Microenvironmental cue-regulated exosomes as therapeutic strategies for improving chronic wound healing
Source abstract
Abstract
Abstract Exosomes, which are nanoscale vesicles secreted by almost all cell types via paracrine pathways, play a crucial role in intercellular communication. For nearly a decade, exosomes have been widely exploited to develop novel biologic therapeutic strategies for recalcitrant clinical problems such as chronic wounds. Due to the excellent biocompatibility and immune stability of exosomes, exosome-based therapy has shown greater potential for chronic wound healing than other biotherapies (e.g., transplantation of stem cells) and holds great promise for the clinical treatment of chronic wounds. Here, recent advances in regulating the features and biological functions of cell-derived exosomes by biochemical and biophysical cues in the cell microenvironment are systematically summarized. Subsequently, microenvironmental cue-regulated exosomes as therapeutic strategies to improve chronic wound healing by regulating the inflammatory response, promoting cell proliferation and migration, facilitating angiogenesis, and regulating extracellular matrix (ECM) remodeling are discussed, and hydrogel-based exosome delivery systems used in the treatment of chronic wounds are highlighted. Finally, ongoing challenges and future opportunities in this rapidly developing field are proposed.
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Research context
OpenAlex topics: Extracellular vesicles in disease · Wound Healing and Treatments · Electrospun Nanofibers in Biomedical Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
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1. Rice, J. B. et al. Burden of diabetic foot ulcers for medicare and private insurers. Diabetes Care 37, 651–658 (2014).10.2337/dc13-2176 ↗
2. Martinengo, L. et al. Prevalence of chronic wounds in the general population: systematic review and meta-analysis of observational studies. Ann. Epidemiol. 29, 8–15 (2019).10.1016/j.annepidem.2018.10.005 ↗
3. Olsson, M. et al. The humanistic and economic burden of chronic wounds: a systematic review. Wound Repair Regen. 27, 114–125 (2019).10.1111/wrr.12683 ↗
4. Frykberg, R. G. & Banks, J. Challenges in the treatment of chronic wounds. Adv. Wound Care. 4, 560–582 (2015).10.1089/wound.2015.0635 ↗
5. Akopian, G. et al. Outcomes of conventional wound treatment in a comprehensive wound center. Am. Surg. 72, 314–317 (2006).10.1177/000313480607200407 ↗
6. Nunan, R., Harding, K. G. & Martin, P. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Dis. Model Mech. 7, 1205–1213 (2014).10.1242/dmm.016782 ↗
7. Chou, P.-R. et al. Supercritical carbon dioxide-decellularized porcine acellular dermal matrix combined with autologous adipose-derived stem cells: its role in accelerated diabetic wound healing. Int. J. Med. Sci. 17, 354–367 (2020).10.7150/ijms.41155 ↗
8. Boeringer, T., Gould, L. J. & Koria, P. Protease-resistant growth factor formulations for the healing of chronic wounds. Adv. Wound Care. 9, 612–622 (2020).10.1089/wound.2019.1043 ↗
9. Oneto, P. & Etulain, J. PRP in wound healing applications. Platelets 32, 189–199 (2020).10.1080/09537104.2020.1849605 ↗
10. Huang, Y.-Z., Gou, M., Da, L.-C., Zhang, W.-Q. & Xie, H.-Q. Mesenchymal stem cells for chronic wound healing: current status of preclinical and clinical studies. Tissue Eng. Part B Rev. 26, 555–570 (2020).10.1089/ten.teb.2019.0351 ↗
11. Shin, L. & Peterson, D. A. Human mesenchymal stem cell grafts enhance normal and impaired wound healing by recruiting existing endogenous tissue stem/progenitor cells. Stem Cells Transl. Med. 2, 33–42 (2013).10.5966/sctm.2012-0041 ↗
