (Col/EPS 1–3%) scaffolds are synthesized from rainbow trout (Oncorhynchus mykiss) skins incorporated with Rhodotorula mucilaginosa sp. GUMS16, respectively, for promoting Grade 3 burn wound healing. Physicochemical characterizations and, consequently, biological properties of the Col/EPS scaffolds are tested. The results show that the presence of EPS does not affect the minimum porosity dimensions, while raising the EPS amount significantly reduces the maximum porosity dimensions. Thermogravimetric analysis (TGA), FTIR, and tensile property results confirm the successful incorporation of the EPS into Col scaffolds. Furthermore,the biological results show that the increasing EPS does not affect Col biodegradability and cell viability, and the use of Col/EPS 1% on rat models displays a faster healing rate. Finally, histopathological examination reveals that the Col/EPS 1% treatment accelerates wound healing, through greater re-epithelialization and dermal remodeling, more abundant fibroblast cells and Col accumulation. These findings suggest that Col/EPS 1% promotes dermal wound healing via antioxidant and anti-inflammatory activities, which can be a potential medical process in the treatment of burn wounds.     

Bioactive peptides grafted silicone dressings: A simple and specific method

The need for bioactive dressings increases with the population aging and the prevalence of chronic diseases. In contrast, there are very few dressings on the market which are designed to display a chosen bioactivity. In this context, we investigated the surface-functionalization of silicone wound dressing with bioactive peptides. One of the challenges was to avoid multistep grafting reactions involving catalysts, solvents or toxic reagents, which are not suitable for the fabrication of medical devices at an industrial scale. In the other hand, a covalent bonding was necessary to avoid the loss of the biological effect by progressive removal of the peptide in biological fluids generated by the wound. To solve these limitations, we developed a strategy allowing an easy and direct functionalization of silicone. This strategy relies on hybrid silylated bioactive peptides, which chemoselectively react with plasma-activated silicone surfaces. We synthesized three hybrid peptides with wound healing properties, which were grafted on commercially available silicone dressings Cerederm^® and Mepitel^®. Grafted dressings were evaluated in vitro and enabled a quicker scare recovery and extracellular matrix deposition with human dermal fibroblasts. These results were confirmed by in vivo studies showing an enhanced wound-healing of the pig skin. By this simple method, we transformed inert dressing into bioactive dressing which showed properties of wound healing.     

POSS-modified PEG adhesives for wound closure

PEG-related adhesives are limited in clinical use because they are easy to swell and cannot support the cell growth.In this study,we produced a series of POSS-modified PEG adhesives with high adhesive strength.Introduction of inorganic hydrophobic POSS units decreased the swelling of the adhesives and enhanced cell adhesion and growth.The in vitro cytotoxicity and in vivo inflammatory response experiments clearly demonstrated that the adhesives were nontoxic and possessed excellent biocompatibility.Compared with the sutured wounds,the adhesive-treated wounds showed an accelerated healing process in wounded skin model of the Bama miniature pig,demonstrating that the POSS-modified PEG adhesive is a promising candidate for wound closure.     

Biomimetic hybrid scaffold containing niosomal deferoxamine promotes angiogenesis in full-thickness wounds

Effective management of full-thickness wounds faces significant challenges due to poor angiogenesis and impaired healing. Biomimetic tissue-engineered scaffolds with angiogenic properties can, however, enhance the regeneration capacity of the damaged skin. Here, we developed a hybrid double-layer nanofibrous scaffold, comprised of egg white (EW) and polyvinyl alcohol (PVA), loaded with niosomal Deferoxamine (NDFO) for enhanced angiogenesis and wound healing features. The hybrid scaffold showed enhanced mechanical properties with comparable modulus and shape-recovery behavior of the human skin. Thanks to the porous morphology and uniform distribution of NDFO within the nanofibers, in vitro drug release studies indicated controlled and sustained release of DFO for up to 9 days. The constructs also promoted a significant increase in vascular sprouting area in vitro and enhanced vascular branches ex vivo. In vivo, implantation of the hybrid scaffold in full-thickness wounds in rats revealed early angiogenic response, a higher number of neo-formed vessels, a faster healing rate and complete epithelialization as early as day 10, compared to the control groups. Thus, the presented biomimetic hybrid scaffold with DFO control release features holds great promise in accelerated full-thickness wound healing and soft tissue regeneration.     

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.     

