The production and application of hydrogels for wound management: A review

Abstract Wound treatment has increased in importance in the wound care sector due to the pervasiveness of chronic wounds in the high-risk population including, but not limited to, geriatric population, immunocompromised and obese patients. Furthermore, the number of people diagnosed with diabetes is rapidly growing. According to the World Health Organization (WHO), the global diabetic occurrence has increased from 4.7% in 1980 to 8.5% in 2014. As diabetes becomes a common medical condition, it has also become one of the major causes of chronic wounds which require specialised care to address patients’ unique needs. Wound dressings play a vital role in the wound healing process as they protect the wound site from the external environment. They are also capable of interacting with the wound bed in order to facilitate and accelerate the healing process. Advanced dressings such as hydrogels are designed to maintain a moist environment at the site of application and due to high water content are ideal candidates for wound management. Hydrogels can be used for both exudating or dry necrotic wounds. Additionally, hydrogels also demonstrate other unique features such as softness, malleability and biocompatibility. Nowadays, advanced wound care products make up around $7.1 billion of the global market and their production is growing at an annual rate of 8.3% with the market projected to be worth $12.5 billion by 2022. The presented review focuses on novel hydrogel wound dressings, their main characteristics and their wound management applications. It also describes recent methodologies used for their production and the future potential developments.

[1]  M. Ribeiro,et al.  Poly(vinyl alcohol)/chitosan asymmetrical membranes: Highly controlled morphology toward the ideal wound dressing , 2014 .

[2]  Nitesh Kumar,et al.  Flexible agar-sericin hydrogel film dressing for chronic wounds. , 2018, Carbohydrate polymers.

[3]  K. Pal,et al.  Polymeric Hydrogels: Characterization and Biomedical Applications , 2009 .

[4]  S. Han,et al.  Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: A phase III multicenter, double-blind, randomized, placebo-controlled trial. , 2018, Diabetes research and clinical practice.

[5]  Radim Hrdina,et al.  Chitin and chitosan from Brazilian Atlantic Coast: Isolation, characterization and antibacterial activity. , 2015, International journal of biological macromolecules.

[6]  S. Nair,et al.  Biomaterials based on chitin and chitosan in wound dressing applications. , 2011, Biotechnology advances.

[7]  H. Kapp,et al.  Clinical performance of a hydrogel dressing in chronic wounds: a prospective observational study. , 2007, Journal of wound care.

[8]  Liping Tang,et al.  Dual growth factor releasing multi-functional nanofibers for wound healing. , 2013, Acta biomaterialia.

[9]  Yinan Wang,et al.  Thermo-Responsive Poly(N-Isopropylacrylamide)-Cellulose Nanocrystals Hybrid Hydrogels for Wound Dressing , 2017, Polymers.

[10]  Rita Singh,et al.  Radiation synthesis of PVP/alginate hydrogel containing nanosilver as wound dressing , 2012, Journal of Materials Science: Materials in Medicine.

[11]  S. Bhang,et al.  Preparation and evaluation of visible-light cured glycol chitosan hydrogel dressing containing dual growth factors for accelerated wound healing , 2017 .

[12]  D. Kohane,et al.  HYDROGELS IN DRUG DELIVERY: PROGRESS AND CHALLENGES , 2008 .

[13]  Elbadawy A. Kamoun N-succinyl chitosan–dialdehyde starch hybrid hydrogels for biomedical applications , 2015, Journal of advanced research.

[14]  G. McGuinness,et al.  Absorbent polyvinyl alcohol–sodium carboxymethyl cellulose hydrogels for propolis delivery in wound healing applications , 2017 .

[15]  J. Torra i Bou,et al.  Open‐label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post‐operative surgical wounds , 2013, International wound journal.

[16]  M. Ribeiro,et al.  Thermoresponsive chitosan-agarose hydrogel for skin regeneration. , 2014, Carbohydrate polymers.

[17]  L. DiPietro,et al.  Factors Affecting Wound Healing , 2010, Journal of dental research.

[18]  S. Moreira,et al.  Bacterial Cellulose: Long-Term Biocompatibility Studies , 2012, Journal of biomaterials science. Polymer edition.

[19]  G. Ross,et al.  “Smart” carboxymethylchitosan hydrogels crosslinked with poly(N-isopropylacrylamide) and poly(acrylic acid) for controlled drug release , 2015 .

[20]  M. S. Lee,et al.  A β‐cyclodextrin, polyethyleneimine and silk fibroin hydrogel containing Centella asiatica extract and hydrocortisone acetate: releasing properties and in vivo efficacy for healing of pressure sores , 2012, Clinical and experimental dermatology.

[21]  Akalabya Bissoyi,et al.  Chitosan/TiO2 composite membrane improves proliferation and survival of L929 fibroblast cells: Application in wound dressing and skin regeneration. , 2017, International journal of biological macromolecules.