12. Volarevic, V. et al. Ethical and safety issues of stem cell-based therapy. Int. J. Med. Sci. 15, 36–45 (2018).10.7150/ijms.21666 ↗
13. Song, Y. et al. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice. Cell Biol. Toxicol. 37, 51–64 (2020).10.1007/s10565-020-09530-8 ↗
14. Liu, W. et al. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 103, 196–212 (2020).10.1016/j.actbio.2019.12.020 ↗
15. Ferreira, Ad. F. & Gomes, D. A. Stem cell extracellular vesicles in skin repair. Bioengineering 6, 4 (2018).10.3390/bioengineering6010004 ↗
16. Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science 367, eaau6977 (2020).10.1126/science.aau6977 ↗
17. El Andaloussi, S., Mäger, I., Breakefield, X. O. & Wood, M. J. A. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12, 347–357 (2013).10.1038/nrd3978 ↗
18. Xu, J., Camfield, R. & Gorski, S. M. The interplay between exosomes and autophagy—partners in crime. J. Cell Sci. 131, jcs215210 (2018).10.1242/jcs.215210 ↗
19. Hood, J. L. & Wickline, S. A. A systematic approach to exosome-based translational nanomedicine. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 4, 458–467 (2012).10.1002/wnan.1174 ↗
20. Colombo, M., Raposo, G. & Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255–289 (2014).10.1146/annurev-cellbio-101512-122326 ↗
21. Schorey, J. S. & Harding, C. V. Extracellular vesicles and infectious diseases: new complexity to an old story. J. Clin. Investig. 126, 1181–1189 (2016).10.1172/JCI81132 ↗
22. Najrana, T. et al. Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells. J. Cell. Physiol. 235, 8210–8223 (2020).10.1002/jcp.29476 ↗
23. Han, Y., Ren, J., Bai, Y., Pei, X. & Han, Y. Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R. Int. J. Biochem. Cell Biol. 109, 59–68 (2019).10.1016/j.biocel.2019.01.017 ↗
24. Zhang, J. et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J. Transl. Med. 13, 49 (2015).10.1186/s12967-015-0417-0 ↗
25. Zhang, J. et al. Exosomes derived from human endothelial progenitor cells accelerate cutaneous wound healing by promoting angiogenesis through Erk1/2 signaling. Int. J. Biol. Sci. 12, 1472–1487 (2016).10.7150/ijbs.15514 ↗
26. Hu, L. et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci. Rep. 6, 32993 (2016).10.1038/srep32993 ↗
27. Tao, S. C. et al. Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl. Med. 6, 736–747 (2017).10.5966/sctm.2016-0275 ↗
28. Shafei, S. et al. Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds: an in vivo study. J. Biomed. Mater. Res. A. 108, 545–556 (2020).10.1002/jbm.a.36835 ↗
29. Wang, C. et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics 9, 65–76 (2019).10.7150/thno.29766 ↗
30. Schorey, J. S. & Bhatnagar, S. Exosome function: from tumor immunology to pathogen biology. Traffic 9, 871–881 (2008).10.1111/j.1600-0854.2008.00734.x ↗
31. Li, X. et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model. Exp. Mol. Med. 50, 29 (2018).10.1038/s12276-018-0058-5 ↗
32. Wang, X. et al. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J. Mol. Cell Cardiol. 74, 139–150 (2014).10.1016/j.yjmcc.2014.05.001 ↗
33. Haraszti, R. A. et al. Serum deprivation of mesenchymal stem cells improves exosome activity and alters lipid and protein composition. iScience 16, 230–241 (2019).10.1016/j.isci.2019.05.029 ↗
34. Gray, W. D. et al. Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ. Res. 116, 255–263 (2015).10.1161/CIRCRESAHA.116.304360 ↗
35. Eldh, M. et al. Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PLoS One 5, e15353 (2010).10.1371/journal.pone.0015353 ↗
36. Dougherty, J. A. et al. Human cardiac progenitor cells enhance exosome release and promote angiogenesis under physoxia. Front. Cell Dev. Biol. 8, 130 (2020).10.3389/fcell.2020.00130 ↗
