Current Trends in Advanced Alginate-Based Wound Dressings for Chronic Wounds
Abstract
:1. Introduction
2. Chronic Wounds Mechanisms and Alginates Roles
3. Alginate Physical Properties
4. Alginate-Based Hydrogels for Wound Healing
5. Alginate-Based Beads and Microcapsules for Wound Healing
6. Alginate-Based Nanofibers and Fibers for Wound Healing
Composition | Study Type/Target | Ref. |
---|---|---|
2% Na ALG solution—16% PVA solution—0.5, 1, 2, 5% ZnO-NPs; Na ALG/PVA ratio 1:1 | Composite nanofiber characterization, antibacterial effect, cell adhesion potential, cytotoxicity | [11,87] |
Na ALG from unmodified methacrylated ALG—1% w/v RGD-modified methacrylated ALG—methacrylated heparin—4% w/v PEO; Na ALG/PEO ratio 1:1 | Nanofiber characterization, cell interaction, adhesion and proliferation, binding and releasing heparin tests | [28,96] |
4 wt % Na ALG—5 wt % PEO—0.5 wt % Triton X-100—5 wt % DMSO; Na ALG/PEO ratios: 65:35, 50:50, 35:65 | Nanofiber characterization, fibroblast proliferation | [86,94] |
8 wt % PVA—2% w/w Na ALG—3.2% w/v ciprofloxacin; PVA/Na ALG ratio: 5.5:1 | Nanofiber characterization, swelling, drug incorporation and release; in vivo tests on rabbits: drug release, wound healing | [94,95] |
1, 2, 3% wt of Na ALG—PEO—0.3 wt % Lecithin—5% w/w CaCl2; 1, 2, 3% wt of Na ALG/PEO weight % ratios: 1:1, 2:1, 3:1, 1:2, 2:2, 3:2 | Solution characterization: viscosity, conductivity; Nanofiber characterization: structure, water absorption, fibroblast attachment | [93,94] |
6% w/v Na ALG—0.1, 0.15, 2% chitin whisker Chitin whisker/ALG weight ratio: 0.05–2% | Whiskers and fibers characterization | [62,65,97] |
ZnCl2—Ca ALG fibers | Antimicrobial and immuno-modulatory effects for wound healing keratinocyte migration, ppm Zn release | [11,42,89,98,99] |
AgNO3—6% Ca ALG fibers | Antimicrobial effect | [11,89,98,100] |
0.5–0.75% w/v Chitosan—0.5–1% w/v ALG—Dexamethasone/BSA/PDGF-bb/Avidin fibers | Drug incorporation and release, PDGF-bb bioactivity | [49,90] |
0, 0.014, 0.041% w/v Chitosan—0.001% w/v Na ALG—Ninhydrin—CaCl2 in fibers | Filament characterization | [49,101] |
1.5 w % Na ALG—Ag-NPs in crosslinked fibers | Wound healing effect on SKH-1 mice | [102] |
7. Other Alginate-Based Dressings
Composition | Study Type/Target | Ref. |
---|---|---|
Na ALG—0.1% w/v I-labeled SDF-1 plasmid Na ALG—0.0001% w/v (1 ng/µL) I-labeled SDF-1 protein | Acute surgical wounds on Yorkshire pigs: SDF-1 release kinetics, wound healing rate, scar formation | [42,115] |
Viscose/silver/ALG Vis/Ag-NPs/ALG Viscose/silver/ALG/nicotinamide Viscose/silver/ALG/nicotinamide/CaCl2 0.5–1.5% w/w Na ALG in nonwoven fabric | Burn—diabetic rats | [105] |
Chitosan 4% w/v—1% w/w CH3COOH—4% ALG Chitosan 4% w/v—1% w/w CH3COOH—4% CG w/v—5.7% NaCl | Comparative drug release system study: swelling, Diltiazem HCl-loaded tablet formulation, dissolution in 1:1 complex systems | [116] |
Ca ALG versus silicone-coated polyamide net | Comparative randomized trial: healing and slippage rate, removal discomfort degree on skin graft donor sites | [117,118] |
2% w/v Na ALG—pH-responsive dye—glycerol 0–60% w/v | Flexible microfibers description, real-time pH modifications on the pig wound site | [112] |
collagen—0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0% alginic acid, at 3:1 ratio in cross-linked sheet | Sheet characterization | [98,119] |