A reinforced nanofibrous patch with biomimetic mechanical properties and chondroinductive effect for rotator cuff tissue engineering

Patch augmented surgery has been a feasible technique for rotator cuff repair. An ideal rotator cuff tissue engineering patch should have proper mechanical properties to match the native tendons and sufficient biological effect to promote tendon-bone healing. In this study, kartogenin (KGN)-grafted poly (ether-ester-urethane)urea/gelatin composite nanofibrous patches (PEEUU-GEL-KGN) were fabricated via electrospinning process followed by crosslinking of GEL and covalent grafting of KGN. The optimized PEEUU-GEL-KGN nanofibrous patches exhibited biomimetic mechanical properties, including sufficient tensile strength, non-linear stress-strain profiles, and remarkable elasticity and cyclical properties. In vitro investigations revealed that the patches possessed outstanding biocompatibility and performed a sustained release of KGN for a long time. Modification with GEL and KGN significantly improved hydrophilicity of the patches, promoted the adhesion, spreading, and proliferation of mesenchymal stem cells and upregulated the expression of cartilage-related genes. In vivo studies demonstrated that the implanted PEEUU-GEL-KGN patches effectively improved the tissue cellularity and collagen alignment, accelerated the fibrocartilage regeneration, augmented the biomechanical strength of the repaired enthesis, and reinforced the fixing of the tendon to the bone. Overall, the PEEUU-GEL-KGN patches enhanced tendon-bone healing and resisted rotator cuff re-tear. Therefore, the PEEUU-GEL-KGN patch is a highly promising candidate for rotator cuff tissue engineering.     

Collagen Peptides Derived from Sipunculus nudus Accelerate Wound Healing

Marine collagen peptides have high potential in promoting skin wound healing. This study aimed to investigate wound healing activity of collagen peptides derived from Sipunculus nudus (SNCP). The effects of SNCP on promoting healing were studied through a whole cortex wound model in mice. Results showed that SNCP consisted of peptides with a molecular weight less than 5 kDa accounted for 81.95%, rich in Gly and Arg. SNCP possessed outstanding capacity to induce human umbilical vein endothelial cells (HUVEC), human immortalized keratinocytes (HaCaT) and human skin fibroblasts (HSF) cells proliferation and migration in vitro. In vivo, SNCP could markedly improve the healing rate and shorten the scab removal time, possessing a scar-free healing effect. Compared with the negative control group, the expression level of tumor necrosis factor-α, interleukin-1β and transforming growth factor-β1 (TGF-β1) in the SNCP group was significantly down-regulated at 7 days post-wounding (p < 0.01). Moreover, the mRNA level of mothers against decapentaplegic homolog 7 (Smad7) in SNCP group was up-regulated (p < 0.01); in contrast, type II TGF-β receptors, collagen I and α-smooth muscle actin were significantly down-regulated at 28 days (p < 0.01). These results indicate that SNCP possessed excellent activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to reducing inflammation, improving collagen deposition and recombination and blockade of the TGF-β/Smads signal pathway. Therefore, SNCP may have promising clinical applications in skin wound repair and scar inhibition.     

Novel Poly(vinyl alcohol)/Chitosan/Modified Graphene Oxide Biocomposite for Wound Dressing Application

Rapid absorption of wound exudate and prevention of wound infection are prerequisites for wound dressing to accelerate wound healing. In this study, a novel kind of promising wound dressing is developed by incorporating polyhexamethylene guanidine (PHMG)‐modified graphene oxide (mGO) into the poly(vinyl alcohol)/chitosan (PVA/CS) matrix, conferring the dressing the required mechanical properties, higher water vapor transmission rate (WVTR), less swelling time, improved antibacterial activity, and more cell proliferation compared to the PVA/CS film crosslinked by genipin. In vivo experiments indicate that the PVA/CS/mGO composite film can accelerate wound healing via enhancement of the re‐epithelialization. PVA/CS/mGO composite film with 0.5 wt% mGO sheets displays the best wound healing properties, as manifested by the 50% higher antibacterial rate compared to GO and the wound healing rate of the mouse using this dressing is about 41% faster than the control group and 31% faster than the pure PVA/CS dressing. The underlying mechanism of the accelerated wound healing properties may be a result of the improved antibacterial ability to eradicate pathogenic bacteria on the wound area and maintain an appropriate moist aseptic wound healing environment to accelerate re‐epithelialization. These findings suggest that this novel composite PVA/CS/mGO film may have promising applications in wound dressing.     

