Preparation and applications of the polymeric micelle/hydrogel nanocomposites as biomaterials_Journal of Biomedical Engineering

Authors：

ZENG Ni , JIANG Linrui , MIAO Qingshan , ZHI Yunfei , SHAN Shaoyun ,  SU Hongying

Department of Chemical Engineering, Kunming University of Science and Technology, Kunming 650500, P.R.China;

Corresponding author：

Keywords：

polymeric micelle; nanocomposite hydrogels; drug carrier; wound dressing

DOI：

10.7507/1001-5515.202011024

Video：

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Abstract Full text Figures/Tables Video References Cited by

Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the in vivo stability of micelles. Therefore, micelle-hydrogel nanocomposites have been recently considered as promising biomaterials. In this paper, the structure, properties and methods for preparation of the micelle-hydrogel nanocomposite systems are introduced, and their applications in drug delivery, wound treatment and tissue engineering are reviewed, aiming to provide reference for further development and application of the nanocomposites.

Citation： ZENG Ni, JIANG Linrui, MIAO Qingshan, ZHI Yunfei, SHAN Shaoyun, SU Hongying. Preparation and applications of the polymeric micelle/hydrogel nanocomposites as biomaterials. Journal of Biomedical Engineering, 2021, 38(3): 609-620. doi: 10.7507/1001-5515.202011024 Copy

