Medicine:Hydrogel dressing

From HandWiki

Hydrogels are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers.[1] The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing.[2] Hydrogel dressings can be designed to prevent bacterial infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility.[1][2] Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed.[3] Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.[2][4]

Hydrogels respond elastically to applied stress; gels made from materials like collagen exhibit high toughness and low sliding friction, reducing damage from mechanical stress.[1][5] Hydrogel dressings should possess mechanical and physical properties similar to the 3D microenvironment of the extracellular matrix of human skin.[6] Hydrogel wound dressings are designed to have a mechanism for application and removal which minimizes further trauma to tissues.[1]

Hydrogel dressings can be sorted into the categories: synthetic, natural, and hybrid.[1] Synthetic hydrogel dressings have been produced using biomimetic extracellular matrix nanofibers such as polyvinyl alcohol (PVA).[7] Self-assembling designer peptide hydrogels are another type of synthetic hydrogel in development.[8] Natural hydrogel dressings are further subdivided into either polysaccharide-based (e.g. alginates) or proteoglycan- and/or protein-based (e.g. collagen).[7] Hybrid hydrogel dressings incorporate synthetic nanoparticles and natural materials.[2]

Characteristics

Chemical characteristics

Hydrogel dressings exhibit chemical or physical cross-linking. Chemical cross-linking involved formation of covalent bonds between polymer chains. Chemically cross-linked hydrogel dressings are synthesized by chain-growth polymerization, step-growth polymerization, enzymes, or irradiation polymerization.[citation needed] Synthetic dressings incorporating nanoparticles such as PVA and polyethylene glycol (PEG) are assembled using chemical cross-linking mechanisms.[9][10] Physically cross-linked hydrogel dressings are assembled via ionic interaction, hydrogen bonding, hydrophobic interactions, or crystallization.[citation needed] Physically cross-linked hydrogels disintegrate due to local changes in pH, ionic strength, and temperature.[3] Natural dressings incorporating polysaccharides and proteoglycans/proteins form a 3D network using physical cross-linking.[11] Hydrogel dressings mimic the cross-linked 3D network of extracellular matrix fibers in human skin.[1]

Hydrogels can be formed through a self-assembly process in which monomers diffuse in solution then form non covalent interactions.[citation needed] Hydrogels used in wound dressings can be self-assembled upon addition of divalent metal cations or electrically charged polysaccharides due to electrostatic interactions.[12][13] Self-assembly via hydrophobic interactions can be induced in amphiphilic polysaccharides-based gels by addition of water; it can also be induced in non amphiphilic polysaccharide-based hydrogels by addition of hydrophobic grafts.[8][12]

Cross-linking of soluble hydrophilic monomers forms a 3D insoluble netted structure which can incorporate a large amount of water.[14] The 3D polymeric network of hydrogels is highly hydrated with 90-99% water w/w; it is capable of binding many times more water molecules when assembled than in the uncross-linked state.[2][3] Hydrogel dressings can absorb up to 600 times their initial amount of water, including fluid-based wound exudates.[2][14] Hydrogels are effective biomaterials for wound dressings and tissue engineering because they exchange fluid, hydrating necrotic tissues.[2][6] The absorption of secretions causes the hydrogel dressing to swell, expanding the cross links in the polymer chains.[6] The expanded 3D cross-linked network can irreversibly incorporate pathogens and detritus, thereby removing them from the wound.[6]

Some hydrogel dressings have intrinsic antimicrobial properties. Hydrogel dressings formed from antimicrobial peptides (AMPs) and chitosan have inherent antimicrobial activity.[15][16][17] The antimicrobial properties of hydrogel dressings can be enhanced by addition of metal nanoparticles, antibiotics, or other antimicrobial agents.[15][18][19][20] Silver and gold nanoparticles can also be incorporated into hydrogel dressings to enhance antimicrobial activity.[15] Some hydrogel dressings have antibiotics such as ciprofloxacin and amoxicillin incorporated into their structure which are unloaded into the wound as fluid is exchanged.[15][19] Some hydrogel dressings have incorporated stimuli-responsive nitric oxide-releasing agents and other antimicrobial agents.[15][20]

Hydrogel dressings can adhere directly to the wound bed under normal physiological conditions via oxidation-reduction reactions of quinones.[2][21] The adhesive properties of hydrogels have been shown to be enhanced by addition of positively charged microgels (MR) into the 3D matrix to increase electrostatic and hydrophobic interactions.[22]