Effect of laser dose and treatment schedule on excision wound healing in diabetic mice

The present study was undertaken to evaluate a He-Ne laser (632.8 nm; 7 mW; 4.02 mW cm(-2); 15 mm spot size) dose and the treatment schedule on diabetic wound healing in a mouse model. Circular wounds of 15 mm diameter were created on streptozotocin induced diabetic Swiss albino mice, and were uniformly illuminated with the single exposure of various He-Ne laser doses of 1, 2, 3, 4 and 5 J cm(-2) respectively. Further, the treatment schedule was also optimized by exposing the wounds with 3 J cm(-2) at 0, 24 h, 48 h postwounding. Contraction kinetics, mean area under the curve and the mean healing time of the wounds were computed along with the collagen and the glucosamine levels in the wound ground tissues at various postwounding treatment schedules. Results of this study indicated that the single exposure of 3 J cm(-2) laser dose applied immediately after the wounding caused a significant reduction in the mean area under the curve and the mean healing time along with the elevated levels of collagen and glucosamine contents in the tissue compared to the controls. In conclusion, He-Ne laser dose of 3 J cm(-2) applied immediately after the wounding has demonstrated optimum wound healing compared to the other doses and treatment schedules.     

Bioaerogels: Promising Nanostructured Materials in Fluid Management,Healing and Regeneration of Wounds

Wounds affect one’s quality of life and should be managed on a patient-specific approach, based on the particular healing phase and wound condition. During wound healing, exudate is produced as a natural response towards healing. However, excessive production can be detrimental, representing a challenge for wound management. The design and development of new healing devices and therapeutics with improved performance is a constant demand from the healthcare services. Aerogels can combine high porosity and low density with the adequate fluid interaction and drug loading capacity, to establish hemostasis and promote the healing and regeneration of exudative and chronic wounds. Bio-based aerogels, i.e., those produced from natural polymers, are particularly attractive since they encompass their intrinsic chemical properties and the physical features of their nanostructure. In this work, the emerging research on aerogels for wound treatment is reviewed for the first time. The current scenario and the opportunities provided by aerogels in the form of films, membranes and particles are identified to face current unmet demands in fluid managing and wound healing and regeneration.     

In vitro wound healing evaluation,antioxidant and chemical profiling of Baeckea frutescens leaves ethanolic extract

Occurrence of the wound or chronic wound, which results to disability, amputation and diminish quality of life, are leading to increased healthcare expenditure around the globe. Despite effective conventional wound healing medicines, the exploration of alternative medicines are continuing process as researchers seek for the approach to reduce the cost of wound healing management. In present study, wound healing properties of ethanolic extract of Baeckea frutescens leaves were determined by evaluating their cytotoxicity, proliferation and migration rate on two types of cells, keratinocytes (HaCaT) and fibroblasts (BJ). Furthermore, the antioxidant properties of this plant were determined by DPPH scavenging, ferric reducing antioxidant power (FRAP) and total phenolics content (TPC) assays. The phytochemistry of the extract was evaluated by phytochemicals screening and liquid chromatography mass spectrometry (LCMS) analysis. Results of this study indicated Baeckea frutescens extract increased the rate of proliferation and migration on both HaCat and BJ cells within their nontoxic doses. The extract also possessed a very good antioxidant property as demonstrated with high DPPH radical scavenging, FRAP and TPC values, comparable to that of Green tea extract, a widely known antioxidant. The phytochemistry analyses and LCMS exhibited the presence saponins, flavonoids, tannins and steroids in Baeckea frutescens extract possibly responsible to their antioxidant and wound healing properties.     

Chitosan and radiation chemistry

Chitosan as a raw material with special properties has drawn attention of scientists working in the field of radiation processing and natural polymer products development, and also of specialists working in the field of radiation protection and oncologists. Especially the applications concern reduced molecular weight chitosan which still retain its chemical structure; such form of the compound is fostering biological, physical and chemical reactivity of the product. Chitosan degrades into fragments under γ-ray or electron beam irradiation. Antibacterial properties of the product are applied in manufacturing hydrogel for wound dressing and additional healing properties can be achieved by incorporating in the hydrogel matrix chitosan bonded silver clusters. Another possible application of chitosan is in reducing radiation damage to the radiation workers or radiation cured patients. In the case of radioisotopes oral or respiratory chitosan-based materials can be applied as chelators. Applications of chitosan in oncology are also reported.     

Hyaluronic acid-methacrylic anhydride/polyhexamethylene biguanide hybrid hydrogel with antibacterial and proangiogenic functions for diabetic wound repair

Diabetic wounds lead to a decrease in quality of life and an increase in mortality. Current treatment strategies include preventing bacterial adhesion while improving microcirculation. As a new type of wound dressing that imitates natural skin, hydrogel has gradually emerged with its excellent properties. However, existing hydrogels rarely achieve satisfactory results in promoting wound repair and antibacterial simultaneously. In this case, we prepared methacrylic anhydride chemically modified hyaluronic acid as a hydrogel matrix, added polyhexamethylene biguanide as an antibacterial component, and loaded sodium alginate/salidroside composite microspheres which could sustainably release salidroside and thus promote angiogenesis. Hybrid hydrogel (HAMA/PHMB-Ms) was synthesized via photocrosslinking, and its chemical structure, particle size distribution and microstructure were characterized. The satisfactory antibacterial properties of the HAMA/PHMB(15%)-Ms hydrogel were studied in vitro, and its antibacterial rates against E. coli and S. aureus were 97.85% and 98.56%, respectively. In addition, after demonstrating its good biocompatibility, we verified that the HAMA/PHMB-Ms hydrogel has increased granulation tissue formation, more collagen deposition, more subcutaneous capillary formation, and better wound healing than blank control, HAMA and HAMA/PHMB hydrogel on the back wound model of diabetic mice. The results confirmed that HAMA/PHMB-Ms hydrogel was a promising material for the treatment of the diabetic wounds.     

