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Annual Review of Biomedical Engineering

Volume 21, 2019

Hydrogel-Based Strategies to Advance Therapies for Chronic Skin Wounds

Abstract

Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.

Keyword(s): chronic wounds, hydrogel, skin, tissue engineering, wound healing
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/content/journals/10.1146/annurev-bioeng-060418-052422
2019-06-04
2024-04-20
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Literature Cited

  1. 1.
    MedMarket Diligence 2015. Worldwide Wound Management, Forecast to 2026: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World Biddeford, ME: MedMarket Diligence
  2. 2.
    Armstrong DG, Wrobel J, Robbins JM 2007. Guest editorial: Are diabetes-related wounds and amputations worse than cancer?. Int. Wound J. 4:286–87
     [Google Scholar]
  3. 3.
    Eming SA, Martin P, Tomic-Canic M 2014. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med. 6:265sr6
     [Google Scholar]
  4. 4.
    Naghibi M, Smith RP, Baltch AL, Gates SA, Wu DH et al. 1987. The effect of diabetes mellitus on chemotactic and bactericidal activity of human polymorphonuclear leukocytes. Diabetes Res. Clin. Pract. 4:27–35
     [Google Scholar]
  5. 5.
    Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D'Amore PA 2007. Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am. J. Pathol. 170:1178–91
     [Google Scholar]
  6. 6.
    Moore K, Ruge F, Harding KG 1997. T lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers. Br. J. Dermatol. 137:188–94
     [Google Scholar]
  7. 7.
    Zhao G, Usui ML, Lippman SI, James GA, Stewart PS et al. 2013. Biofilms and inflammation in chronic wounds. Adv. Wound Care 2:389–99
     [Google Scholar]
  8. 8.
    Loots MAM, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E 1998. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J. Investig. Dermatol. 111:850–57
     [Google Scholar]
  9. 9.
    Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M 2008. Growth factors and cytokines in wound healing. Wound Repair Regen 16:585–601
     [Google Scholar]
  10. 10.
    Thamm OC, Koenen P, Bader N, Schneider A, Wutzler S et al. 2015. Acute and chronic wound fluids influence keratinocyte function differently. Int. Wound J. 12:143–49
     [Google Scholar]
  11. 11.
    Trengove NJ, Stacey MC, MacAuley S, Bennett N, Gibson J et al. 1999. Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen 7:442–52
     [Google Scholar]
  12. 12.
    Laverdet B, Danigo A, Girard D, Magy L, Demiot C, Desmoulière A 2015. Skin innervation: important roles during normal and pathological cutaneous repair. Histol. Histopathol. 30:875–92
     [Google Scholar]
  13. 13.
    Hong JP, Oh TS. 2012. An algorithm for limb salvage for diabetic foot ulcers. Clin. Plast. Surg. 39:341–52
     [Google Scholar]
  14. 14.
    Moura LIF, Dias AMA, Carvalho E, De Sousa HC 2013. Recent advances on the development of wound dressings for diabetic foot ulcer treatment—a review. Acta Biomater 9:7093–114
     [Google Scholar]
  15. 15.
    Piaggesi A, Låuchli S, Bassetto F, Biedermann T, Marques A et al. 2018. Advanced therapies in wound management: cell and tissue based therapies, physical and bio-physical therapies, smart and IT based technologies. J. Wound Care 27:Suppl. 6A1–137
     [Google Scholar]
  16. 16.
    Mulder G, Tenenhaus M, D'Souza GF 2014. Reduction of diabetic foot ulcer healing times through use of advanced treatment modalities. Int. J. Low. Extrem. Wounds 13:335–46
     [Google Scholar]
  17. 17.
    Armstrong DG, Boulton AJM, Bus SA 2017. Diabetic foot ulcers and their recurrence. N. Engl. J. Med. 376:2367–75
     [Google Scholar]
  18. 18.
    Winter GD. 1962. Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 193:293–94
     [Google Scholar]
  19. 19.
    Williams PA, Phillips GO. 2009. Introduction to food hydrocolloids. Handbook of Hydrocolloids GO Phillips, PA Williams 1–22 Amsterdam: Elsevier. , 2nd ed..
     [Google Scholar]
  20. 20.
    Almdal K, Dyre J, Hvidt S 1993. Towards a phenomenological definition of the term ‘gel. .’ Polym. Gels Netw. 1:5–17
     [Google Scholar]
  21. 21.
    Peppas NA, Hilt JZ, Khademhosseini A, Langer R 2006. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18:1345–60
     [Google Scholar]
  22. 22.