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2.	Lin Yinlei, He Deliu, Hu Huawen, et al. Polydimethylsiloxane (PDMS)-containing hydrogels prepared by micellar copolymerization in aqueous media. Mater Lett, 2020, 263: 127251.
3.	Burdick J A, Murphy W L. Moving from static to dynamic complexity in hydrogel design. Nat Commun, 2012, 3(1): 1-8.
4.	Ahmed E M. Hydrogel: Preparation, characterization, and applications: A review. J Adv Res, 2015, 6(2): 105-121.
5.	Guo C, Bailey T S. Tailoring mechanical response through coronal layer overlap in tethered micelle hydrogel networks. Soft Matter, 2015, 11(37): 7345-7355.
6.	Lv Juan, Wu Gang, Liu Ying, et al. Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery. Sci China Chem, 2019, 62(5): 637-648.
7.	Anirudhan T S, Parvathy J, Nair A S. A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs. Carbohydr Polym, 2016, 136: 1118-1127.
8.	Rafieian S, Mirzadeh H, Mahdavi H, et al. A review on nanocomposite hydrogels and their biomedical applications. Sci ang Compos Mater, 2019, 26(1): 154-174.
9.	Gaharwar A K, Peppas N A, Khademhosseini A. Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng, 2014, 111(3): 441-453.
10.	Schexnailder P, Schmidt G. Nanocomposite polymer hydrogels. Colloid Polym Sci, 2009, 287(1): 1-11.
11.	Zhang Longshuai, Liu Yuancheng, Zhang Kui, et al. Redox-responsive comparison of diselenide micelles with disulfide micelles. Colloid Polym Sci, 2019, 297(2): 225-238.
12.	Basílio N, García-Río L. Photoswitchable vesicles. Curr Opin Colloid In, 2017, 32: 29-38.
13.	Liu Zhuang, Faraj Y, Ju Xiaojie, et al. Nanocomposite smart hydrogels with improved responsiveness and mechanical properties: A mini review. J Polym Sci Part B: Polym Phys, 2018, 56(19): 1306-1313.
14.	Manjappa A S, Kumbhar P S, Patil A B, et al. Polymeric mixed micelles: improving the anticancer efficacy of single-copolymer micelles. Crit Rev Ther Drug Carrier Syst, 2019, 36(1): 1-58.
15.	Sun X, Wang G, Zhang H, et al. The blood clearance kinetics and pathway of polymeric micelles in cancer drug delivery. ACS Nano, 2018, 12(6): 6179-6192.
16.	Sun Q, Zhou Z, Qiu N, et al. Rational design of cancer nanomedicine: nanoproperty integration and synchronization. Adv Mater, 2017, 29(14): 1606628.
17.	Qin Xianyan, Xu Yingying, Zhou Xu, et al. An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis. Acta Pharm Sin B, 2021, 11(3): 835-847.
18.	Laurano R, Boffito M. Thermosensitive micellar hydrogels as vehicles to deliver drugs with different wettability. Front Bioeng Biotechnol, 2020, 8: 708.
19.	Kang M L, Jeong S Y, Im G I. Hyaluronic acid hydrogel functionalized with self-assembled micelles of amphiphilic PEGylated kartogenin for the treatment of osteoarthritis. Tissue Eng Part A, 2017, 23(13-14): 630-639.
20.	Wen Y, Li F, Li C, et al. High mechanical strength chitosan-based hydrogels cross-linked with poly(ethylene glycol)/polycaprolactone micelles for the controlled release of drugs/growth factors. J Mater Chem B, 2017, 5(5): 961-971.
21.	Xiao L, Zhu J, Londono D J, et al. Mechano-responsive hydrogels crosslinked by block copolymer micelles. Soft Matter, 2012, 8(40): 10233-10237.
22.	Xu Xiaoding, Zhang Xianzheng, Yang Jie, et al. Strategy to introduce a pendent micellar structure into poly(N-isopropylacrylamide) hydrogels. Langmuir, 2007, 23(8): 4231-4236.
23.	Wei S, Liu X, Zhou J, et al. Dual-crosslinked nanocomposite hydrogels based on quaternized chitosan and clindamycin-loaded hyperbranched nanoparticles for potential antibacterial applications. Int J Biol Macromol, 2020, 155: 153-162.
24.	Wen N, Lu S, Xu X, et al. A polysaccharide-based micelle-hydrogel synergistic therapy system for diabetes and vascular diabetes complications treatment. Mater Sci Eng C Mater Biol Appl, 2019, 100: 94-103.