37. Gonzalez-King, H. et al. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells 35, 1747–1759 (2017).10.1002/stem.2618 ↗
38. Du, W. et al. Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer. Biomaterials 133, 70–81 (2017).10.1016/j.biomaterials.2017.04.030 ↗
39. Busbee, P. B., Nagarkatti, M. & Nagarkatti, P. S. Natural indoles, indole-3-carbinol (I3C) and 3,3’-diindolylmethane (DIM), attenuate staphylococcal enterotoxin B-mediated liver injury by downregulating miR-31 expression and promoting caspase-2-mediated apoptosis. PLoS ONE 10, e0118506 (2015).10.1371/journal.pone.0118506 ↗
40. Elliott, D. M., Nagarkatti, M. & Nagarkatti, P. S. 3,39-Diindolylmethane ameliorates staphylococcal enterotoxin B–induced acute lung injury through alterations in the expression of microRNA that target apoptosis and cell-cycle arrest in activated T cells. J. Pharmacol. Exp. Ther. 357, 177–187 (2016).10.1124/jpet.115.226563 ↗
41. Shi, H. et al. 3,3’-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing. Theranostics 7, 1674–1688 (2017).10.7150/thno.18082 ↗
42. Thompson, C. A., Purushothaman, A., Ramani, V. C., Vlodavsky, I. & Sanderson, R. D. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J. Biol. Chem. 288, 10093–10099 (2013).10.1074/jbc.C112.444562 ↗
43. Zuo, L. L. et al. Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma. Oncogenesis 6, 402 (2017).10.1038/s41389-017-0005-7 ↗
44. Zuo, L. et al. Targeting exosomal EBV-LMP1 transfer and miR-203 expression via the NF-κB pathway: the therapeutic role of aspirin in NPC. Mol. Ther. Nucleic Acids 17, 175–184 (2019).10.1016/j.omtn.2019.05.023 ↗
45. Kulshreshtha, A. et al. Simvastatin mediates inhibition of exosome synthesis, localization and secretion via multicomponent interventions. Sci. Rep. 9, 16373 (2019).10.1038/s41598-019-52765-7 ↗
46. Lopatina, T. et al. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun. Signal. 12, 26 (2014).10.1186/1478-811X-12-26 ↗
47. Wang, R., Xu, B. & Xu, H. TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b. Cell Cycle 17, 2756–2765 (2018).10.1080/15384101.2018.1556063 ↗
48. Kao, J.-K. et al. Heat-shock pretreatment reduces expression and release of TSLP from keratinocytes under Th2 environment. Pediatr. Allergy Immunol. 27, 62–69 (2016).10.1111/pai.12482 ↗
49. Jelonek, K., Widlak, P. & Pietrowska, M. The influence of ionizing radiation on exosome composition, secretion and intercellular communication. Protein Pept. Lett. 23, 656–663 (2016).10.2174/0929866523666160427105138 ↗
50. Villasante, A. et al. Recapitulating the size and cargo of tumor exosomes in a tissue-engineered model. Theranostics 6, 1119–1130 (2016).10.7150/thno.13944 ↗
51. Haraszti, R. A. et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol. Ther. 26, 2838–2847 (2018).10.1016/j.ymthe.2018.09.015 ↗
52. Kim, M., Yun, H.-W., Park, D. Y., Choi, B. H. & Min, B.-H. Three-dimensional spheroid culture increases exosome secretion from mesenchymal stem cells. Tissue Eng. Regen. Med. 15, 427–436 (2018).10.1007/s13770-018-0139-5 ↗
53. Gollmann-Tepeköylü, C. et al. miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy. Cardiovasc. Res. 116, 1226–1236 (2020).10.1093/cvr/cvz209 ↗
54. Pironti, G. et al. Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circulation 131, 2120–2130 (2015).10.1161/CIRCULATIONAHA.115.015687 ↗
55. Jeon, H. et al. Extracellular vesicles from KSHV-infected endothelial cells activate the complement system. Oncotarget 8, 99841–99860 (2017).10.18632/oncotarget.21668 ↗
56. Park, S. J., Jeon, H., Yoo, S.-M. & Lee, M.-S. The effect of storage temperature on the biological activity of extracellular vesicles for the complement system. Vitr. Cell. Dev. Biol. Anim. 54, 423–429 (2018).10.1007/s11626-018-0261-7 ↗