    Thomas S. 2008. Hydrocolloid dressings in the management of acute wounds: a review of the literature. Int. Wound J. 5:602–13
     [Google Scholar]
  23. 23.
    Rice JJ, Martino MM, De Laporte L, Tortelli F, Briquez PS, Hubbell JA 2013. Engineering the regenerative microenvironment with biomaterials. Adv. Healthc. Mater. 2:57–71
     [Google Scholar]
  24. 24.
    Sacco P, Travan A, Borgogna M, Paoletti S, Marsich E 2015. Silver-containing antimicrobial membrane based on chitosan–TPP hydrogel for the treatment of wounds. J. Mater. Sci. Mater. Med. 26:128
     [Google Scholar]
  25. 25.
    He H, Xia DL, Chen YP, Li XD, Chen C et al. 2017. Evaluation of a two-stage antibacterial hydrogel dressing for healing in an infected diabetic wound. J. Biomed. Mater. Res. B 105:1808–17
     [Google Scholar]
  26. 26.
    Brouillard C, Bursztejn A-C, Latarche C, Cuny J-F, Truchetet F et al. 2018. Silver absorption and toxicity evaluation of silver wound dressings in 40 patients with chronic wounds. J. Eur. Acad. Dermatol. Venereol. 32:2295–99
     [Google Scholar]
  27. 27.
    Smith AG, Din A, Denyer M, Crowther NJ, Eagland D et al. 2006. Microengineered surface topography facilitates cell grafting from a prototype hydrogel wound dressing with antibacterial capability. Biotechnol. Prog. 22:1407–15
     [Google Scholar]
  28. 28.
    Du L, Tong L, Jin Y, Jia J, Liu Y et al. 2012. A multifunctional in situ forming hydrogel for wound healing. Wound Repair Regen 20:904–10
     [Google Scholar]
  29. 29.
    Lai PL, Hong DW, Ku KL, Lai ZT, Chu IM 2014. Novel thermosensitive hydrogels based on methoxy polyethylene glycol-co-poly(lactic acid-co-aromatic anhydride) for cefazolin delivery. Nanomed. Nanotechnol. Biol. Med. 10:553–60
     [Google Scholar]
  30. 30.
    Loke WK, Lau SK, Yong LL, Khor E, Sum CK 2000. Wound dressing with sustained anti-microbial capability. J. Biomed. Mater. Res. 53:8–17
     [Google Scholar]
  31. 31.
    Jiang B, Larson JC, Drapala PW, Pérez-Luna VH, Kang-Mieler JJ, Brey EM 2012. Investigation of lysine acrylate containing poly(N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds. J. Biomed. Mater. Res. B 100:668–76
     [Google Scholar]
  32. 32.
    Moritz S, Wiegand C, Wesarg F, Hessler N, Müller FA et al. 2014. Active wound dressings based on bacterial nanocellulose as drug delivery system for octenidine. Int. J. Pharm. 471:45–55
     [Google Scholar]
  33. 33.
    Kumar PTS, Lakshmanan VK, Biswas R, Nair SV, Jayakumar R 2012. Synthesis and biological evaluation of chitin hydrogel/nano ZnO composite bandage as antibacterial wound dressing. J. Biomed. Nanotechnol. 8:891–900
     [Google Scholar]
  34. 34.
    Lee Y, Son JY, Kang JII, Park KM, Park KD 2018. Hydrogen peroxide–releasing hydrogels for enhanced endothelial cell activities and neovascularization. ACS Appl. Mater. Interfaces 10:18372–79
     [Google Scholar]
  35. 35.
    Babavalian H, Latifi AM, Shokrgozar MA, Bonakdar S, Mohammadi S, Moghaddam MM 2015. Analysis of healing effect of alginate sulfate hydrogel dressing containing antimicrobial peptide on wound infection caused by methicillin-resistant Staphylococcus aureus. Jundishapur J. Microbiol 8:e28320
     [Google Scholar]
  36. 36.
    Reimer K, Vogt PM, Broegmann B, Hauser J, Rossbach O et al. 2000. An innovative topical drug formulation for wound healing and infection treatment: in vitro and in vivo investigations of a povidone–iodine liposome hydrogel. Dermatology 201:235–41
     [Google Scholar]
  37. 37.
    Shepherd J, Sarker P, Rimmer S, Swanson L, MacNeil S, Douglas I 2011. Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin. Biomaterials 32:258–67
     [Google Scholar]
  38. 38.