[22]  Kunal Pal,et al.  Starch Based Hydrogel with Potential Biomedical Application as Artificial Skin , 2009 .

[23]  E. Cosgriff-Hernandez,et al.  Chronic Wound Dressings Based on Collagen-Mimetic Proteins. , 2015, Advances in wound care.

[24]  B. Farrugia,et al.  Perlecan and vascular endothelial growth factor‐encoding DNA‐loaded chitosan scaffolds promote angiogenesis and wound healing , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[25]  Tao Wang,et al.  Hydrogel sheets of chitosan, honey and gelatin as burn wound dressings , 2012 .

[26]  J. Dutta,et al.  In vivo evaluation of chitosan-PVP-titanium dioxide nanocomposite as wound dressing material. , 2013, Carbohydrate polymers.

[27]  Hak Yong Kim,et al.  Wound-dressing materials with antibacterial activity from electrospun polyurethane-dextran nanofiber mats containing ciprofloxacin HCl. , 2012, Carbohydrate polymers.

[28]  C. Qing The molecular biology in wound healing & non-healing wound , 2017, Chinese journal of traumatology = Zhonghua chuang shang za zhi.

[29]  M. F. Akhtar,et al.  Methods of synthesis of hydrogels … A review , 2015, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[30]  Yudong Zheng,et al.  In situ synthesis of silver-nanoparticles/bacterial cellulose composites for slow-released antimicrobial wound dressing. , 2014, Carbohydrate polymers.

[31]  A. Rahal,et al.  Deferoxamine modulates cytokines and growth factors to accelerate cutaneous wound healing in diabetic rats. , 2015, European journal of pharmacology.

[32]  Jou‐Hyeon Ahn,et al.  Synthesis of acryloyl guar gum and its hydrogel materials for use in the slow release of L-DOPA and L-tyrosine , 2009 .

[33]  M. Arshad,et al.  Synthesis and evaluation of pH dependent polyethylene glycol-co-acrylic acid hydrogels for controlled release of venlafaxine HCl , 2018 .

[34]  Maurille J. Fournier,et al.  Protein engineering for materials applications , 1991 .

[35]  Ali Khademhosseini,et al.  Drug delivery systems and materials for wound healing applications. , 2018, Advanced drug delivery reviews.

[36]  Yitao Wang,et al.  In situ sequestration of endogenous PDGF-BB with an ECM-mimetic sponge for accelerated wound healing. , 2017, Biomaterials.

[37]  Wenxin Wang,et al.  Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer. , 2014, Acta biomaterialia.

[38]  V. Khutoryanskiy,et al.  Biomedical applications of hydrogels: A review of patents and commercial products , 2015 .

[39]  X. Xing,et al.  Covalently antibacterial alginate-chitosan hydrogel dressing integrated gelatin microspheres containing tetracycline hydrochloride for wound healing. , 2017, Materials science & engineering. C, Materials for biological applications.

[40]  A. Campos,et al.  The influence of growth factors on skin wound healing in rats , 2016, Brazilian journal of otorhinolaryngology.

[41]  Jennifer J. Kang-Mieler,et al.  Investigation of lysine acrylate containing poly(N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[42]  G. Fechine,et al.  Poly(N-vinyl-2-pyrrolidone) hydrogel production by ultraviolet radiation: new methodologies to accelerate crosslinking , 2004 .

[43]  M. Yarmush,et al.  Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice. , 2017, Biomaterials.

[44]  S. M. Taghdisi,et al.  Synthesis and preparation of biodegradable hybrid dextran hydrogel incorporated with biodegradable curcumin nanomicelles for full thickness wound healing. , 2017, International journal of pharmaceutics.

[45]  G. Tae,et al.  Epidermal growth factor loaded heparin-based hydrogel sheet for skin wound healing. , 2016, Carbohydrate polymers.

[46]  G. Palmese,et al.  The role of crystallization and phase separation in the formation of physically cross-linked PVA hydrogels , 2013 .

[47]  Stephanie Bryant,et al.  Degradable poly(2-hydroxyethyl methacrylate)-co-polycaprolactone hydrogels for tissue engineering scaffolds. , 2008, Biomacromolecules.

[48]  Werner Müller,et al.  Differential Roles of Macrophages in Diverse Phases of Skin Repair , 2010, The Journal of Immunology.

[49]  V. V. Shinde,et al.  Triple-crosslinkedβ-cyclodextrin oligomer self-healing hydrogel showing high mechanical strength, enhanced stability and pH responsiveness. , 2018, Carbohydrate polymers.

[50]  P. Sáha,et al.  On the characterization of sodium alginate/gelatine‐based hydrogels for wound dressing , 2012 .