25.	Uchida Y, Fukuda K, Murakami Y. The hydrogel containing a novel vesicle-like soft crosslinker, a “trilayered” polymeric micelle, shows characteristic rheological properties. J Polym Sci Part B: Polym Phys, 2013, 51(2): 124-131.
26.	Nascimento L G L, Casanova F, Silva N F N, et al. Use of a crosslinked casein micelle hydrogel as a carrier for jaboticaba (Myrciaria cauliflora) extract. Food Hydrocoll, 2020, 106: 105872.
27.	Huppertz T, De Kruif C G. Structure and stability of nanogel particles prepared by internal cross-linking of casein micelles. Int Dairy J, 2008, 18(5): 556-565.
28.	Jeon I, Cui J, Illeperuma W R, et al. Extremely stretchable and fast self‐healing hydrogels. Adv Mater, 2016, 28(23): 4678-4683.
29.	牛娜, 李志英, 高婷婷, 等. 疏水缔合水凝胶. 化学进展, 2017, 29(7): 757-765.
30.	Bilici C, Okay O. Shape memory hydrogels via micellar copolymerization of acrylic acid and n-octadecyl acrylate in aqueous media. Macromolecules, 2013, 46(8): 3125-3131.
31.	Xu X D, Liu J, Wu Y P, et al. Biocompatible tough hydrogels via micellar copolymerization of NIPAM and stearyl acrylate: synthesis and characterization. Key Eng Mater, 2017, 748: 96-102.
32.	Cui Zhao, Cheng Ru, Liu Jie, et al. Hydrophobic association hydrogels based on N-acryloyl-alanine and stearyl acrylate using gelatin as emulsifier. RSC Adv, 2016, 6(45): 38957-38963.
33.	Yu Xiaofeng, Qin Zezhao, Wu Haiyang, et al. pH-driven preparation of small, non-aggregated micelles for ultra-stretchable and tough hydrogels. Chem Eng J, 2018, 342: 357-363.
34.	Wang Peng, Deng Guohua, Zhou Lanying, et al. Ultrastretchable, self-healable hydrogels based on dynamic covalent bonding and triblock copolymer micellization. ACS Macro Lett, 2017, 6(8): 881-886.
35.	Lin Yinlei, He Deliu, Chen Zhifeng, et al. Double-crosslinked network design for self-healing, highly stretchable and resilient polymer hydrogels. RSC Adv, 2016, 6(15): 12479-12485.
36.	Zhou Hongwei, Jin Xilang, Yan Bo, et al. Mechanically robust, tough, and self-recoverable hydrogels with molecularly engineered fully flexible crosslinking structure. Macromol Mater Eng, 2017, 302(9): 1700085.
37.	Sun Yuanna, Gao Guorong, Du Gaolai, et al. Super tough, ultrastretchable, and thermoresponsive hydrogels with functionalized triblock copolymer micelles as macro-cross-linkers. ACS Macro Lett, 2014, 3(5): 496-500.
38.	Akca O, Yetiskin B, Okay O. Hydrophobically modified nanocomposite hydrogels with self-healing ability. J Appl Polym Sci, 2020, 137(28): 48853.
39.	Qin Z, Yu X, Wu H, et al. Nonswellable and tough supramolecular hydrogel based on strong micelle cross-linkings. Biomacromolecules, 2019, 20(9): 3399-3407.
40.	Xu Zuxiang, Li Jinhui, Gao Guorong, et al. Tough and self-recoverable hydrogels crosslinked by triblock copolymer micelles and Fe³⁺ coordination. J Polym Sci B Polym Phys, 2018, 56(11): 865-876.
41.	Sheu M T, Jhan H J, Su C Y, et al. Codelivery of doxorubicin-containing thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles enhances local cancer therapy. Colloids Surf B, 2016, 143: 260-270.
42.	Cong Z, Shi Y, Wang Y, et al. A novel controlled drug delivery system based on alginate hydrogel/chitosan micelle composites. Int J Biol Macromol, 2018, 107: 855-864.
43.	Li J, Mooney D J. Designing hydrogels for controlled drug delivery. Nat Rev Mater, 2016, 1(12): 1-17.
44.	Wang Y, Chen L, Tan L, et al. PEG-PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy. Biomaterials, 2014, 35(25): 6972-6985.
45.	Jang J H, Jeong S H, Lee Y B. Preparation and in vitro/in vivo characterization of polymeric nanoparticles containing methotrexate to improve lymphatic delivery. Int J Mol Sci, 2019, 20(13): 33312.