    Zhang X, Soontornworajit B, Zhang Z, Chen N, Wang Y 2012. Enhanced loading and controlled release of antibiotics using nucleic acids as an antibiotic-binding effector in hydrogels. Biomacromolecules 13:2202–10
     [Google Scholar]
  39. 39.
    Roy DC, Tomblyn S, Isaac KM, Kowalczewski CJ, Burmeister DM et al. 2016. Ciprofloxacin-loaded keratin hydrogels reduce infection and support healing in a porcine partial-thickness thermal burn. Wound Repair Regen 24:657–68
     [Google Scholar]
  40. 40.
    Del Gaudio P, De Cicco F, Aquino RP, Picerno P, Russo P et al. 2015. Evaluation of in situ injectable hydrogels as controlled release device for ANXA1 derived peptide in wound healing. Carbohydr. Polym. 115:629–33
     [Google Scholar]
  41. 41.
    Nielsen AL, Madsen F, Larsen KL 2009. Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release. Drug Deliv 16:92–101
     [Google Scholar]
  42. 42.
    Singh D, Singh MR. 2012. Development of antibiotic and debriding enzyme-loaded PLGA microspheres entrapped in PVA–gelatin hydrogel for complete wound management. Artif. Cells Blood Substit. Immobil. Biotechnol. 40:345–53
     [Google Scholar]
  43. 43.
    Li W, Dong K, Ren J, Qu X 2016. A β-lactamase-imprinted responsive hydrogel for the treatment of antibiotic-resistant bacteria. Angew. Chem. Int. Ed. 55:8049–53
     [Google Scholar]
  44. 44.
    Tanihara M, Suzuki Y, Nishimura Y, Suzuki K, Kakimaru Y, Fukunishi Y 1999. A novel microbial infection–responsive drug release system. J. Pharm. Sci. 88:510–14
     [Google Scholar]
  45. 45.
    Zhou G, Ruhan A, Ge H, Wang L, Liu M et al. 2014. Research on a novel poly(vinyl alcohol)/lysine/vanillin wound dressing: biocompatibility, bioactivity and antimicrobial activity. Burns 40:1668–78
     [Google Scholar]
  46. 46.
    Maris P. 1995. Modes of action of disinfectants. Rev. Sci. Technol. 14:47–55
     [Google Scholar]
  47. 47.
    Wong VW, Rustad KC, Galvez MG, Neofytou E, Glotzbach JP et al. 2011. Engineered pullulan–collagen composite dermal hydrogels improve early cutaneous wound healing. Tissue Eng. A 17:631–44
     [Google Scholar]
  48. 48.
    Chen S, Shi J, Zhang M, Chen Y, Wang X et al. 2015. Mesenchymal stem cell–laden anti-inflammatory hydrogel enhances diabetic wound healing. Sci. Rep. 5:18104
     [Google Scholar]
  49. 49.
    Lohmann N, Schirmer L, Atallah P, Wandel E, Ferrer RA et al. 2017. Glycosaminoglycan-based hydrogels capture chemokines and rescue wound healing deficiency. Sci. Transl. Med. 9:eaai9044
     [Google Scholar]
  50. 50.
    Kim YH, Tabata Y. 2016. Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell–derived factor 1 and a macrophage recruitment agent enhances wound closure. J. Biomed. Mater. Res. A 104:942–56
     [Google Scholar]
  51. 51.
    Upadhyay A, Chattopadhyay P, Goyary D, Mitra Mazumder P, Veer V 2014. Ixora coccinea enhances cutaneous wound healing by upregulating the expression of collagen and basic fibroblast growth factor. ISRN Pharmacol 2014:751824
     [Google Scholar]
  52. 52.
    Gong C, Wu Q, Wang Y, Zhang D, Luo F et al. 2013. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials 34:6377–87
     [Google Scholar]
  53. 53.
    Tran NQ, Joung YK, Lih E, Park KD 2011. In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules 12:2872–80
     [Google Scholar]
  54. 54.
    Shukla R, Kashaw SK, Jain AP, Lodhi S 2016. Fabrication of Apigenin loaded gellan gum–chitosan hydrogels (GGCH-HGs) for effective diabetic wound healing. Int. J. Biol. Macromol. 91:1110–19
     [Google Scholar]
  55. 55.
    Zohdi RM, Zakaria ZAB, Yusof N, Mustapha NM, Abdullah MNH 2012. Gelam (Melaleuca spp.) honey-based hydrogel as burn wound dressing. Evid. Complement. Altern. Med. 2012:843025
     [Google Scholar]
  56. 56.