75% Alginic acid solution 2% w/v– 45S5 bioactive glass—25% cell suspension | VEGF secretion, cell viability, cytotoxicity | [120] |
Polyox®—CG—Streptomycin—Diclofenac (0.75:0.25:0.3:0.25 g) Polyox®—0.5 g Na ALG—Streptomycin—Diclofenac (0.5:0.5:0.25:0.1 g) | Wafer characterization, adhesion, drug release, swelling | [23,111] |
2% w/v Alginic acid—murine antisense nucleotides (Cx43asODN) based scaffolds | Wounded ICR mice: inflammatory response, re-epithelization | [11,104] |
20 µg Smad3 ASOs in Na ALG and chitosan 1:1, 1:2, 1:4, 1:8, 1:16 ALG/chitosan ratio in PEC | Scaffold characterization, wound healing in C57BL/6 mice | [40,62,65] |
gelatin—1 wt % Na ALG (with or without 0.4 mg/cm2 AgSD) sponge | Wistar rat wound healing | [11,98,121] |
1% solution silk fibroin—1% solution alginic acid in 10:0, 5:5 and 0:10 ratios sponge | Sprague Dawley rats full thickness wound | [98,122] |
2 or 4% w/v high G and high M ALG—0.1–10% w/w PEG—9.5% w/v poly(D,L-lactide-co-glycolide) (PLGA)—0.5% w/v insulin microparticles in sponge | Sponge characterization: density, tensile strength, water vapor transmission rate and absorption capacity. In vitro study: interaction with HaCaT cells, insulin release | [23,114] |
Chitosan—1% w/w Na ALG—hematoxylin-eosin—DHEA—AgSD in PEC sponge | Microscope assay, in vitro drug release, cytotoxicity, antibacterial effect, in vivo burn healing on BALB/C mice | [49,123] |
ALG—0.2, 0.4% chitosan—0.1, 0.5% all-trans retinoic acid (ATRA). 1:10 ATRA/ALG ratio in microparticles | Microparticles characterization, encapsulation efficiency, dermal localization, ATRA skin release | [42,124] |
2% Na ALG (61% M and 39% G)—2–4 µg VEGF in microspheres | In vitro drug release, in vivo angiogenesis | [125] |
8. Commercially Available Pharmaceutical Alginate-Based Products
Name | Composition/Target | Study Type/Effects | Ref. |
---|---|---|---|
ALGS6 Ag (Prescribed/Over-The-Counter) | Ca ALG fiber—Lyocell fiber—1.7% Ag+ Surgical, traumatic, acute and chronic wounds, ulcers, first and second degree burns; Minor cuts, burns | Exudate absorption, gel forming, wound healing promoter if changed weekly | [142] |
Aquacel™ Ag EXTRA™ Hydrofiber™ (Prescribed/OTC) | Bi-layer Na ALG CMC—Ag+—strengthening fibers; Surgical, traumatic, exuding, infected, and painful wounds, second degree burns, ulcers or for minor cuts or burns | Bacterial inhibition, absorbs the wound exudate while forming a gel, it must be changed every 1–2 weeks | [142] |
Calgitrol™ foam or SilverSite™ | Ag+ in Ag ALG—Ca ALG—polyurethane foam | Antimicrobial effect, cytotoxicity | [23,143,144,145] |
Fibracol 10% Ca ALG in Fibracol Plus® dressing | 90% Collagen—10% Ca ALG; Exuding full- and partial-thickness wounds, second degree burns; diabetic, pressure, and venous ulcers | Clinical Trial: healing time of diabetic foot ulcers | [16,32,146] |
Flaminal® gel | ALG—PEG matrix—notatin—lactoperoxidase—guaiacol; burns, post-surgery wounds, diabetic, leg and pressure ulcers. If used with H2O2 and SCN- it has a bacteriostatic effect against both gram-positive and gram-negative bacteria. | Antimicrobial and bacteriostatic effect, wound surface moisturizer, exudate absorber, debrides necrotic tissue | [32,129,147,148] |