46.	Qindeel M, Khan D, Ahmed N, et al. Surfactant-free, self-assembled nanomicelles-based transdermal hydrogel for safe and targeted delivery of methotrexate against rheumatoid arthritis. ACS nano, 2020, 14(4): 4662-4681.
47.	Fu C, Lin X, Wang J, et al. Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs. J Mater Sci Mater Med, 2016, 27(4): 73.
48.	Zhang Z, He Z, Liang R, et al. Fabrication of a micellar supramolecular hydrogel for ocular drug delivery. Biomacromolecules, 2016, 17(3): 798-807.
49.	Placente D, Benedini L A, Baldini M, et al. Multi-drug delivery system based on lipid membrane mimetic coated nano-hydroxyapatite formulations. Int J Pharm, 2018, 548(1): 559-570.
50.	Angelova A, Angelov B. Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair. Neural Regen Res, 2017, 12(6): 886-889.
51.	Ma Dong, Zhang Hongbin, Tu Kai, et al. Novel supramolecular hydrogel/micelle composite for co-delivery of anticancer drug and growth factor. Soft Matter, 2012, 8(13): 3665-3672.
52.	Gao Nannan, Lü Shaoyu, Gao Chunmei, et al. Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs. Chem Eng J, 2016, 287: 20-29.
53.	Patel M, Kaneko T, Matsumura K. Switchable release nano-reservoirs for co-delivery of drugs via a facile micelle-hydrogel composite. J Mater Chem B, 2017, 5(19): 3488-3497.
54.	Gong C, Wang C, Wang Y, et al. Efficient inhibition of colorectal peritoneal carcinomatosis by drug loaded micelles in thermosensitive hydrogel composites. Nanoscale, 2012, 4(10): 3095-3104.
55.	Wei L, Cai C, Lin J, et al. Dual-drug delivery system based on hydrogel/micelle composites. Biomaterials, 2009, 30(13): 2606-2613.
56.	Guan Zhiyu, Yang Lijun, Wang Weiwei, et al. Thermosensitive micellar hydrogel for enhanced anticancer therapy through redox modulation mediated combinational effects. RSC Adv, 2017, 7(55): 34755-34762.
57.	Liu Zhijia, Xu Guangrui, Wang Chaonan, et al. Shear-responsive injectable supramolecular hydrogel releasing doxorubicin loaded micelles with pH-sensitivity for local tumor chemotherapy. Int J Pharm, 2017, 530(1-2): 53-62.
58.	Ambekar R S, Kandasubramanian B. Advancements in nanofibers for wound dressing: A review. Eur Polym J, 2019, 117: 304-336.
59.	Francesko A, Petkova P, Tzanov T. Hydrogel dressings for advanced wound management. Curr Med Chem, 2018, 25(41): 5782-5797.
60.	Dabiri G, Damstetter E, Phillips T. Choosing a wound dressing based on common wound characteristics. Adv Wound Care, 2016, 5(1): 32-41.
61.	Koehler J, Brandl F P, Goepferich A M. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds. Eur Polym J, 2018, 100: 1-11.
62.	Li Z, Zhou F, Li Z, et al. Hydrogel cross-linked with dynamic covalent bonding and micellization for promoting burn wound healing. ACS Appl Mater Interfaces, 2018, 10(30): 25194-25202.
63.	Ganguly R, Kumar S, Kunwar A, et al. Structural and therapeutic properties of curcumin solubilized pluronic F127 micellar solutions and hydrogels. J Mol Liq, 2020, 314: 113591.
64.	Hu Cheng, Zhang Fanjun, Long Linyu, et al. Dual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healing. J Control Release, 2020, 324: 204-217.
65.	Patel M, Nakaji-Hirabayashi T, Matsumura K. Effect of dual-drug-releasing micelle-hydrogel composite on wound healing in vivo in full-thickness excision wound rat model. J Biomed Mater Res A, 2019, 107(5): 1094-1106.
66.	Zhao H, Liu M, Zhang Y, et al. Nanocomposite hydrogels for tissue engineering applications. Nanoscale, 2020, 12(28): 14976-14995.
67.	Cho I S, Ooya T. Cell-encapsulating hydrogel puzzle: Polyrotaxane-based self-healing hydrogels. Chem Eur J, 2020, 26(4): 913-920.
68.	Yan Shifeng, Ren Jie, Jian Yuhang, et al. Injectable maltodextrin-based micelle/hydrogel composites for simvastatin-controlled release. Biomacromolecules, 2018, 19(12): 4554-4564.