Physical characteristics

Wound dressings should be stretchable to prevent tearing. Hai Lei et al. demonstrated that poor elasticity and hysteresis in naturally-derived protein-based hydrogels can be remedied by the addition of polyprotein cross-linkers.[23] The flexibility of hydrogels can also be enhanced by incorporating microgels into the matrix.[22][24] Hydrogel dressings mimic the fibrous nature of native ECM to maintain cell-to-cell communication at the wound bed for tissue regeneration.[24]

Self-healing hydrogels automatically and reversibly repair damage done due to mechanical and chemical stress.[25] Self-healing mechanisms can involve "dynamic covalent bonding, non-covalent interactions" and mixed interactions.[25] Covalent interactions involved in self-healing include Schiff base formation and disulfide exchange.[25] Non-covalent interactions are generally less stable and make the hydrogel more sensitive to microenvironmental changes (e.g. pH, temperature).[25] Some hydrogel dressings are self-healing due to mixed mechanisms such as host-guest and protein-ligand interactions.[25]

Hydrogel dressings are available in sheet, amorphous, impregnated, or sprayable forms.[15][26][27][28][29] Sheet-form hydrogel dressings are non-adhesive against the wound and are effective in healing partial-thickness wounds.[26] Amorphous hydrogels are more effective in treatment of full-thickness wounds than sheet-form dressings because they can conform to the shape of the wound bed and they facilitate autolytic debridement.[27] Impregnated hydrogel dressings are dry dressings (e.g. gauzes) saturated with an amorphous hydrogel.[28] Sprayable hydrogel dressings are composed of amorphous hydrogels which rapidly increase in viscosity after application.[29] Sprayable hydrogels have also been shown to increase the penetration and efficacy of therapeutic agents.[2]

"Smart" hydrogel dressings

"Smart" hydrogels which are stimuli-responsive (i.e. thermoresponsive, bioresponsive, pH-responsive, photoresponsive, and redox-responsive) are also being produced.[3] pH-responsive hydrogel dressings which release growth factors and antibiotic agents as the pH of the wound increases from normal skin levels (pH 4–6) to internal levels (pH ~7.4).[30] Redox-responsive hydrogel dressings can be disintegrated on-demand by addition of a reducing agent.[31] Assembly of the 3D network of photoresponsive hydrogel dressings is initiated by UV radiation.[32] Thermoresponsive hydrogel dressings which exhibit temperature-dependent sol-gel transition and/or temperature-dependent drug release.[33][34]

Applications

The efficacy of hydrogel dressings has been assessed on various wound types. There is some evidence to suggest that hydrogels are effective dressings for chronic wounds including pressure ulcers, diabetic ulcers, and venous ulcers although the results are uncertain.[35][36][37][38] Hydrogels have been shown to accelerate healing in partial and full thickness burn wounds of varying size.[39][40][41] Other studies have shown that hydrogel dressings accelerate healing in radioactive skin injuries and dog bite wounds.[42][43][44] Hydrogel dressings decrease the healing time of traumatic skin injuries by an average 5.28 days and reduce the pain reported by patients.[42][45][46]

Types

Naturally-derived hydrogel dressings

Polysaccharide-based hydrogel dressings have been synthesized from polymers such as hyaluronic acid, chitin, chitosan, alginate, and agarose.[1][40][47][48][49] Naturally-derived protein/proteoglycan hydrogel dressings have been synthesized from polymers such as collagen, gelatin, kappa-carrageenan, and fibrin.[1][49][50][51]  

Synthetic hydrogel dressings

Synthetic hydrogel dressings may be derived from synthetic polymers such as polyvinyl alcohol (PVA), poly(ethylene glycol) (PEG), polyurethane (PU), and poly(lactide-co-glycolide) (PLGA).[1][52][53] Synthetic hydrogel dressings may also be formed from designer peptides.[8][54] Researchers are applying 3D printing to the synthesis of hydrogel dressings.[55][56]