Real-time monitoring flexible hydrogels based on dual physically cross-linked network for promoting wound healing

To achieve smart and personalized medicine, the development of hydrogel dressings with sensing properties and biotherapeutic properties that can act as a sensor to monitor of human health in real-time while speeding up wound healing face great challenge. In the present study, a biocompatible dual-network composite hydrogel (DNCGel) sensor was obtained via a simple process. The dual network hydrogel is constructed by the interpenetration of a flexible network formed of poly(vinyl alcohol) (PVA) physical cross-linked by repeated freeze-thawing and a rigid network of iron-chelated xanthan gum (XG) impregnated with Fe³⁺ interpenetration. The pure PVA/XG hydrogels were chelated with ferric ions by immersion to improve the gel strength (compressive modulus and tensile modulus can reach up to 0.62 MPa and 0.079 MPa, respectively), conductivity (conductivity values ranging from 9 × 10⁻⁴ S/cm to 1 × 10⁻³ S/cm) and bacterial inhibition properties (up to 98.56%). Subsequently, the effects of the ratio of PVA and XG and the immersion time of Fe³⁺ on the hydrogels were investigated, and DNGel3 was given the most priority on a comprehensive consideration. It was demonstrated that the DNCGel exhibit good biocompatibility in vitro, effectively facilitate wound healing in vivo (up to 97.8% healing rate) under electrical stimulation, and monitors human movement in real time. This work provides a novel avenue to explore multifunctional intelligent hydrogels that hold great promise in biomedical fields such as smart wound dressings and flexible wearable sensors.     

Development of honey hydrogel dressing for enhanced wound healing

Radiation at 25 and 50 kGy showed no effect on the acidic pH of the local honey, Gelam, and its antimicrobial property against Staphylococcus aureus but significantly reduced the viscosity. Honey stored up to 2 years at room temperature retained all the properties studied. Radiation sterilized Gelam honey significantly stimulated the rate of burn wound healing in Sprague-Dawley rats as demonstrated by the increased rate of wound contraction and gross appearance. Gelam honey attenuates wound inflammation; and re-epithelialization was well advanced compared to the treatment using silver sulphadiazine (SSD) cream. To enhance further the use of honey in wound treatment and for easy handling, Gelam honey was incorporated into our hydrogel dressing formulation, which was then cross-linked and sterilized using electron beam at 25 kGy. Hydrogel with 6% of honey was selected based on the physical appearance.     

Anacyclus pyrethrum (L): Chemical Composition,Analgesic, Anti-Inflammatory,and Wound Healing Properties

Background: Anacyclus pyrethrum (A. pyrethrum) is a wild species belonging to the family Asteraceae, which is used in traditional medicines. Aim of the study: This work was undertaken to study the chemical composition, analgesic, anti-inflammatory, and wound healing properties of hydroalcoholic extracts of different parts (roots, seeds, leaves, and capitula) of A. pyrethrum. Material and Methods: The phytochemical analysis of the studied extracts was conducted by GC-MS. The analgesic activity was evaluated in mice using acetic acid and formaldehyde methods. The anti-inflammatory activity was tested using the inhibitory method of edema induced in rats. The healing activity of the hydroethanolic extracts was explored by excision and incision wound healing models in rats. Results: The phytochemical analysis of the studied plant extracts affirmed the presence of interesting compounds, including some newly detected elements, such as sarcosine, N-(trifluoroacetyl)-butyl ester, levulinic acid, malonic acid, palmitic acid, morphinan-6-One, 4,5.alpha.-epoxy-3-hydroxy-17-methyl, 2,4-undecadiene-8,10-diyne-N-tyramide, and isovaleric acid. The extracts of different parts (roots, seeds, leaves, and capitula) exhibited promising anti-inflammatory, analgesic, and wound healing effects, with percentages of inhibition up to 98%, 94%, and 100%, respectively. Conclusion: This study might contribute towards the well-being of society as it provides evidence on the potential analgesic, anti-inflammatory, and wound healing properties of A. pyrethrum.