[51]  P. Supaphol,et al.  Antimicrobial efficacy of a novel silver hydrogel dressing compared to two common silver burn wound dressings: Acticoat™ and PolyMem Silver(®). , 2014, Burns : journal of the International Society for Burn Injuries.

[52]  M. Gänzle,et al.  Effect of temperature on production of oligosaccharides and dextran by Weissella cibaria 10 M. , 2018, International journal of food microbiology.

[53]  M. Marquet,et al.  Genetic Engineering of Structural Protein Polymers , 1990, Biotechnology progress.

[54]  Ching-Nan Chuang,et al.  Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model. , 2013, Materials science & engineering. C, Materials for biological applications.

[55]  I. Uchegbu,et al.  Health economic burden that different wound types impose on the UK's National Health Service , 2017, International wound journal.

[56]  D. Levinson,et al.  Microbial cellulose wound dressing in the treatment of skin tears in the frail elderly. , 2010, Wounds : a compendium of clinical research and practice.

[57]  Anil Kumar Bajpai,et al.  Cryogenic fabrication of savlon loaded macroporous blends of alginate and polyvinyl alcohol (PVA). Swelling, deswelling and antibacterial behaviors , 2011 .

[58]  V. Álvarez,et al.  Poly(vinyl alcohol)/cellulose nanowhiskers nanocomposite hydrogels for potential wound dressings. , 2014, Materials science & engineering. C, Materials for biological applications.

[59]  Lei Tao,et al.  A novel poly(γ-glutamic acid)/silk-sericin hydrogel for wound dressing: Synthesis, characterization and biological evaluation. , 2015, Materials science & engineering. C, Materials for biological applications.

[60]  M. Walczak,et al.  Antimicrobial activity of collagen material with thymol addition for potential application as wound dressing , 2017 .

[61]  H. C. de Sousa,et al.  Recent advances on the development of wound dressings for diabetic foot ulcer treatment--a review. , 2013, Acta biomaterialia.

[62]  F. Meneau,et al.  Supramolecular poly(acrylic acid)/F127 hydrogel with hydration-controlled nitric oxide release for enhancing wound healing. , 2018, Acta biomaterialia.

[63]  F. Ungaro,et al.  Alginate-hyaluronan composite hydrogels accelerate wound healing process. , 2015, Carbohydrate polymers.

[64]  J. Pedraz,et al.  Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications. , 2017, International journal of pharmaceutics.

[65]  Hyoun‐Ee Kim,et al.  Polyurethane-silica hybrid foams from a one-step foaming reaction, coupled with a sol-gel process, for enhanced wound healing. , 2017, Materials science & engineering. C, Materials for biological applications.

[66]  J. Rosiak,et al.  Chitosan-containing hydrogel wound dressings prepared by radiation technique , 2017 .

[67]  E. Tredget,et al.  Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing. , 2016, Burns : journal of the International Society for Burn Injuries.

[68]  P. Datta,et al.  Accelerated healing of full thickness dermal wounds by macroporous waterborne polyurethane-chitosan hydrogel scaffolds. , 2017, Materials science & engineering. C, Materials for biological applications.

[69]  A. Karimi,et al.  Influence of Poly(acrylic acid) on the Mechanical Properties of Composite Hydrogels , 2015 .

[70]  S. Kalia,et al.  Guar gum based biodegradable, antibacterial and electrically conductive hydrogels. , 2015, International journal of biological macromolecules.

[71]  A. Chiriac,et al.  Synthesis of hydrogels based on poly(NIPAM) inserted into collagen sponge. , 2011, Colloids and surfaces. B, Biointerfaces.

[72]  Rúben Pereira,et al.  Development of novel alginate based hydrogel films for wound healing applications. , 2013, International journal of biological macromolecules.

[73]  Shiow-Fern Ng,et al.  Optimization, characterization, and in vitro assessment of alginate-pectin ionic cross-linked hydrogel film for wound dressing applications. , 2017, International journal of biological macromolecules.

[74]  Achim Goepferich,et al.  Hydrogel wound dressings for bioactive treatment of acute and chronic wounds , 2018 .

[75]  T. Abdelrahman,et al.  Wound dressings: principles and practice , 2011 .

[76]  Suneeta Kumari,et al.  Physicochemical properties and characterization of chitosan synthesized from fish scales, crab and shrimp shells. , 2017, International journal of biological macromolecules.

[77]  S. Britland,et al.  Characterisation and in vitro antimicrobial activity of biosynthetic silver-loaded bacterial cellulose hydrogels , 2016, Journal of microencapsulation.

[78]  Jian Li,et al.  High-efficiency production of bioactive oleosin-basic fibroblast growth factor in A. thaliana and evaluation of wound healing. , 2018, Gene.