57. Li, X., Li, X., Lin, J., Sun, X. & Ding, Q. Exosomes derived from low-intensity pulsed ultrasound-treated dendritic cells suppress tumor necrosis factor-induced endothelial inflammation. J. Ultrasound Med. 38, 2081–2091 (2019).10.1002/jum.14898 ↗
58. Arscott, W. T. et al. Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration. Transl. Oncol. 6, 638–648 (2013).10.1593/tlo.13640 ↗
59. Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007).10.1038/ncb1596 ↗
60. Bruno, S. et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J. Am. Soc. Nephrol. 20, 1053–1067 (2009).10.1681/ASN.2008070798 ↗
61. Gatti, S. et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transpl. 26, 1474–1483 (2011).10.1093/ndt/gfr015 ↗
62. Lai, R. C. et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 4, 214–222 (2010).10.1016/j.scr.2009.12.003 ↗
63. Ranghino, A. et al. Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia. Int. J. Immunopathol. Pharmacol. 25, 75–85 (2012).10.1177/039463201202500110 ↗
64. Zhao, R., Liang, H., Clarke, E., Jackson, C. & Xue, M. Inflammation in chronic wounds. Int. J. Mol. Sci. 17, 2085 (2016).10.3390/ijms17122085 ↗
65. Li, M. et al. Macrophage-derived exosomes accelerate wound healing through their anti-inflammation effects in a diabetic rat model. Artif. Cells Nanomed. Biotechnol. 47, 3793–3803 (2019).10.1080/21691401.2019.1669617 ↗
66. Kim, H. et al. Exosome-guided phenotypic switch of M1 to M2 macrophages for cutaneous wound healing. Adv. Sci. 6, 1900513 (2019).10.1002/advs.201900513 ↗
67. Ti, D. et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J. Transl. Med. 13, 308 (2015).10.1186/s12967-015-0642-6 ↗
68. Li, X. et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation. EBioMedicine 8, 72–82 (2016).10.1016/j.ebiom.2016.04.030 ↗
69. Singer, A. J. & Clark, R. A. Cutaneous wound healing. N. Engl. J. Med. 341, 738–746 (1999).10.1056/NEJM199909023411006 ↗
70. Yang, C. et al. Highly-expressed micoRNA-21 in adipose derived stem cell exosomes can enhance the migration and proliferation of the HaCaT cells by increasing the MMP-9 expression through the PI3K/AKT pathway. Arch. Biochem. Biophys. 681, 108259 (2020).10.1016/j.abb.2020.108259 ↗
71. Shabbir, A., Cox, A., Rodriguez-Menocal, L., Salgado, M. & Van Badiavas, E. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev. 24, 1635–1647 (2015).10.1089/scd.2014.0316 ↗
72. Zhang, B. et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem Cells 33, 2158–2168 (2015).10.1002/stem.1771 ↗
73. Zhang, B. et al. HucMSC exosome-delivered 14-3-3ζ orchestrates self-control of the Wnt response via modulation of YAP during cutaneous regeneration. Stem Cells 34, 2485–2500 (2016).10.1002/stem.2432 ↗
74. Guo, S. C. et al. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics 7, 81–96 (2017).10.7150/thno.16803 ↗
75. Kota, S. K. et al. Aberrant angiogenesis: the gateway to diabetic complications. Indian J. Endocr. Metab. 16, 918–930 (2012).10.4103/2230-8210.102992 ↗
76. Chen, C. Y. et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 8, 1607–1623 (2018).10.7150/thno.22958 ↗
77. Liang, X., Zhang, L., Wang, S., Han, Q. & Zhao, R. C. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J. Cell Sci. 129, 2182–2189 (2016).10.1242/jcs.170373 ↗
78. Gong, M. et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget 8, 45200–45212 (2017).10.18632/oncotarget.16778 ↗
79. Anderson, J. D. et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cells 34, 601–613 (2016).10.1002/stem.2298 ↗
80. Xue, M. & Jackson, C. J. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. Adv. Wound Care. 4, 119–136 (2015).10.1089/wound.2013.0485 ↗