    Li X, Fan R, Tong A, Yang M, Deng J et al. 2015. In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing. Int. J. Pharm. 495:560–71
     [Google Scholar]
  57. 57.
    Reyes-Ortega F, Cifuentes A, Rodríguez G, Aguilar MR, González-Gómez Á et al. 2015. Bioactive bilayered dressing for compromised epidermal tissue regeneration with sequential activity of complementary agents. Acta Biomater 23:103–15
     [Google Scholar]
  58. 58.
    Wieman TJ, Smiell JM, Su Y 1998. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor BB (becaplermin) in patients with chronic neuropathic diabetic ulcers: a phase III randomized placebo-controlled double-blind study. Diabetes Care 21:822–27
     [Google Scholar]
  59. 59.
    Liu Y, Cai S, Shu XZ, Shelby J, Prestwich GD 2007. Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing. Wound Repair Regen 15:245–51
     [Google Scholar]
  60. 60.
    Wu J, Zhu J, He C, Xiao Z, Ye J et al. 2016. Comparative study of heparin–poloxamer hydrogel modified bFGF and aFGF for in vivo wound healing efficiency. ACS Appl. Mater. Interfaces 8:18710–21
     [Google Scholar]
  61. 61.
    Goh MC, Hwang Y, Tae G 2016. Epidermal growth factor loaded heparin-based hydrogel sheet for skin wound healing. Carbohydr. Polym. 147:251–60
     [Google Scholar]
  62. 62.
    Freudenberg U, Zieris A, Chwalek K, Tsurkan MV, Maitz MF et al. 2015. Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds. J. Control. Release 220:79–88
     [Google Scholar]
  63. 63.
    Shute J. 2012. Glycosaminoglycan and chemokine/growth factor interactions. Handb. Exp. Pharmacol. 2012:307–24
     [Google Scholar]
  64. 64.
    Li Q, Niu Y, Diao H, Wang L, Chen X et al. 2017. In situ sequestration of endogenous PDGF-BB with an ECM-mimetic sponge for accelerated wound healing. Biomaterials 148:54–68
     [Google Scholar]
  65. 65.
    Huang S, Zhang Y, Tang L, Deng Z, Lu W et al. 2009. Functional bilayered skin substitute constructed by tissue-engineered extracellular matrix and microsphere-incorporated gelatin hydrogel for wound repair. Tissue Eng. A 15:2617–24
     [Google Scholar]
  66. 66.
    Koria P, Yagi H, Kitagawa Y, Megeed Z, Nahmias Y et al. 2011. Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds. PNAS 108:1034–39
     [Google Scholar]
  67. 67.
    Babavalian H, Tebyanian H, Latifi AM, Shokrgozar MA, Bonakdar S, Shakeri F 2018. The effect of synthetic alginate sulfate hydrogels with recombinant PDGF-BB on wound healing. Bratislava Med. J. 119:391–96
     [Google Scholar]
  68. 68.
    Wise LM, Bodaan CJ, Stuart GS, Real NC, Lateef Z et al. 2018. Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLOS ONE 13:e0197223
     [Google Scholar]
  69. 69.
    Beckert S, Hierlemann H, Müschenborn N, Witte M, Ranke M, Coerper S 2005. Experimental ischemic wounds: correlation of cell proliferation and insulin-like growth factor I expression and its modification by different local IGF-I release systems. Wound Repair Regen 13:278–83
     [Google Scholar]
  70. 70.
    Beckert S, Haack S, Hierlemann H, Farrahi F, Mayer P et al. 2007. Stimulation of steroid-suppressed cutaneous healing by repeated topical application of IGF-I: different mechanisms of action based upon the mode of IGF-I delivery. J. Surg. Res. 139:217–21
     [Google Scholar]
  71. 71.
    Obara K, Ishihara M, Fujita M, Kanatani Y, Hattori H et al. 2005. Acceleration of wound healing in healing-impaired db/db mice with a photocrosslinkable chitosan hydrogel containing fibroblast growth factor 2. Wound Repair Regen 13:390–97
     [Google Scholar]
  72. 72.
    Huang C, Orbay H, Tobita M, Miyamoto M, Tabata Y et al. 2016. Proapoptotic effect of control-released basic fibroblast growth factor on skin wound healing in a diabetic mouse model. Wound Repair Regen 24:65–74
     [Google Scholar]
  73. 73.