[79]  G. Adamus,et al.  Bacterial-Derived Polymer Poly-γ-Glutamic Acid (γ-PGA)-Based Micro/Nanoparticles as a Delivery System for Antimicrobials and Other Biomedical Applications , 2017, International journal of molecular sciences.

[80]  Y. Nho,et al.  Gamma ray-induced synthesis of hyaluronic acid/chondroitin sulfate-based hydrogels for biomedical applications , 2015 .

[81]  Qingquan Liu,et al.  Fabrication and Physical Properties of Gelatin/Sodium Alginate/Hyaluronic Acid Composite Wound Dressing Hydrogel , 2014 .

[82]  Joydeep Dutta,et al.  Chitosan-PVP-nano silver oxide wound dressing: in vitro and in vivo evaluation. , 2015, International journal of biological macromolecules.

[83]  Hongbin Zhang,et al.  Physically crosslinked hydrogels from polysaccharides prepared by freeze–thaw technique , 2013 .

[84]  H. Horng,et al.  WOUND HEALING , 1969, Journal of the Chinese Medical Association : JCMA.

[85]  X. Qian,et al.  Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment. , 2014, International journal of pharmaceutics.

[86]  D. Philip Honey mediated green synthesis of silver nanoparticles. , 2009, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[87]  B. Obradovic,et al.  Synthesis and characterization of silver/poly(N-vinyl-2-pyrrolidone) hydrogel nanocomposite obtained by in situ radiolytic method , 2011 .

[88]  Giriprasath Ramanathan,et al.  In vivo efficiency of the collagen coated nanofibrous scaffold and their effect on growth factors and pro‐inflammatory cytokines in wound healing , 2017, European journal of pharmacology.

[89]  C. Dwivedi,et al.  Silver nanoparticle-loaded PVA/gum acacia hydrogel: synthesis, characterization and antibacterial study. , 2012, Carbohydrate polymers.

[90]  Baljit Singh,et al.  Radiation crosslinking polymerization of sterculia polysaccharide-PVA-PVP for making hydrogel wound dressings. , 2011, International journal of biological macromolecules.

[91]  M. Giretzlehner,et al.  The properties of an "ideal" burn wound dressing--what do we need in daily clinical practice? Results of a worldwide online survey among burn care specialists. , 2012, Burns : journal of the International Society for Burn Injuries.

[92]  박상민,et al.  탄소원에 따른 Bacterial Cellulose의 물성 , 2010 .

[93]  G. Schultz,et al.  Interactions between extracellular matrix and growth factors in wound healing , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[94]  Xian Xu,et al.  Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex Networks. , 2012, Soft matter.

[95]  A. Kamali,et al.  The concurrent use of probiotic microorganism and collagen hydrogel/scaffold enhances burn wound healing: An in vivo evaluation. , 2018, Burns : journal of the International Society for Burn Injuries.

[96]  M. Kokabi,et al.  PVA–clay nanocomposite hydrogels for wound dressing , 2007 .

[97]  N. Škalko-Basnet,et al.  Beta‐glucan‐loaded nanofiber dressing improves wound healing in diabetic mice , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[98]  A. Bhat,et al.  Poly-γ-glutamic acid: production, properties and applications. , 2015, Microbiology.

[99]  X. Qin,et al.  Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study. , 2018, Acta biomaterialia.

[100]  R. de Bree,et al.  Randomized clinical trial of donor‐site wound dressings after split‐skin grafting , 2013, The British journal of surgery.

[101]  A. Onjia,et al.  Physical-chemical behavior of novel copolymers composed of methacrylic acid and 2-acrylamido-2-methylpropane sulfonic acid , 2016 .

[102]  C. van Nostrum,et al.  Novel crosslinking methods to design hydrogels. , 2002, Advanced drug delivery reviews.

[103]  M. Nie,et al.  Preparation and characterization of aminated hyaluronic acid/oxidized hydroxyethyl cellulose hydrogel. , 2018, Carbohydrate polymers.

[104]  Manuel Arruebo,et al.  Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds , 2015, Materials.

[105]  R. Simman,et al.  Modern collagen wound dressings: function and purpose. , 2010, The journal of the American College of Certified Wound Specialists.

[106]  J. Leach,et al.  Synthesis and Characterization of Carboxymethylcellulose-Methacrylate Hydrogel Cell Scaffolds. , 2010, Polymers.

[107]  Alessandro Sannino,et al.  Polymeric hydrogels for burn wound care: Advanced skin wound dressings and regenerative templates , 2014, Burns & Trauma.

[108]  J. Timmons,et al.  Aquaform ® hydrogel — a new formulation for an improved wound care performance , 2008 .