81. Kim, Y.-J. et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem. Biophys. Res. Commun. 493, 1102–1108 (2017).10.1016/j.bbrc.2017.09.056 ↗
82. Jong, O. G., Balkom, B. W. M., Gremmels, H. & Verhaar, M. C. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up‐regulation of lysyl oxidase‐like 2. J. Cell. Mol. Med. 20, 342–350 (2016).10.1111/jcmm.12730 ↗
83. Wang, L. et al. Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. Sci. Rep. 7, 13321 (2017).10.1038/s41598-017-12919-x ↗
84. Fang, S. et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-β/SMAD2 pathway during wound healing. Stem Cells Transl. Med. 5, 1425–1439 (2016).10.5966/sctm.2015-0367 ↗
85. Takahashi, Y. et al. Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J. Biotechnol. 165, 77–84 (2013).10.1016/j.jbiotec.2013.03.013 ↗
86. Smyth, T. et al. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J. Control. Release 199, 145–155 (2015).10.1016/j.jconrel.2014.12.013 ↗
87. Wiklander, O. P. B. et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J. Extracell. Vesicles. 4, 26316 (2015).10.3402/jev.v4.26316 ↗
88. Annabi, N. et al. 25th anniversary article: rational design and applications of hydrogels in regenerative medicine. Adv. Mater. 26, 85–123 (2014).10.1002/adma.201303233 ↗
89. Chen, X. et al. Magnetic and self-healing chitosan-alginate hydrogel encapsulated gelatin microspheres via covalent cross-linking for drug delivery. Mat. Sci. Eng. C.-Mater. 101, 619–629 (2019).10.1016/j.msec.2019.04.012 ↗
90. Mahanta, A. K. et al. Nanoparticle-induced controlled drug delivery using chitosan-based hydrogel and scaffold: application to bone regeneration. Mol. Pharm. 16, 327–338 (2019).10.1021/acs.molpharmaceut.8b00995 ↗
91. Wei, W. et al. Synthesis and characterization of a multi-sensitive polysaccharide hydrogel for drug delivery. Carbohyd. Polym. 177, 275–283 (2017).10.1016/j.carbpol.2017.08.133 ↗
92. Neuerburg, C. et al. Growth factor-mediated augmentation of long bones: evaluation of a BMP-7 loaded thermoresponsive hydrogel in a murine femoral intramedullary injection model. J. Orthop. Surg. Res. 14, 297 (2019).10.1186/s13018-019-1315-6 ↗
93. Chan, S. J. et al. Promoting neuro-supportive properties of astrocytes with epidermal growth factor hydrogels. Stem Cells Transl. Med. 8, 1242–1248 (2019).10.1002/sctm.19-0159 ↗
94. Zhang, X. et al. Stimulation of wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF). Int. J. Nanomed. 13, 3897–3906 (2018).10.2147/IJN.S168998 ↗
95. Ding, L. et al. A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer. J. Mater. Chem. B. 8, 3527–3533 (2020).10.1039/C9TB01610D ↗
96. Chen, Z. et al. Targeted delivery of CRISPR/Cas9-mediated cancer gene therapy via liposome-templated hydrogel nanoparticles. Adv. Funct. Mater. 27, 1703036 (2017).10.1002/adfm.201703036 ↗
97. Xu, N. et al. Wound healing effects of a Curcuma zedoaria polysaccharide with platelet-rich plasma exosomes assembled on chitosan/silk hydrogel sponge in a diabetic rat model. Int. J. Biol. Macromol. 117, 102–107 (2018).10.1016/j.ijbiomac.2018.05.066 ↗
98. Wang, C. et al. The fabrication of a highly efficient self-healing hydrogel from natural biopolymers loaded with exosomes for the synergistic promotion of severe wound healing. Biomater. Sci. 8, 313–324 (2019).10.1039/C9BM01207A ↗
99. Zhang, Y. et al. Preparation of exosomes encapsulated nanohydrogel for accelerating wound healing of diabetic rats by promoting angiogenesis. Mat. Sci. Eng. C.-Mater. 120, 111671 (2021).10.1016/j.msec.2020.111671 ↗
100. Shi, Q. et al. GMSC-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front. Physiol. 8, 904 (2017).10.3389/fphys.2017.00904 ↗