    Shamloo A, Sarmadi M, Aghababaie Z, Vossoughi M 2018. Accelerated full-thickness wound healing via sustained bFGF delivery based on a PVA/chitosan/gelatin hydrogel incorporating PCL microspheres. Int. J. Pharm. 537:278–89
     [Google Scholar]
  74. 74.
    Lao G, Yan L, Yang C, Zhang L, Zhang S, Zhou Y 2012. Controlled release of epidermal growth factor from hydrogels accelerates wound healing in diabetic rats. J. Am. Podiatr. Med. Assoc. 102:89–98
     [Google Scholar]
  75. 75.
    Li X, Ye X, Qi J, Fan R, Gao X et al. 2016. EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent. Int. J. Nanomed. 11:3993–4009
     [Google Scholar]
  76. 76.
    Hajimiri M, Shahverdi S, Esfandiari MA, Larijani B, Atyabi F et al. 2015. Preparation of hydrogel embedded polymer–growth factor conjugated nanoparticles as a diabetic wound dressing. Drug Dev. Ind. Pharm. 42:1–13
     [Google Scholar]
  77. 77.
    Tokatlian T, Cam C, Segura T 2015. Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model. Adv. Healthc. Mater. 4:1084–91
     [Google Scholar]
  78. 78.
    Yoon DS, Lee Y, Ryu HA, Jang Y, Lee K-MM et al. 2016. Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing. Acta Biomater 38:59–68
     [Google Scholar]
  79. 79.
    Amadeu TP, Seabra AB, de Oliveira MG, Monte-Alto-Costa A 2008. Nitric oxide donor improves healing if applied on inflammatory and proliferative phase. J. Surg. Res. 149:84–93
     [Google Scholar]
  80. 80.
    Amadeu TP, Seabra AB, de Oliveira MG, Costa AMA 2007. S-Nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair. J. Eur. Acad. Dermatol. Venereol. 21:629–37
     [Google Scholar]
  81. 81.
    Schanuel FS, Raggio Santos KS, Monte-Alto-Costa A, de Oliveira MG 2015. Combined nitric oxide-releasing poly(vinyl alcohol) film/F127 hydrogel for accelerating wound healing. Colloids Surf. B 130:182–91
     [Google Scholar]
  82. 82.
    Champeau M, Póvoa V, Militão L, Cabrini FM, Picheth GF et al. 2018. Supramolecular poly(acrylic acid)/F127 hydrogel with hydration-controlled nitric oxide release for enhancing wound healing. Acta Biomater 74:312–25
     [Google Scholar]
  83. 83.
    Bohl Masters KS, Leibovich SJ, Belem P, West JL, Poole-Warren LA 2002. Effects of nitric oxide releasing poly(vinyl alcohol) hydrogel dressings on dermal wound healing in diabetic mice. Wound Repair Regen 10:286–94
     [Google Scholar]
  84. 84.
    Zhang L, Ma Y, Pan X, Chen S, Zhuang H, Wang S 2018. A composite hydrogel of chitosan/heparin/poly(γ-glutamic acid) loaded with superoxide dismutase for wound healing. Carbohydr. Polym. 180:168–74
     [Google Scholar]
  85. 85.
    Chen H, Jia P, Kang H, Zhang H, Liu Y et al. 2016. Upregulating Hif-1α by hydrogel nanofibrous scaffolds for rapidly recruiting angiogenesis relative cells in diabetic wound. Adv. Healthc. Mater. 5:907–18
     [Google Scholar]
  86. 86.
    Xiao J, Chen S, Yi J, Zhang HF, Ameer GA 2017. A cooperative copper metal–organic framework–hydrogel system improves wound healing in diabetes. Adv. Funct. Mater. 27:1–21
     [Google Scholar]
  87. 87.
    Demirci S, Doğan A, Aydın S, Dülger EÇ, Şahin F 2016. Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation. Mol. Cell. Biochem. 417:119–33
     [Google Scholar]
  88. 88.
    Qiu M, Chen D, Shen C, Shen J, Zhao H, He Y 2016. Platelet-rich plasma-loaded poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) hydrogel dressing promotes full-thickness skin wound healing in a rodent model. Int. J. Mol. Sci. 17:1001
     [Google Scholar]
  89. 89.
    Notodihardjo PV, Morimoto N, Kakudo N, Matsui M, Sakamoto M et al. 2015. Gelatin hydrogel impregnated with platelet-rich plasma releasate promotes angiogenesis and wound healing in murine model. J. Artif. Organs 18:64–71
     [Google Scholar]
  90. 90.