[109]  Michael Landthaler,et al.  Cytokines, chemokines and growth factors in wound healing , 2012, Journal of the European Academy of Dermatology and Venereology : JEADV.

[110]  A. Jayakrishnan,et al.  Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. , 2005, Biomaterials.

[111]  Jing Peng,et al.  Radiation synthesis of PVP/CMC hydrogels as wound dressing , 2007 .

[112]  A. Mansur,et al.  Superabsorbent crosslinked carboxymethyl cellulose-PEG hydrogels for potential wound dressing applications. , 2018, International journal of biological macromolecules.

[113]  D. Hoefer,et al.  Biotechnologically produced microbial alginate dressings show enhanced gel forming capacity compared to commercial alginate dressings of marine origin , 2015, Journal of Materials Science: Materials in Medicine.

[114]  Wenxin Wang,et al.  A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing. , 2018, Acta biomaterialia.

[115]  I. Banerjee,et al.  Guar gum and sesame oil based novel bigels for controlled drug delivery. , 2014, Colloids and surfaces. B, Biointerfaces.

[116]  Manisha Pandey,et al.  Microwaved bacterial cellulose-based hydrogel microparticles for the healing of partial thickness burn wounds , 2017, Drug Delivery and Translational Research.

[117]  R. Reis,et al.  Stem Cell-Containing Hyaluronic Acid-Based Spongy Hydrogels for Integrated Diabetic Wound Healing. , 2017, The Journal of investigative dermatology.

[118]  Zhijun Shi,et al.  A transparent wound dressing based on bacterial cellulose whisker and poly(2-hydroxyethyl methacrylate). , 2017, International journal of biological macromolecules.

[119]  H. Schönherr,et al.  Amphiphilic Block Copolymer Vesicles for Active Wound Dressings: Synthesis of Model Systems and Studies of Encapsulation and Release , 2013 .

[120]  H. Kafil,et al.  Antibiotic loaded carboxymethylcellulose/MCM-41 nanocomposite hydrogel films as potential wound dressing. , 2016, International journal of biological macromolecules.

[121]  Zulkifli Ahmad,et al.  Classification, processing and application of hydrogels: A review. , 2015, Materials science & engineering. C, Materials for biological applications.

[122]  J. Maitra,et al.  Cross-linking in Hydrogels - A Review , 2014 .

[123]  M. Taher,et al.  PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization , 2018, Pharmaceutical development and technology.

[124]  R. Soares,et al.  Studies on the hemocompatibility of bacterial cellulose. , 2011, Journal of biomedical materials research. Part A.

[125]  N. Gabilondo,et al.  Synthesis of stimuli-responsive chitosan-based hydrogels by Diels-Alder cross-linking `click´ reaction as potential carriers for drug administration. , 2018, Carbohydrate polymers.

[126]  Thawatchai Maneerung,et al.  Impregnation of silver nanoparticles into bacterial cellulose for antimicrobial wound dressing , 2008 .

[127]  J. Kelly,et al.  Hydrocolloid dressing in pediatric burns may decrease operative intervention rates. , 2010, Journal of pediatric surgery.

[128]  Olivera Stojadinovic,et al.  PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[129]  H. Namazi,et al.  A potential bioactive wound dressing based on carboxymethyl cellulose/ZnO impregnated MCM-41 nanocomposite hydrogel. , 2017, Materials science & engineering. C, Materials for biological applications.

[130]  Deok-Won Lee,et al.  Visible light-cured glycol chitosan hydrogel dressing containing endothelial growth factor and basic fibroblast growth factor accelerates wound healing in vivo , 2018, Journal of Industrial and Engineering Chemistry.

[131]  S. Britland,et al.  Physicochemical characterisation of biosynthetic bacterial cellulose as a potential wound dressing material , 2018, British Journal of Pharmacy.

[132]  A. Bajpai,et al.  Evaluation of poly (vinyl alcohol) based cryogel-zinc oxide nanocomposites for possible applications as wound dressing materials. , 2016, Materials science & engineering. C, Materials for biological applications.

[133]  G. Winter,et al.  Formation of the Scab and the Rate of Epithelization of Superficial Wounds in the Skin of the Young Domestic Pig , 1962, Nature.

[134]  M. Amin,et al.  Current trends in the development of wound dressings, biomaterials and devices. , 2013, Pharmaceutical patent analyst.

[135]  R. Reis,et al.  Preparation of barley and yeast β-glucan scaffolds by hydrogel foaming: evaluation of dexamethasone release , 2017 .

[136]  H. C. de Sousa,et al.  Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice. , 2014, Biochimica et biophysica acta.

[137]  Bimetallic alginate nanocomposites: New antimicrobial biomaterials for biomedical application , 2018 .

[138]  A. Palmer,et al.  The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes , 2018, Front. Physiol..