Biohybrid hydrogel dressings

Hydrogels may be modified to incorporate metal cations (e.g. copper (II)), degradable linkers (e.g. dextran), and adhesive functional groups (e.g. RGD).[1] Integrating biological derivatives into synthetic hydrogels allows producers to tailor binding affinities and specificity, mechanical properties, and stimuli-responsive properties.[1]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Peppas, N. A.; Hilt, J. Z.; Khademhosseini, A.; Langer, R. (2006-06-06). "Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology" (in en). Advanced Materials 18 (11): 1345–1360. doi:10.1002/adma.200501612. ISSN 0935-9648. Bibcode: 2006AdM....18.1345P. https://onlinelibrary.wiley.com/doi/10.1002/adma.200501612. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Tavakoli, Shima; Klar, Agnes S. (2020-08-11). "Advanced Hydrogels as Wound Dressings" (in en). Biomolecules 10 (8): 1169. doi:10.3390/biom10081169. ISSN 2218-273X. PMID 32796593. 
  3. ↑ 3.0 3.1 3.2 3.3 Ulijn, Rein V.; Bibi, Nurguse; Jayawarna, Vineetha; Thornton, Paul D.; Todd, Simon J.; Mart, Robert J.; Smith, Andrew M.; Gough, Julie E. (April 2007). "Bioresponsive hydrogels" (in en). Materials Today 10 (4): 40–48. doi:10.1016/S1369-7021(07)70049-4. 
  4. ↑ Percival, Steven L.; McCarty, Sara; Hunt, John A.; Woods, Emma J. (2014-02-24). "The effects of pH on wound healing, biofilms, and antimicrobial efficacy". Wound Repair and Regeneration 22 (2): 174–186. doi:10.1111/wrr.12125. ISSN 1067-1927. PMID 24611980. 
  5. ↑ Xu, Cancan; Dai, Guohao; Hong, Yi (September 2019). "Recent advances in high-strength and elastic hydrogels for 3D printing in biomedical applications" (in en). Acta Biomaterialia 95: 50–59. doi:10.1016/j.actbio.2019.05.032. PMID 31125728. 
  6. ↑ 6.0 6.1 6.2 6.3 Jones, Annie; Vaughan, David (December 2005). "Hydrogel dressings in the management of a variety of wound types: A review" (in en). Journal of Orthopaedic Nursing 9: S1–S11. doi:10.1016/S1361-3111(05)80001-9. https://linkinghub.elsevier.com/retrieve/pii/S1361311105800019. 
  7. ↑ 7.0 7.1 Mogoşanu, George Dan; Grumezescu, Alexandru Mihai (March 2014). "Natural and synthetic polymers for wounds and burns dressing" (in en). International Journal of Pharmaceutics 463 (2): 127–136. doi:10.1016/j.ijpharm.2013.12.015. PMID 24368109. https://linkinghub.elsevier.com/retrieve/pii/S0378517313010831. 
  8. ↑ 8.0 8.1 8.2 Rivas, Manuel; del Valle, Luís; Alemán, Carlos; Puiggalí, Jordi (2019-03-06). "Peptide Self-Assembly into Hydrogels for Biomedical Applications Related to Hydroxyapatite" (in en). Gels 5 (1): 14. doi:10.3390/gels5010014. ISSN 2310-2861. PMID 30845674. 
  9. ↑ Varshney, Lalit (February 2007). "Role of natural polysaccharides in radiation formation of PVA–hydrogel wound dressing". Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 255 (2): 343–349. doi:10.1016/j.nimb.2006.11.101. ISSN 0168-583X. Bibcode: 2007NIMPB.255..343V. http://dx.doi.org/10.1016/j.nimb.2006.11.101. 
  10. ↑ Kasko, Andrea M. "Degradable Poly(ethylene glycol) Hydrogels for 2D and 3D Cell Culture". https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/materials-science-and-engineering/tissue-engineering/degradable-polyethylene-glycol-hydrogels. 
  11. ↑ Hennink, W.E; van Nostrum, C.F (January 2002). "Novel crosslinking methods to design hydrogels". Advanced Drug Delivery Reviews 54 (1): 13–36. doi:10.1016/s0169-409x(01)00240-x. ISSN 0169-409X. PMID 11755704. http://dx.doi.org/10.1016/s0169-409x(01)00240-x. 