1. Caló E, Khutoryanskiy V V. Biomedical applications of hydrogels: A review of patents and commercial products. Eur Polym J, 2015, 65: 252-267.
2. Lin Yinlei, He Deliu, Hu Huawen, et al. Polydimethylsiloxane (PDMS)-containing hydrogels prepared by micellar copolymerization in aqueous media. Mater Lett, 2020, 263: 127251.
3. Burdick J A, Murphy W L. Moving from static to dynamic complexity in hydrogel design. Nat Commun, 2012, 3(1): 1-8.
4. Ahmed E M. Hydrogel: Preparation, characterization, and applications: A review. J Adv Res, 2015, 6(2): 105-121.
5. Guo C, Bailey T S. Tailoring mechanical response through coronal layer overlap in tethered micelle hydrogel networks. Soft Matter, 2015, 11(37): 7345-7355.
6. Lv Juan, Wu Gang, Liu Ying, et al. Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery. Sci China Chem, 2019, 62(5): 637-648.
7. Anirudhan T S, Parvathy J, Nair A S. A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs. Carbohydr Polym, 2016, 136: 1118-1127.
8. Rafieian S, Mirzadeh H, Mahdavi H, et al. A review on nanocomposite hydrogels and their biomedical applications. Sci ang Compos Mater, 2019, 26(1): 154-174.
9. Gaharwar A K, Peppas N A, Khademhosseini A. Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng, 2014, 111(3): 441-453.
10. Schexnailder P, Schmidt G. Nanocomposite polymer hydrogels. Colloid Polym Sci, 2009, 287(1): 1-11.
11. Zhang Longshuai, Liu Yuancheng, Zhang Kui, et al. Redox-responsive comparison of diselenide micelles with disulfide micelles. Colloid Polym Sci, 2019, 297(2): 225-238.
12. Basílio N, García-Río L. Photoswitchable vesicles. Curr Opin Colloid In, 2017, 32: 29-38.
13. Liu Zhuang, Faraj Y, Ju Xiaojie, et al. Nanocomposite smart hydrogels with improved responsiveness and mechanical properties: A mini review. J Polym Sci Part B: Polym Phys, 2018, 56(19): 1306-1313.
14. Manjappa A S, Kumbhar P S, Patil A B, et al. Polymeric mixed micelles: improving the anticancer efficacy of single-copolymer micelles. Crit Rev Ther Drug Carrier Syst, 2019, 36(1): 1-58.
15. Sun X, Wang G, Zhang H, et al. The blood clearance kinetics and pathway of polymeric micelles in cancer drug delivery. ACS Nano, 2018, 12(6): 6179-6192.
16. Sun Q, Zhou Z, Qiu N, et al. Rational design of cancer nanomedicine: nanoproperty integration and synchronization. Adv Mater, 2017, 29(14): 1606628.
17. Qin Xianyan, Xu Yingying, Zhou Xu, et al. An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis. Acta Pharm Sin B, 2021, 11(3): 835-847.
18. Laurano R, Boffito M. Thermosensitive micellar hydrogels as vehicles to deliver drugs with different wettability. Front Bioeng Biotechnol, 2020, 8: 708.
19. Kang M L, Jeong S Y, Im G I. Hyaluronic acid hydrogel functionalized with self-assembled micelles of amphiphilic PEGylated kartogenin for the treatment of osteoarthritis. Tissue Eng Part A, 2017, 23(13-14): 630-639.
20. Wen Y, Li F, Li C, et al. High mechanical strength chitosan-based hydrogels cross-linked with poly(ethylene glycol)/polycaprolactone micelles for the controlled release of drugs/growth factors. J Mater Chem B, 2017, 5(5): 961-971.
21. Xiao L, Zhu J, Londono D J, et al. Mechano-responsive hydrogels crosslinked by block copolymer micelles. Soft Matter, 2012, 8(40): 10233-10237.
22. Xu Xiaoding, Zhang Xianzheng, Yang Jie, et al. Strategy to introduce a pendent micellar structure into poly(N-isopropylacrylamide) hydrogels. Langmuir, 2007, 23(8): 4231-4236.
23. Wei S, Liu X, Zhou J, et al. Dual-crosslinked nanocomposite hydrogels based on quaternized chitosan and clindamycin-loaded hyperbranched nanoparticles for potential antibacterial applications. Int J Biol Macromol, 2020, 155: 153-162.
24. Wen N, Lu S, Xu X, et al. A polysaccharide-based micelle-hydrogel synergistic therapy system for diabetes and vascular diabetes complications treatment. Mater Sci Eng C Mater Biol Appl, 2019, 100: 94-103.