    Houdek MT, Wyles CC, Stalboerger PG, Terzic A, Behfar A, Moran SL 2016. Collagen and fractionated platelet-rich plasma scaffold for dermal regeneration. Plast. Reconstr. Surg. 137:1498–506
     [Google Scholar]
  91. 91.
    Park YG, Lee IH, Park ES, Kim JY 2017. Hydrogel and platelet-rich plasma combined treatment to accelerate wound healing in a nude mouse model. Arch. Plast. Surg. 44:194–201
     [Google Scholar]
  92. 92.
    Henderson PW, Singh SP, Krijgh DD, Yamamoto M, Rafii DC et al. 2011. Stromal-derived factor 1 delivered via hydrogel drug-delivery vehicle accelerates wound healing in vivo. Wound Repair Regen 19:420–25
     [Google Scholar]
  93. 93.
    Rabbany SY, Pastore J, Yamamoto M, Miller T, Rafii S et al. 2010. Continuous delivery of stromal cell–derived factor 1 from alginate scaffolds accelerates wound healing. Cell Transplant 19:399–408
     [Google Scholar]
  94. 94.
    Kim YH, Tabata Y. 2017. Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels. J. Tissue Eng. Regen. Med. 11:2999–3013
     [Google Scholar]
  95. 95.
    Zhu Y, Hoshi R, Chen S, Yi J, Duan C et al. 2016. Sustained release of stromal cell derived factor 1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes. J. Control. Release 238:114–22
     [Google Scholar]
  96. 96.
    Santema TB, Poyck PP, Ubbink DT 2016. Skin grafting and tissue replacement for treating foot ulcers in people with diabetes. Cochrane Database Syst. Rev. 2:CD011255
     [Google Scholar]
  97. 97.
    Rnjak J, Li Z, Maitz PKM, Wise SG, Weiss AS 2009. Primary human dermal fibroblast interactions with open weave three-dimensional scaffolds prepared from synthetic human elastin. Biomaterials 30:6469–77
     [Google Scholar]
  98. 98.
    Annabi N, Mithieux SM, Weiss AS, Dehghani F 2010. Cross-linked open-pore elastic hydrogels based on tropoelastin, elastin and high pressure CO2. Biomaterials 31:1655–65
     [Google Scholar]
  99. 99.
    Park KM, Lee Y, Son JY, Oh DH, Lee JS, Park KD 2012. Synthesis and characterizations of in situ cross-linkable gelatin and 4-arm-PPO-PEO hybrid hydrogels via enzymatic reaction for tissue regenerative medicine. Biomacromolecules 13:604–11
     [Google Scholar]
  100. 100.
    Zhao X, Lang Q, Yildirimer L, Lin ZY, Cui W et al. 2016. Photocrosslinkable gelatin hydrogel for epidermal tissue engineering. Adv. Healthc. Mater. 5:108–18
     [Google Scholar]
  101. 101.
    Ananta M, Brown RA, Mudera V 2012. A rapid fabricated living dermal equivalent for skin tissue engineering: an in vivo evaluation in an acute wound model. Tissue Eng. A 18:353–61
     [Google Scholar]
  102. 102.
    Nicholas MN, Jeschke MG, Amini-Nik S 2016. Cellularized bilayer pullulan–gelatin hydrogel for skin regeneration. Tissue Eng. A 22:754–64
     [Google Scholar]
  103. 103.
    da Silva LP, Santos TC, Rodrigues DB, Pirraco RP, Cerqueira MT et al. 2017. Stem cell–laden hyaluronic acid–based spongy-like hydrogels for an integrated healing of diabetic wounds pathophysiologies. J. Investig. Dermatol. 137:1541–51
     [Google Scholar]
  104. 104.
    Greiser U, Dong Y, Wang F, Tai H, Liu W 2018. A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing. Acta Biomater 75:63–74
     [Google Scholar]
  105. 105.
    Dong Y, Rodrigues M, Kwon SH, Li X, Sigen A et al. 2018. Acceleration of diabetic wound regeneration using an in situ-formed stem-cell-based skin substitute. Adv. Healthc. Mater. 7:1800432
     [Google Scholar]
  106. 106.
    Hsu L-C, Peng B-Y, Chen M-S, Thalib B, Ruslin M et al. 2019. The potential of the stem cells composite hydrogel wound dressings for promoting wound healing and skin regeneration: in vitro and in vivo evaluation. J. Biomed. Mater. Res. B 107:278–85
    [Google Scholar]
  107. 107.