  12. ↑ 12.0 12.1 Gonçalves, Catarina; Pereira, Paula; Gama, Miguel (2010-02-24). "Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications". Materials 3 (2): 1420–1460. doi:10.3390/ma3021420. ISSN 1996-1944. Bibcode: 2010Mate....3.1420G. 
  13. ↑ Basak, Shibaji; Nanda, Jayanta; Banerjee, Arindam (2014). "Multi-stimuli responsive self-healing metallo-hydrogels: tuning of the gel recovery property". Chem. Commun. 50 (18): 2356–2359. doi:10.1039/c3cc48896a. ISSN 1359-7345. PMID 24448590. http://dx.doi.org/10.1039/c3cc48896a. 
  14. ↑ 14.0 14.1 Wong, Vicky (2007). "Hydrogels". Catalyst: 18–21. https://www.stem.org.uk/system/files/elibrary-resources/legacy_files_migrated/8567-catalyst_18_1_335.pdf.. 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 Salomé Veiga, Ana; Schneider, Joel P. (November 2013). "Antimicrobial hydrogels for the treatment of infection". Biopolymers 100 (6): 637–644. doi:10.1002/bip.22412. ISSN 0006-3525. PMID 24122459. PMC 3929057. http://dx.doi.org/10.1002/bip.22412. 
  16. ↑ Chan, David I.; Prenner, Elmar J.; Vogel, Hans J. (September 2006). "Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action". Biochimica et Biophysica Acta (BBA) - Biomembranes 1758 (9): 1184–1202. doi:10.1016/j.bbamem.2006.04.006. ISSN 0005-2736. PMID 16756942. 
  17. ↑ Park, Bae Keun; Kim, Moon-Moo (2010-12-15). "Applications of Chitin and Its Derivatives in Biological Medicine" (in en). International Journal of Molecular Sciences 11 (12): 5152–5164. doi:10.3390/ijms11125152. ISSN 1422-0067. PMID 21614199. 
  18. ↑ De Giglio, E.; Cometa, S.; Ricci, M.A.; Cafagna, D.; Savino, A.M.; Sabbatini, L.; Orciani, M.; Ceci, E. et al. (February 2011). "Ciprofloxacin-modified electrosynthesized hydrogel coatings to prevent titanium-implant-associated infections". Acta Biomaterialia 7 (2): 882–891. doi:10.1016/j.actbio.2010.07.030. ISSN 1742-7061. PMID 20659594. http://dx.doi.org/10.1016/j.actbio.2010.07.030. 
  19. ↑ 19.0 19.1 Chang, Chiung-Hung; Lin, Yu-Hsin; Yeh, Chia-Lin; Chen, Yi-Chi; Chiou, Shu-Fen; Hsu, Yuan-Man; Chen, Yueh-Sheng; Wang, Chi-Chung (2009-11-19). "Nanoparticles Incorporated in pH-Sensitive Hydrogels as Amoxicillin Delivery for Eradication of Helicobacter pylori". Biomacromolecules 11 (1): 133–142. doi:10.1021/bm900985h. ISSN 1525-7797. PMID 19924885. http://dx.doi.org/10.1021/bm900985h. 
  20. ↑ 20.0 20.1 Halpenny, Genevieve M.; Steinhardt, Rachel C.; Okialda, Krystle A.; Mascharak, Pradip K. (2009-06-24). "Characterization of pHEMA-based hydrogels that exhibit light-induced bactericidal effect via release of NO". Journal of Materials Science: Materials in Medicine 20 (11): 2353–2360. doi:10.1007/s10856-009-3795-0. ISSN 0957-4530. PMID 19554428. PMC 2778696. http://dx.doi.org/10.1007/s10856-009-3795-0. 
  21. ↑ Cencer, Morgan; Liu, Yuan; Winter, Audra; Murley, Meridith; Meng, Hao; Lee, Bruce P. (2014-07-17). "Effect of pH on the Rate of Curing and Bioadhesive Properties of Dopamine Functionalized Poly(ethylene glycol) Hydrogels". Biomacromolecules 15 (8): 2861–2869. doi:10.1021/bm500701u. ISSN 1525-7797. PMID 25010812. PMC 4130238. http://dx.doi.org/10.1021/bm500701u. 