Guardix-SG® | Na ALG—poloxamer—CaCl2; post-surgery (silicone implantation, blepharoplasty) | In vivo post-surgery studies on rabbits: thermosensitive gel, mechanical barrier formation, suppression of capsular contracture, reduced inflammation and fibrosis | [32,149,150] |
Hyalogran® dressing | Hyaluronic acid ester—Na ALG; Leg and pressure sores, diabetic and ischemic wounds (with slough or necrosis) | Exudate absorption, gel transformation, necrotic tissue removal | [32,140] |
Kaltostat® | 80% High G Ca ALG—20% NaALG; Acute and chronic wounds with moderate to heavy exudate | Wound healing | [6,28,49,62,63,64,65,151] |
Luofucon® Antibacterial Alginate Wound Dressing (OTC) | Ca ALG—Ag; minor cuts, abrasions, and burns | Changed daily it has antibacterial effect and promotes wound healing | [126] |
Luofucon® Extra Silver Alginate Dressing (PO) | Ca ALG—Ag; moderate to heavily exuding wounds, ulcers, trauma-inflicted or post-operative wounds, infected wounds, grafts | Antibacterial effect for seven days and it promotes wound healing | [126] |
Medihoney® (gel, hydrogel or paste) | Ca ALG—Manuka honey; ulcers: hemorrhagic, heavily exuding, diabetic foot, leg (arterial or venous), pressure (partial or full-thickness) ulcers. First and second partial thickness burns. Surgical and traumatic wounds | Antibacterial effect | [3,23] |
Purilon Gel® | Na CMC—Ca ALG; Used with another dressing for first and second degree burns or sloughy and necrotic wounds | Wound surface moisturizer | [32,147,152,153] |
Saf-gel® | Carbomer propylene glycol sodium—Ca ALG; Abrasions, cuts, sloughy and necrotic wounds, second degree burns, non-infected diabetic foot ulcers, and pressure and venous ulcers | Wound healing and surface moisturizer. | [32,147,154] |
SeaSorb® fine foam sheet | Na ALG/Ca ALG—polyethylene net; Heavily exuding wounds: cavity wounds, second degree burns, diabetic, leg and pressure ulcers, spina bifida | Human clinical trials: fiber to gel transformation, tolerance, healing rate with reduced exudate, maceration and pain intensity | [32,155,156] |
Silvercel™ | 36% Ca ALG with high G—6% CMC—28% Ag (111 mg Ag/100 cm2)—30% EasyLift Precision Film (Acelity/Systagenix) | Pig and human trials, wound healing | [141,157,158,159,160,161,162] |
Tromboguard® bi-layer dressing | Polyurethane sponge—chitosan + Na ALG + Ca ALG + Ag+; Traumatic and post-surgery wounds | Antibacterial effect and strong hemostatic | [32] |
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Composition | Study Type/Target | Ref. |
---|---|---|
1% w/v Na ALG—0.1% w/v acacia gum—1 mg/mL ZnO-NPs | Characterization, healing effects and cytotoxicity on sheep fibroblasts, antibacterial activity | [29] |
0.5–2.5% w/v LF 200S ALG hydrogel emulsion + 0.9, 1.4, 2.8% Tween 80/Span 20/isopropyl myristate oil/Ketoprofen ratio 26:1.25:4:1 Ca2+/D (+) gluconic acid δ-lactone molar ratio: 1:2 Ketoprofen microemulsion: 0.9, 1.4, 2.8% | Characterization, drug release, scattering patterns | [56] |
alginate dialdehyde (ADA)—gelatin—0.1 M borax | Characterization and in vivo study on rat model | [57] |
60:20:2:4 w/w Na ALG—chitin/chitosan—fucoidan hydrogel sheet | Sprague-Dawley rats with full thickness wounds, gives a moist wound environment, easy application and removal, migration, cytotoxicity assay | [62,63,64,65,66] |
encapsulated TRAP—0.5% w/w chitosan—PV-Ca ALG hydrogel film | C57 black 6/CBA mice wound healing | [67] |