25. Uchida Y, Fukuda K, Murakami Y. The hydrogel containing a novel vesicle-like soft crosslinker, a “trilayered” polymeric micelle, shows characteristic rheological properties. J Polym Sci Part B: Polym Phys, 2013, 51(2): 124-131.
26. Nascimento L G L, Casanova F, Silva N F N, et al. Use of a crosslinked casein micelle hydrogel as a carrier for jaboticaba (Myrciaria cauliflora) extract. Food Hydrocoll, 2020, 106: 105872.
27. Huppertz T, De Kruif C G. Structure and stability of nanogel particles prepared by internal cross-linking of casein micelles. Int Dairy J, 2008, 18(5): 556-565.
28. Jeon I, Cui J, Illeperuma W R, et al. Extremely stretchable and fast self‐healing hydrogels. Adv Mater, 2016, 28(23): 4678-4683.
29. 牛娜, 李志英, 高婷婷, 等. 疏水缔合水凝胶. 化学进展, 2017, 29(7): 757-765.
30. Bilici C, Okay O. Shape memory hydrogels via micellar copolymerization of acrylic acid and n-octadecyl acrylate in aqueous media. Macromolecules, 2013, 46(8): 3125-3131.
31. Xu X D, Liu J, Wu Y P, et al. Biocompatible tough hydrogels via micellar copolymerization of NIPAM and stearyl acrylate: synthesis and characterization. Key Eng Mater, 2017, 748: 96-102.
32. Cui Zhao, Cheng Ru, Liu Jie, et al. Hydrophobic association hydrogels based on N-acryloyl-alanine and stearyl acrylate using gelatin as emulsifier. RSC Adv, 2016, 6(45): 38957-38963.
33. Yu Xiaofeng, Qin Zezhao, Wu Haiyang, et al. pH-driven preparation of small, non-aggregated micelles for ultra-stretchable and tough hydrogels. Chem Eng J, 2018, 342: 357-363.
34. Wang Peng, Deng Guohua, Zhou Lanying, et al. Ultrastretchable, self-healable hydrogels based on dynamic covalent bonding and triblock copolymer micellization. ACS Macro Lett, 2017, 6(8): 881-886.
35. Lin Yinlei, He Deliu, Chen Zhifeng, et al. Double-crosslinked network design for self-healing, highly stretchable and resilient polymer hydrogels. RSC Adv, 2016, 6(15): 12479-12485.
36. Zhou Hongwei, Jin Xilang, Yan Bo, et al. Mechanically robust, tough, and self-recoverable hydrogels with molecularly engineered fully flexible crosslinking structure. Macromol Mater Eng, 2017, 302(9): 1700085.
37. Sun Yuanna, Gao Guorong, Du Gaolai, et al. Super tough, ultrastretchable, and thermoresponsive hydrogels with functionalized triblock copolymer micelles as macro-cross-linkers. ACS Macro Lett, 2014, 3(5): 496-500.
38. Akca O, Yetiskin B, Okay O. Hydrophobically modified nanocomposite hydrogels with self-healing ability. J Appl Polym Sci, 2020, 137(28): 48853.
39. Qin Z, Yu X, Wu H, et al. Nonswellable and tough supramolecular hydrogel based on strong micelle cross-linkings. Biomacromolecules, 2019, 20(9): 3399-3407.
40. Xu Zuxiang, Li Jinhui, Gao Guorong, et al. Tough and self-recoverable hydrogels crosslinked by triblock copolymer micelles and Fe³⁺ coordination. J Polym Sci B Polym Phys, 2018, 56(11): 865-876.
41. Sheu M T, Jhan H J, Su C Y, et al. Codelivery of doxorubicin-containing thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles enhances local cancer therapy. Colloids Surf B, 2016, 143: 260-270.
42. Cong Z, Shi Y, Wang Y, et al. A novel controlled drug delivery system based on alginate hydrogel/chitosan micelle composites. Int J Biol Macromol, 2018, 107: 855-864.
43. Li J, Mooney D J. Designing hydrogels for controlled drug delivery. Nat Rev Mater, 2016, 1(12): 1-17.
44. Wang Y, Chen L, Tan L, et al. PEG-PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy. Biomaterials, 2014, 35(25): 6972-6985.
45. Jang J H, Jeong S H, Lee Y B. Preparation and in vitro/in vivo characterization of polymeric nanoparticles containing methotrexate to improve lymphatic delivery. Int J Mol Sci, 2019, 20(13): 33312.