  22. ↑ 22.0 22.1 He, Xiaoyan; Liu, Liqin; Han, Huimin; Shi, Wenyu; Yang, Wu; Lu, Xiaoquan (2018-12-18). "Bioinspired and Microgel-Tackified Adhesive Hydrogel with Rapid Self-Healing and High Stretchability". Macromolecules 52 (1): 72–80. doi:10.1021/acs.macromol.8b01678. ISSN 0024-9297. http://dx.doi.org/10.1021/acs.macromol.8b01678. 
  23. ↑ Lei, Hai; Dong, Liang; Li, Ying; Zhang, Junsheng; Chen, Huiyan; Wu, Junhua; Zhang, Yu; Fan, Qiyang et al. (2020-08-12). "Stretchable hydrogels with low hysteresis and anti-fatigue fracture based on polyprotein cross-linkers". Nature Communications 11 (1): 4032. doi:10.1038/s41467-020-17877-z. ISSN 2041-1723. PMID 32788575. PMC 7423981. Bibcode: 2020NatCo..11.4032L. http://dx.doi.org/10.1038/s41467-020-17877-z. 
  24. ↑ 24.0 24.1 Huang, Guoyou; Li, Fei; Zhao, Xin; Ma, Yufei; Li, Yuhui; Lin, Min; Jin, Guorui; Lu, Tian Jian et al. (2017-10-09). "Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment". Chemical Reviews 117 (20): 12764–12850. doi:10.1021/acs.chemrev.7b00094. ISSN 0009-2665. PMID 28991456. PMC 6494624. http://dx.doi.org/10.1021/acs.chemrev.7b00094. 
  25. ↑ 25.0 25.1 25.2 25.3 25.4 Liu, Yi; Hsu, Shan-hui (2018-10-02). "Synthesis and Biomedical Applications of Self-healing Hydrogels". Frontiers in Chemistry 6: 449. doi:10.3389/fchem.2018.00449. ISSN 2296-2646. PMID 30333970. 
  26. ↑ 26.0 26.1 "Hydrogels: Sheets". https://www.woundsource.com/product-category/dressings/hydrogels-sheets. 
  27. ↑ 27.0 27.1 "Hydrogels: Amorphous". https://www.woundsource.com/product-category/dressings/hydrogels-amorphous.. 
  28. ↑ 28.0 28.1 "Hydrogels: Impregnated". https://www.woundsource.com/product-category/dressings/hydrogels-impregnated. 
  29. ↑ 29.0 29.1 He, Jacqueline Jialu; McCarthy, Colleen; Camci-Unal, Gulden (2021-04-09). "Development of Hydrogel‐Based Sprayable Wound Dressings for Second‐ and Third‐Degree Burns". Advanced NanoBiomed Research 1 (6): 2100004. doi:10.1002/anbr.202100004. ISSN 2699-9307. 
  30. ↑ Hendi, Asail; Umair Hassan, Muhammad; Elsherif, Mohamed; Alqattan, Bader; Park, Seongjun; Yetisen, Ali Kemal; Butt, Haider (June 2020). "Healthcare Applications of pH-Sensitive Hydrogel-Based Devices: A Review". International Journal of Nanomedicine 15: 3887–3901. doi:10.2147/ijn.s245743. ISSN 1178-2013. PMID 32581536. 
  31. ↑ Lu, Hao; Yuan, Long; Yu, Xunzhou; Wu, Chengzhou; He, Danfeng; Deng, Jun (2018). "Recent advances of on-demand dissolution of hydrogel dressings". Burns & Trauma 6: 35. doi:10.1186/s41038-018-0138-8. ISSN 2321-3876. PMID 30619904. 
  32. ↑ Witthayaprapakorn, C.; Molloy, Robert; Nalampang, K.; Tighe, B.J. (August 2008). "Design and Preparation of a Bioresponsive Hydrogel for Biomedical Application as a Wound Dressing". Advanced Materials Research 55-57: 681–684. doi:10.4028/www.scientific.net/amr.55-57.681. ISSN 1662-8985. http://dx.doi.org/10.4028/www.scientific.net/amr.55-57.681. 
  33. ↑ Nizioł, Martyna; Paleczny, Justyna; Junka, Adam; Shavandi, Amin; Dawiec-Liśniewska, Anna; Podstawczyk, Daria (2021-06-08). "3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications" (in en). Bioengineering 8 (6): 79. doi:10.3390/bioengineering8060079. ISSN 2306-5354. PMID 34201362. 
  34. ↑ Mi, Luo; Xue, Hong; Li, Yuting; Jiang, Shaoyi (2011-09-07). "A Thermoresponsive Antimicrobial Wound Dressing Hydrogel Based on a Cationic Betaine Ester". Advanced Functional Materials 21 (21): 4028–4034. doi:10.1002/adfm.201100871. ISSN 1616-301X. http://dx.doi.org/10.1002/adfm.201100871. 