[139]  A. Domb,et al.  Microparticulate polymers and hydrogels for wound healing , 2016 .

[140]  M. Flanagan Wound Healing and Skin Integrity: Principles and Practice , 2013 .

[141]  T. Higashi,et al.  Physically crosslinked-sacran hydrogel films for wound dressing application. , 2016, International journal of biological macromolecules.

[142]  P. Supaphol,et al.  Silver nanoparticles-based hydrogel: Characterization of material parameters for pressure ulcer dressing applications , 2018 .

[143]  S. Hsu,et al.  Synthesis of Thermoresponsive Amphiphilic Polyurethane Gel as a New Cell Printing Material near Body Temperature. , 2015, ACS applied materials & interfaces.

[144]  Seung-Kyu Han,et al.  Basics of Wound Healing , 2016 .

[145]  Yingyu Zhou,et al.  Radiation synthesis and characterization of nanosilver/gelatin/carboxymethyl chitosan hydrogel , 2012 .

[146]  H. Larjava,et al.  Cell and Molecular Biology of Wound Healing , 2015 .

[147]  Louise E Smith,et al.  A history of materials and practices for wound management , 2012 .

[148]  Paul G Scott,et al.  Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis , 2007, Stem cells.

[149]  Design and Preparation of Synthetic Hydrogels by Redox Initiation via Free Radical Polymerisation for Biomedical Use as Wound Dressings , 2012 .

[150]  S. MacNeil,et al.  Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin. , 2011, Biomaterials.

[151]  Zhen-Zhong Xu,et al.  TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: Distinct role of TNF receptor subtypes 1 and 2 , 2011, PAIN®.

[152]  M. B. El-Arnaouty,et al.  Radiation synthesis of superabsorbent CMC based hydrogels for agriculture applications , 2012 .

[153]  Yan Zhao,et al.  Restraint stress alters neutrophil and macrophage phenotypes during wound healing , 2013, Brain, Behavior, and Immunity.

[154]  D. Petri,et al.  Microbicidal gentamicin-alginate hydrogels. , 2018, Carbohydrate polymers.

[155]  Min Zhang,et al.  Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing , 2015, Scientific Reports.

[156]  Arijit Ghosh,et al.  Development and characterization of chitosan-based hydrogels as wound dressing materials , 2018, Journal of Drug Delivery Science and Technology.

[157]  Xiaoxiang Zheng,et al.  Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds. , 2013, Acta biomaterialia.

[158]  Glyn O. Phillips,et al.  Hydrogels: Methods of Preparation, Characterisation and Applications , 2011 .

[159]  D. Levinson,et al.  Microbial cellulose wound dressing in the treatment of nonhealing lower extremity ulcers. , 2009, Wounds : a compendium of clinical research and practice.

[160]  S. Raj,et al.  Green synthesis and characterization of silver nanoparticles using Enicostemma axillare (Lam.) leaf extract. , 2018, Biochemical and biophysical research communications.

[161]  T. Phillips,et al.  Wound healing and treating wounds: Differential diagnosis and evaluation of chronic wounds. , 2016, Journal of the American Academy of Dermatology.

[162]  Y. Tokura,et al.  Attempts to accelerate wound healing. , 2014, Journal of dermatological science.

[163]  S. Hampel,et al.  Carbon nanotubes hybrid hydrogels for electrically tunable release of Curcumin , 2017 .

[164]  J. Lee,et al.  Gentamicin-Loaded Wound Dressing With Polyvinyl Alcohol/Dextran Hydrogel: Gel Characterization and In Vivo Healing Evaluation , 2010, AAPS PharmSciTech.

[165]  Nollapan Nootsuwan,et al.  Preparation of PVP/MHEC Blended Hydrogels via Gamma Irradiation and Their Calcium ion Uptaking and Releasing Ability , 2013 .

[166]  E. Manias,et al.  A randomised controlled trial of the effectiveness of soft silicone multi‐layered foam dressings in the prevention of sacral and heel pressure ulcers in trauma and critically ill patients: the border trial , 2015, International wound journal.

[167]  M. Henriques,et al.  Cyclodextrin-based hydrogels toward improved wound dressings , 2014, Critical reviews in biotechnology.

[168]  Deng-yong Hou,et al.  Preparation of chitosan-collagen-alginate composite dressing and its promoting effects on wound healing. , 2018, International journal of biological macromolecules.

[169]  J. Simal-Gándara,et al.  Encapsulation of yarrow essential oil in hydroxypropyl-beta-cyclodextrin: physiochemical characterization and evaluation of bio-efficacies , 2017 .

[170]  Muhammad Mustafa Abeer,et al.  A review of bacterial cellulose‐based drug delivery systems: their biochemistry, current approaches and future prospects , 2014, The Journal of pharmacy and pharmacology.