    Shou K, Huang Y, Qi B, Hu X, Ma Z et al. 2018. Induction of mesenchymal stem cell differentiation in the absence of soluble inducer for cutaneous wound regeneration by a chitin nanofiber-based hydrogel. J. Tissue Eng. Regen. Med. 12:e867–80
     [Google Scholar]
  108. 108.
    Xu K, Cantu DA, Fu Y, Kim J, Zheng X et al. 2013. Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds. Acta Biomater 9:8802–14
     [Google Scholar]
  109. 109.
    Kim EJ, Choi JS, Kim JS, Choi YC, Cho YW 2016. Injectable and thermosensitive soluble extracellular matrix and methylcellulose hydrogels for stem cell delivery in skin wounds. Biomacromolecules 17:4–11
     [Google Scholar]
  110. 110.
    Natesan S, Zamora DO, Wrice NL, Baer DG, Christy RJ 2013. Bilayer hydrogel with autologous stem cells derived from debrided human burn skin for improved skin regeneration. J. Burn Care Res. 34:18–30
     [Google Scholar]
  111. 111.
    Kosaraju R, Rennert RC, Maan ZN, Duscher D 2016. Adipose-derived stem cell–seeded hydrogels increase endogenous progenitor cell recruitment and neovascularization in wounds 1. Tissue Eng. A 22:295–305
     [Google Scholar]
  112. 112.
    Garg RK, Rennert RC, Duscher D, Sorkin M, Kosaraju R et al. 2014. Capillary force seeding of hydrogels for adipose-derived stem cell delivery in wounds. Stem Cells Transl. Med. 3:1079–89
     [Google Scholar]
  113. 113.
    Kaisang L, Siyu W, Lijun F, Daoyan P, Xian CJ, Jie S 2017. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing. J. Surg. Res. 217:63–74
     [Google Scholar]
  114. 114.
    Lei Z, Singh G, Min Z, Shixuan C, Xu K et al. 2018. Bone marrow–derived mesenchymal stem cells laden novel thermo-sensitive hydrogel for the management of severe skin wound healing. Mater. Sci. Eng. C 90:159–67
     [Google Scholar]
  115. 115.
    Cheng NC, Lin WJ, Ling TY, Young TH 2017. Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis. Acta Biomater 51:258–67
     [Google Scholar]
  116. 116.
    da Silva LP, Cerqueira MT, Correlo VM, Reis RL, Marques AP 2016. Engineered hydrogel–based matrices for skin wound healing. Wound Healing Biomaterials, vol. 2: Functional Biomaterials MS Ågren 227–50 Amsterdam: Elsevier
     [Google Scholar]
  117. 117.
    Seliktar D. 2012. Designing cell-compatible hydrogels for biomedical applications. Science 336:1124–28
     [Google Scholar]
  118. 118.
    Zeng Y, Zhu L, Han Q, Liu W, Mao X et al. 2015. Preformed gelatin microcryogels as injectable cell carriers for enhanced skin wound healing. Acta Biomater 25:291–303
     [Google Scholar]
  119. 119.
    Rustad KC, Wong VW, Sorkin M, Glotzbach JP, Major MR et al. 2012. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials 33:80–90
     [Google Scholar]
  120. 120.
    Chamberlain G, Fox J, Ashton B, Middleton J 2007. Concise review: Mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–49
     [Google Scholar]
  121. 121.
    Choi SK, Park JK, Kim JH, Lee KM, Kim E et al. 2016. Integrin-binding elastin-like polypeptide as an in situ gelling delivery matrix enhances the therapeutic efficacy of adipose stem cells in healing full-thickness cutaneous wounds. J. Control. Release 237:89–100
     [Google Scholar]
  122. 122.
    Skardal A, Murphy SV, Crowell K, Mack D, Atala A, Soker S 2016. A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery. J. Biomed. Mater. Res. B 105:1986–2000
     [Google Scholar]
  123. 123.
    Klar AS, Güven S, Zimoch J, Zapiórkowska NA, Biedermann T et al. 2016. Characterization of vasculogenic potential of human adipose–derived endothelial cells in a three-dimensional vascularized skin substitute. Pediatr. Surg. Int. 32:17–27
     [Google Scholar]
  124. 124.
    Biedermann T, Klar AS, Böttcher-Haberzeth S, Schiestl C, Reichmann E, Meuli M 2014. Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10 weeks after transplantation. Pediatr. Surg. Int. 30:165–72
     [Google Scholar]
  125. 125.