  35. ↑ Zoellner, P.; Kapp, H.; Smola, H. (March 2007). "Clinical performance of a hydrogel dressing in chronic wounds: a prospective observational study". Journal of Wound Care 16 (3): 133–136. doi:10.12968/jowc.2007.16.3.27019. ISSN 0969-0700. PMID 17385591. http://dx.doi.org/10.12968/jowc.2007.16.3.27019. 
  36. ↑ Dumville, Jo C; O'Meara, Susan; Deshpande, Sohan; Speak, Katharine (2013-07-12). "Hydrogel dressings for healing diabetic foot ulcers". Cochrane Database of Systematic Reviews 2013 (7): CD009101. doi:10.1002/14651858.cd009101.pub3. ISSN 1465-1858. PMID 23846869. PMC 6486218. http://dx.doi.org/10.1002/14651858.cd009101.pub3. 
  37. ↑ Norman, Gill; Westby, Maggie J; Rithalia, Amber D; Stubbs, Nikki; Soares, Marta O; Dumville, Jo C (2018-06-15). "Dressings and topical agents for treating venous leg ulcers". Cochrane Database of Systematic Reviews 2018 (6): CD012583. doi:10.1002/14651858.cd012583.pub2. ISSN 1465-1858. PMID 29906322. PMC 6513558. http://dx.doi.org/10.1002/14651858.cd012583.pub2. 
  38. ↑ Li, Yuan; Jiang, Shishuang; Song, Liwan; Yao, Zhe; Zhang, Junwen; Wang, Kangning; Jiang, Liping; He, Huacheng et al. (2021-10-08). "Zwitterionic Hydrogel Activates Autophagy to Promote Extracellular Matrix Remodeling for Improved Pressure Ulcer Healing". Frontiers in Bioengineering and Biotechnology 9: 740863. doi:10.3389/fbioe.2021.740863. ISSN 2296-4185. PMID 34692658. 
  39. ↑ Mohd Zohdi, Rozaini; Abu Bakar Zakaria, Zuki; Yusof, Norimah; Mohamed Mustapha, Noordin; Abdullah, Muhammad Nazrul Hakim (2012). "Gelam ( Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing" (in en). Evidence-Based Complementary and Alternative Medicine 2012: 843025. doi:10.1155/2012/843025. ISSN 1741-427X. PMID 21941590. 
  40. ↑ 40.0 40.1 Nuutila, Kristo; Grolman, Josh; Yang, Lu; Broomhead, Michael; Lipsitz, Stuart; Onderdonk, Andrew; Mooney, David; Eriksson, Elof (2020-02-01). "Immediate Treatment of Burn Wounds with High Concentrations of Topical Antibiotics in an Alginate Hydrogel Using a Platform Wound Device" (in en). Advances in Wound Care 9 (2): 48–60. doi:10.1089/wound.2019.1018. ISSN 2162-1918. PMID 31903298. 
  41. ↑ "In third-degree burn treatment, hydrogel helps grow new, scar-free skin". 14 December 2011. http://www.sciencedaily.com/releases/2011/12/111213131956.html. 
  42. ↑ 42.0 42.1 Zhang, Lijun; Yin, Hanxiao; Lei, Xun; Lau, Johnson N. Y.; Yuan, Mingzhou; Wang, Xiaoyan; Zhang, Fangyingnan; Zhou, Fei et al. (2019-11-21). "A Systematic Review and Meta-Analysis of Clinical Effectiveness and Safety of Hydrogel Dressings in the Management of Skin Wounds". Frontiers in Bioengineering and Biotechnology 7: 342. doi:10.3389/fbioe.2019.00342. ISSN 2296-4185. PMID 31824935. 
  43. ↑ Jiang, X; Sun, R; Li, J (2018). "Observation on the effect of hydrogel dressing on radiation-induced skin injury". J. Pract. Clin. Nurs 3: 91–100. 
  44. ↑ Wang, J (2008). "Local treatment of canine bite wound III with silver ion dressing combined with hydrogel: randomized controlled group". Chin. J. Tissue Eng 12: 2659–2662. 
  45. ↑ Chen, L (2015). "Clinical observation of skin wound wet healing treatment.". Huaxi Med 30: 1811–1813. 
  46. ↑ Huang, G (2016). "Treatment and nursing observation of 42 cases of acute skin abrasion and contusion". J. Yangtze Univ. 13: 67–68. 