[171]  Senem Coşkun,et al.  Synthesis, characterization and in vitro antimicrobial activities of boron/starch/polyvinyl alcohol hydrogels , 2011 .

[172]  J. Kost,et al.  Characterization and antimicrobial activity of silver nanoparticles, biosynthesized using Bacillus species , 2017 .

[173]  Pornanong Aramwit,et al.  An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing. , 2012, International journal of pharmaceutics.

[174]  Lanlan Liu,et al.  Formation and characterization of silver nanoparticles in aqueous solution via ultrasonic irradiation. , 2014, Ultrasonics sonochemistry.

[175]  Jennifer G Powers,et al.  Wound healing and treating wounds: Chronic wound care and management. , 2016, Journal of the American Academy of Dermatology.

[176]  B. Gupta,et al.  Preparation and characterization of in-situ crosslinked pectin-gelatin hydrogels. , 2014, Carbohydrate polymers.

[177]  Abhinav Mehta,et al.  Stimuli-responsive hydrogels in drug delivery and tissue engineering , 2016, Drug delivery.

[178]  R. Molloy,et al.  Structural effects in photopolymerized sodium AMPS hydrogels crosslinked with poly(ethylene glycol) diacrylate for use as burn dressings , 2013, Journal of biomaterials science. Polymer edition.

[179]  Lihong Fan,et al.  Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings. , 2016, Carbohydrate polymers.

[180]  M. Taya,et al.  Polyvinyl alcohol-based hydrogel dressing gellable on-wound via a co-enzymatic reaction triggered by glucose in the wound exudate. , 2013, Journal of materials chemistry. B.

[181]  E. Kenawy,et al.  Physically crosslinked poly(vinyl alcohol)-hydroxyethyl starch blend hydrogel membranes: Synthesis and characterization for biomedical applications , 2014 .

[182]  A. Zamanian,et al.  Preparation and characterization of in situ chitosan/polyethylene glycol fumarate/thymol hydrogel as an effective wound dressing. , 2017, Materials science & engineering. C, Materials for biological applications.

[183]  J. Filipović,et al.  Smart poly(2-hydroxyethyl methacrylate/itaconic acid) hydrogels for biomedical application , 2010 .

[184]  C. R. Pereira,et al.  Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization , 2016, Molecules.

[185]  Zibiao Li,et al.  Towards the development of polycaprolactone based amphiphilic block copolymers: molecular design, self-assembly and biomedical applications. , 2014, Materials science & engineering. C, Materials for biological applications.

[186]  R. Zhuo,et al.  Amphiphilic Block‐Graft Copolymers Poly(ethylene glycol)‐b‐(polycarbonates‐g‐palmitate) Prepared via the Combination of Ring‐Opening Polymerization and Click Chemistry , 2012 .

[187]  G. Schroeder,et al.  Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing , 2017, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[188]  T. Koh,et al.  Inflammation and wound healing: the role of the macrophage , 2011, Expert Reviews in Molecular Medicine.

[189]  G. McGuinness,et al.  Properties of PVA Hydrogel Wound-Care Dressings Containing UK Propolis , 2016 .

[190]  G. Toríz,et al.  Rheological characterization of new thermosensitive hydrogels formed by chitosan, glycerophosphate, and phosphorylated β-cyclodextrin. , 2018, Carbohydrate polymers.

[191]  S. Pacelli,et al.  Injectable and photocross-linkable gels based on gellan gum methacrylate: a new tool for biomedical application. , 2015, International journal of biological macromolecules.

[192]  A. Goepferich,et al.  pH-Modulating Poly(ethylene glycol)/Alginate Hydrogel Dressings for the Treatment of Chronic Wounds. , 2017, Macromolecular bioscience.

[193]  E. Kenawy,et al.  Poly (vinyl alcohol)-alginate physically crosslinked hydrogel membranes for wound dressing applications: Characterization and bio-evaluation , 2015 .

[194]  H. Kono,et al.  Preparation and characterization of guar gum hydrogels as carrier materials for controlled protein drug delivery. , 2014, Carbohydrate polymers.

[195]  C. Witthayaprapakorn Design and Preparation of Synthetic Hydrogels Via Photopolymerisation for Biomedical Use as Wound Dressings , 2011 .

[196]  M. Landthaler,et al.  Wound healing in the 21st century. , 2010, Journal of the American Academy of Dermatology.

[197]  Enas M. Ahmed,et al.  Hydrogel: Preparation, characterization, and applications: A review , 2013, Journal of advanced research.

[198]  K. Cutting,et al.  Clinical evaluation of a bioactive beta-glucan gel in the treatment of 'hard-to-heal' wounds. , 2017, Journal of wound care.