    Brett E, Zielins ER, Chin M, Januszyk M, Blackshear CP et al. 2017. Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing. Wound Repair Regen 25:414–22
     [Google Scholar]
  126. 126.
    Cerqueira MT, Da Silva LP, Santos TC, Pirraco RP, Correlo VM et al. 2014. Gellan gum–hyaluronic acid spongy-like hydrogels and cells from adipose tissue synergize promoting neoskin vascularization. ACS Appl. Mater. Interfaces 6:19668–79
     [Google Scholar]
  127. 127.
    Davis GE, Senger DR. 2005. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ. Res. 97:1093–107
     [Google Scholar]
  128. 128.
    Ibrahim S, Ramamurthi A. 2008. Hyaluronic acid cues for functional endothelialization of vascular constructs. J. Tissue Eng. Regen. Med. 2:22–32
     [Google Scholar]
  129. 129.
    Shen Y-I, Cho H, Papa AE, Burke JA, Chan XY et al. 2016. Engineered human vascularized constructs accelerate diabetic wound healing. Biomaterials 102:107–19
     [Google Scholar]
  130. 130.
    Sun X, Altalhi W, Nunes SS 2016. Vascularization strategies of engineered tissues and their application in cardiac regeneration. Adv. Drug Deliv. Rev. 96:183–94
     [Google Scholar]
  131. 131.
    Ali S, Saik JE, Gould DJ, Dickinson ME, West JL 2013. Immobilization of cell-adhesive laminin peptides in degradable PEGDA hydrogels influences endothelial cell tubulogenesis. Biores. Open Access 2:241–49
     [Google Scholar]
  132. 132.
    Chwalek K, Tsurkan M V, Freudenberg U, Werner C 2015. Glycosaminoglycan-based hydrogels to modulate heterocellular communication in in vitro angiogenesis models. Sci. Rep. 4:4414
     [Google Scholar]
  133. 133.
    Moon JJ, Saik JE, Poché RA, Leslie-Barbick JE, Lee SH et al. 2010. Biomimetic hydrogels with pro-angiogenic properties. Biomaterials 31:3840–47
     [Google Scholar]
  134. 134.
    Mohandas A, Anisha BS, Chennazhi KP, Jayakumar R 2015. Chitosan–hyaluronic acid/VEGF loaded fibrin nanoparticles composite sponges for enhancing angiogenesis in wounds. Colloids Surf. B 127:105–13
     [Google Scholar]
  135. 135.
    Jessen KR, Mirsky R, Lloyd AC 2015. Schwann cells: development and role in nerve repair. Cold Spring Harb. Perspect. Biol. 7:a020487
     [Google Scholar]
  136. 136.
    Blais M, Grenier M, Berthod F 2009. Improvement of nerve regeneration in tissue-engineered skin enriched with Schwann cells. J. Investig. Dermatol. 129:2895–2900
     [Google Scholar]
  137. 137.
    Hill RP, Gledhill K, Gardner A, Higgins CA, Crawford H et al. 2012. Generation and characterization of multipotent stem cells from established dermal cultures. PLOS ONE 7:e50742
     [Google Scholar]
  138. 138.
    Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K 2013. Glial differentiation of human adipose-derived stem cells: implications for cell-based transplantation therapy. Neuroscience 236:55–65
     [Google Scholar]
  139. 139.
    da Silva LP, Santos TC, Rodrigues DB, Pirraco RP, Cerqueira MT et al. 2017. Stem cell–containing hyaluronic acid–based spongy hydrogels for integrated diabetic wound healing. J. Investig. Dermatol. 137:1541–51
     [Google Scholar]
  140. 140.
    Kant V, Kumar D, Kumar D, Prasad R, Gopal A et al. 2015. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats. Cytokine 73:144–55
     [Google Scholar]
  141. 141.
    Moura LIF, Dias AMA, Suesca E, Casadiegos S, Leal EC et al. 2014. Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice. Biochim. Biophys. Acta 1842:32–43
     [Google Scholar]
/content/journals/10.1146/annurev-bioeng-060418-052422
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Hydrogel-Based Strategies to Advance Therapies for Chronic Skin Wounds
Annual Review of Biomedical Engineering 21, 145 (2019); https://doi.org/10.1146/annurev-bioeng-060418-052422
/content/journals/10.1146/annurev-bioeng-060418-052422
/content/journals/10.1146/annurev-bioeng-060418-052422
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