46. Qindeel M, Khan D, Ahmed N, et al. Surfactant-free, self-assembled nanomicelles-based transdermal hydrogel for safe and targeted delivery of methotrexate against rheumatoid arthritis. ACS nano, 2020, 14(4): 4662-4681.
47. Fu C, Lin X, Wang J, et al. Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs. J Mater Sci Mater Med, 2016, 27(4): 73.
48. Zhang Z, He Z, Liang R, et al. Fabrication of a micellar supramolecular hydrogel for ocular drug delivery. Biomacromolecules, 2016, 17(3): 798-807.
49. Placente D, Benedini L A, Baldini M, et al. Multi-drug delivery system based on lipid membrane mimetic coated nano-hydroxyapatite formulations. Int J Pharm, 2018, 548(1): 559-570.
50. Angelova A, Angelov B. Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair. Neural Regen Res, 2017, 12(6): 886-889.
51. Ma Dong, Zhang Hongbin, Tu Kai, et al. Novel supramolecular hydrogel/micelle composite for co-delivery of anticancer drug and growth factor. Soft Matter, 2012, 8(13): 3665-3672.
52. Gao Nannan, Lü Shaoyu, Gao Chunmei, et al. Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs. Chem Eng J, 2016, 287: 20-29.
53. Patel M, Kaneko T, Matsumura K. Switchable release nano-reservoirs for co-delivery of drugs via a facile micelle-hydrogel composite. J Mater Chem B, 2017, 5(19): 3488-3497.
54. Gong C, Wang C, Wang Y, et al. Efficient inhibition of colorectal peritoneal carcinomatosis by drug loaded micelles in thermosensitive hydrogel composites. Nanoscale, 2012, 4(10): 3095-3104.
55. Wei L, Cai C, Lin J, et al. Dual-drug delivery system based on hydrogel/micelle composites. Biomaterials, 2009, 30(13): 2606-2613.
56. Guan Zhiyu, Yang Lijun, Wang Weiwei, et al. Thermosensitive micellar hydrogel for enhanced anticancer therapy through redox modulation mediated combinational effects. RSC Adv, 2017, 7(55): 34755-34762.
57. Liu Zhijia, Xu Guangrui, Wang Chaonan, et al. Shear-responsive injectable supramolecular hydrogel releasing doxorubicin loaded micelles with pH-sensitivity for local tumor chemotherapy. Int J Pharm, 2017, 530(1-2): 53-62.
58. Ambekar R S, Kandasubramanian B. Advancements in nanofibers for wound dressing: A review. Eur Polym J, 2019, 117: 304-336.
59. Francesko A, Petkova P, Tzanov T. Hydrogel dressings for advanced wound management. Curr Med Chem, 2018, 25(41): 5782-5797.
60. Dabiri G, Damstetter E, Phillips T. Choosing a wound dressing based on common wound characteristics. Adv Wound Care, 2016, 5(1): 32-41.
61. Koehler J, Brandl F P, Goepferich A M. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds. Eur Polym J, 2018, 100: 1-11.
62. Li Z, Zhou F, Li Z, et al. Hydrogel cross-linked with dynamic covalent bonding and micellization for promoting burn wound healing. ACS Appl Mater Interfaces, 2018, 10(30): 25194-25202.
63. Ganguly R, Kumar S, Kunwar A, et al. Structural and therapeutic properties of curcumin solubilized pluronic F127 micellar solutions and hydrogels. J Mol Liq, 2020, 314: 113591.
64. Hu Cheng, Zhang Fanjun, Long Linyu, et al. Dual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healing. J Control Release, 2020, 324: 204-217.
65. Patel M, Nakaji-Hirabayashi T, Matsumura K. Effect of dual-drug-releasing micelle-hydrogel composite on wound healing in vivo in full-thickness excision wound rat model. J Biomed Mater Res A, 2019, 107(5): 1094-1106.
66. Zhao H, Liu M, Zhang Y, et al. Nanocomposite hydrogels for tissue engineering applications. Nanoscale, 2020, 12(28): 14976-14995.
67. Cho I S, Ooya T. Cell-encapsulating hydrogel puzzle: Polyrotaxane-based self-healing hydrogels. Chem Eur J, 2020, 26(4): 913-920.
68. Yan Shifeng, Ren Jie, Jian Yuhang, et al. Injectable maltodextrin-based micelle/hydrogel composites for simvastatin-controlled release. Biomacromolecules, 2018, 19(12): 4554-4564.

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