  47. ↑ Ong, Shin-Yeu; Wu, Jian; Moochhala, Shabbir M.; Tan, Mui-Hong; Lu, Jia (November 2008). "Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties". Biomaterials 29 (32): 4323–4332. doi:10.1016/j.biomaterials.2008.07.034. ISSN 0142-9612. PMID 18708251. http://dx.doi.org/10.1016/j.biomaterials.2008.07.034. 
  48. ↑ Mattioli-Belmonte, M.; Zizzi, A.; Lucarini, G.; Giantomassi, F.; Biagini, G.; Tucci, G.; Orlando, F.; Provinciali, M. et al. (September 2007). "Chitin Nanofibrils Linked to Chitosan Glycolate as Spray, Gel, and Gauze Preparations for Wound Repair". Journal of Bioactive and Compatible Polymers 22 (5): 525–538. doi:10.1177/0883911507082157. ISSN 0883-9115. http://dx.doi.org/10.1177/0883911507082157. 
  49. ↑ 49.0 49.1 Stubbe, Birgit; Mignon, Arn; Declercq, Heidi; Vlierberghe, Sandra; Dubruel, Peter (2019-06-25). "Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment". Macromolecular Bioscience 19 (8): 1900123. doi:10.1002/mabi.201900123. ISSN 1616-5187. PMID 31237746. http://dx.doi.org/10.1002/mabi.201900123. 
  50. ↑ Tavakoli, Shima; Mokhtari, Hamidreza; Kharaziha, Mahshid; Kermanpur, Ahmad; Talebi, Ardeshir; Moshtaghian, Jamal (June 2020). "A multifunctional nanocomposite spray dressing of Kappa-carrageenan-polydopamine modified ZnO/L-glutamic acid for diabetic wounds". Materials Science and Engineering: C 111: 110837. doi:10.1016/j.msec.2020.110837. ISSN 0928-4931. PMID 32279800. http://dx.doi.org/10.1016/j.msec.2020.110837. 
  51. ↑ Ying, Huiyan; Zhou, Juan; Wang, Mingyu; Su, Dandan; Ma, Qiaoqiao; Lv, Guozhong; Chen, Jinghua (August 2019). "In situ formed collagen-hyaluronic acid hydrogel as biomimetic dressing for promoting spontaneous wound healing". Materials Science and Engineering: C 101: 487–498. doi:10.1016/j.msec.2019.03.093. ISSN 0928-4931. PMID 31029343. 
  52. ↑ Kamoun, Elbadawy A.; Kenawy, El-Refaie S.; Chen, Xin (May 2017). "A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings". Journal of Advanced Research 8 (3): 217–233. doi:10.1016/j.jare.2017.01.005. ISSN 2090-1232. PMID 28239493. PMC 5315442. http://dx.doi.org/10.1016/j.jare.2017.01.005. 
  53. ↑ Mir, Mariam; Ali, Murtaza Najabat; Barakullah, Afifa; Gulzar, Ayesha; Arshad, Munam; Fatima, Shizza; Asad, Maliha (2018-02-14). "Synthetic polymeric biomaterials for wound healing: a review". Progress in Biomaterials 7 (1): 1–21. doi:10.1007/s40204-018-0083-4. ISSN 2194-0509. PMID 29446015. PMC 5823812. http://dx.doi.org/10.1007/s40204-018-0083-4. 
  54. ↑ Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E. (2016-09-07). "Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds". Scientific Reports 6 (1): 32670. doi:10.1038/srep32670. ISSN 2045-2322. PMID 27600999. PMC 5013444. Bibcode: 2016NatSR...632670S. http://dx.doi.org/10.1038/srep32670. 
  55. ↑ Cereceres, Stacy; Lan, Ziyang; Bryan, Laura; Whitely, Michael; Wilems, Thomas; Greer, Hunter; Alexander, Ellen Ruth; Taylor, Robert J. et al. (June 2019). "Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate" (in en). APL Bioengineering 3 (2): 026102. doi:10.1063/1.5088801. ISSN 2473-2877. PMID 31123722. 
  56. ↑ Jang, M J; Bae, S K; Jung, Y S; Kim, J C; Kim, J S; Park, S K; Suh, J S; Yi, S J et al. (2021-04-09). "Enhanced wound healing using a 3D printed VEGF-mimicking peptide incorporated hydrogel patch in a pig model". Biomedical Materials 16 (4): 045013. doi:10.1088/1748-605x/abf1a8. ISSN 1748-6041. PMID 33761488. 



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