10 g ALG—4 mg trypan blue, 10 g ALG—10 µg VEGF | Drug release: in vitro and in vivo on NOD and SCID mice, angiogenesis | [68] |
1% heparin—1% Na ALG—bFGF | Characterization, angiogenesis and bFGF release profile in Wistar rats | [69] |
10 & 15% Polyvinyl pyrrolidone—0.5 and 1% ALG—0, 30, 50, 70, and 100 ppm Ag-NPs. | Characterization, crosslinking degree, antimicrobial activity. Best results: 0.5% ALG, 15% PVP, 70 ppm Ag-NPs | [48] |
Polyurethane foam—pH-sensitive Na ALG-bentonite hydrogels 1:0, 0.7:0.3, 0.5:0.5, 0.3:0.7 | Characterization, drug release from foam, cytotoxicity | [70] |
Micro-emulsion 20% Tea tree oil—1% w/v ALG hydrogel | Characterization, oil dispersion, antimicrobial effect | [71] |
10% Na ALG sulfate—CM11 peptide | Mouse wound healing | [72] |
ALG—k-CG ratio: 5:5, 7:3, 8:2 ALG—i-CG ratio: 5:5, 7:3, 8:2 | Formation and characterization; cytotoxicity, cell encapsulation | [73] |
VEGF—2 wt % Na ALG, VEGF—0.05% chitosan—2 wt % Na ALG VEGF—heparin-coated chitosan—2 wt % Na ALG | In vitro drug release | [74] |
2 wt % ALG—trypan blue, 2 wt % ALG—methylene blue, 2 wt % ALG—VEGF | In vitro drug release | [75,76] |
PEG diacrylate—thiolated ALG bilayered hydrogel with small extracellular vesicles (sEVs) | Characterization, rats and rabbit full thickness wound size reduction, sEVs release, angiogenesis, collagen arrangement | [77] |
Sr2+ loaded Na ALG aldehyde—polyetherimide (PEI) | Characterization, hydrogel self-healing behavior, in vitro cell response, cytotoxicity, rat wound healing | [78] |
Composition | Study Type/Target | Ref. |
---|---|---|
3.5% Na ALG—3% KCl—3.5% k-CG—3% CaCl2 Na ALG/k-CG weight ratio: 10:0, 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9, 0:10 | Characterization and thermostability | [80] |
ALG—k-CG ratio: 5:5, 7:3, 8:2 ALG—i-CG ratio: 5:5, 7:3, 8:2 | Formation and characterization; cytotoxicity, cell encapsulation | [73] |
3% w/v diclofenac—1–3% w/v Na CMC—0.5% w/v AlCl3 6H2O 3% w/v diclofenac—1–3% w/v Na ALG—5% w/v AlCl3 | Drug content and particle size, disintegration, friability and in vitro dissolution test, in vivo test on beagles | [50,81] |
Na ALG/k-CG %: 100, 75:25, 50:50, 25:75 + 0.125 g Fe3O4 | Hydrogel magnetic beads characterization, drug release, swelling | [82] |
2% w/v high M Na ALG—VEGF | In vitro drug analysis | [83] |
Beads of 1% Ca ALG—0.25% platelet lysate—0.03% vancomycin hydrochloride | Particle characterization, drug and PDGF AB release, PBS absorption, cell proliferation | [84] |
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Barbu, A.; Neamtu, B.; Zăhan, M.; Iancu, G.M.; Bacila, C.; Mireșan, V. Current Trends in Advanced Alginate-Based Wound Dressings for Chronic Wounds. J. Pers. Med. 2021, 11, 890. https://doi.org/10.3390/jpm11090890
Barbu A, Neamtu B, Zăhan M, Iancu GM, Bacila C, Mireșan V. Current Trends in Advanced Alginate-Based Wound Dressings for Chronic Wounds. Journal of Personalized Medicine. 2021; 11(9):890. https://doi.org/10.3390/jpm11090890
Chicago/Turabian StyleBarbu, Andreea, Bogdan Neamtu, Marius Zăhan, Gabriela Mariana Iancu, Ciprian Bacila, and Vioara Mireșan. 2021. "Current Trends in Advanced Alginate-Based Wound Dressings for Chronic Wounds" Journal of Personalized Medicine 11, no. 9: 890. https://doi.org/10.3390/jpm11090890