[199]  Armando J D Silvestre,et al.  Bacterial cellulose membranes applied in topical and transdermal delivery of lidocaine hydrochloride and ibuprofen: in vitro diffusion studies. , 2012, International journal of pharmaceutics.

[200]  Ming-Chien Yang,et al.  Acceleration of wound healing in diabetic rats by layered hydrogel dressing , 2012 .

[201]  Baljit Singh,et al.  Designing bio-mimetic moxifloxacin loaded hydrogel wound dressing to improve antioxidant and pharmacology properties , 2015 .

[202]  Jhamak Nourmohammadi,et al.  The antibacterial and anti-inflammatory investigation of Lawsonia Inermis-gelatin-starch nano-fibrous dressing in burn wound. , 2018, International journal of biological macromolecules.

[203]  S. Varghese,et al.  Hydrogels: a versatile tool with a myriad of biomedical and research applications for the skin , 2012 .

[204]  C Torrance,et al.  The physiology of wound healing. , 1986, Nursing.

[205]  A. Di Rienzo,et al.  Thermosensitive block copolymer hydrogels based on poly(ɛ-caprolactone) and polyethylene glycol for biomedical applications: state of the art and future perspectives. , 2015, Journal of biomedical materials research. Part A.

[206]  Hongbin Li,et al.  Hydrogels Constructed from Engineered Proteins. , 2016, Small.

[207]  Shufang Wang,et al.  A composite hydrogel of chitosan/heparin/poly (γ-glutamic acid) loaded with superoxide dismutase for wound healing. , 2018, Carbohydrate polymers.

[208]  K. Bratlie,et al.  pH sensitive methacrylated chitosan hydrogels with tunable physical and chemical properties , 2018 .

[209]  Sharon Gerecht,et al.  Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing , 2011, Proceedings of the National Academy of Sciences.

[210]  M. Khil,et al.  Preparation and evaluation of β-glucan hydrogel prepared by the radiation technique for drug carrier applications. , 2018, International journal of biological macromolecules.

[211]  Huifang Zhou,et al.  In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration , 2016 .

[212]  E. Kaditi,et al.  Amphiphilic block copolymers by a combination of anionic polymerization and selective post-polymerization functionalization , 2011 .

[213]  Jingjing Wang,et al.  Interpenetrating network hydrogels with high strength and transparency for potential use as external dressings. , 2017, Materials science & engineering. C, Materials for biological applications.

[214]  R. Steinhardt,et al.  Characterization of pHEMA-based hydrogels that exhibit light-induced bactericidal effect via release of NO , 2009, Journal of materials science. Materials in medicine.

[215]  V. John,et al.  Development and characterization of a novel, antimicrobial, sterile hydrogel dressing for burn wounds: single-step production with gamma irradiation creates silver nanoparticles and radical polymerization. , 2014, Journal of pharmaceutical sciences.

[216]  T. K. Hunt,et al.  Physiology of wound healing. , 2000, Advances in skin & wound care.

[217]  Donghong Liu,et al.  Formation of hydrogels based on chitosan/alginate for the delivery of lysozyme and their antibacterial activity. , 2018, Food chemistry.

[218]  Jennifer Gloeckner Powers,et al.  Dressings for chronic wounds , 2013, Dermatologic therapy.

[219]  Feng F. Hong,et al.  Preparation and evaluation of a kind of bacterial cellulose dry films with antibacterial properties , 2011 .

[220]  A. Nyström,et al.  The role of TGFβ in wound healing pathologies , 2017, Mechanisms of Ageing and Development.

[221]  H. Yeganeh,et al.  Preparation of antimicrobial wound dressings via thiol–ene photopolymerization reaction , 2018, Journal of Materials Science.

[222]  Yoorim Choi,et al.  Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing. , 2016, Acta biomaterialia.

[223]  Ayse Sezer Hicyilmaz,et al.  Synthesis, characterization and chlorination of 2-acrylamido-2-methylpropane sulfonic acid sodium salt-based antibacterial hydrogels , 2017 .

[224]  Tomaz Velnar,et al.  The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms , 2009, The Journal of international medical research.

[225]  J. Yang,et al.  Superabsorbent polysaccharide hydrogels based on pullulan derivate as antibacterial release wound dressing. , 2011, Journal of biomedical materials research. Part A.

[226]  J. Rosiak,et al.  Radiation synthesis of biocompatible hydrogels of dextran methacrylate , 2018 .

[227]  Ilídio J Correia,et al.  Development of a new chitosan hydrogel for wound dressing , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[228]  April M. Kloxin,et al.  Thiol-ene click hydrogels for therapeutic delivery. , 2016, ACS biomaterials science & engineering.

[229]  Jan Szopa,et al.  The local treatment and available dressings designed for chronic wounds. , 2013, Journal of the American Academy of Dermatology.