Sprayable supramolecular hydrogel with minimalism for wilderness first aid: integration of mechanical performance and biofunctionality

Abstract

The ideal wound care materials for wilderness first aid should be convenient for storage, easy to use, adhesive, antibacterial, anti-inflammatory, pro-angiogenic, wound-closure promoting, and simple for clinical translation. To meet all requirements, we developed a supramolecular FPC hydrogel by simply co-assembling 2-amino-2′-fluoro-2′-deoxyadenosine (FA), polydeoxyribonucleotide (PDRN), and collagen III (COL-III)-fully active pharmaceutical ingredients. Based on the abundant hydrogen bonding interactions among FA, PDRN, and COL-III, this hydrogel exhibited sprayability, tissue adhesiveness, and superior biological performance. In vivo studies showed that due to synergistic effects among FA, PDRN, and COL-III, FPC hydrogels offered significant anti-inflammatory benefits and angiogenic capabilities, which promoted granulation tissue formation, collagen deposition, wound tissue epithelialization, and effectively sped up wound healing. Furthermore, the FPC hydrogel could be conveniently stored in a bottle and sterilized through boiling, making it well-suited for wilderness first aid applications. This hydrogel has the potential to transform wound care by offering a versatile solution for both outdoor and everyday wound management needs.

Graphical Abstract

Keywords

Sprayable wound dressing / Supramolecular hydrogel / Wilderness first aid / Anti-inflammatory / Angiogenesis

References

[1] Peña OA, Martin P. Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol, 2024, 25(8): 599-616

[2] Cetin FN, Mignon A, Van Vlierberghe S, Kolouchova K. Polymer- and lipid-based nanostructures serving wound healing applications: a review. Adv Healthcare Mat, 2024, 14: 2402699

[3] Wang S, Wu W-Y, Yeo JCC, Soo XYD, Thitsartarn W, Liu S, Tan BH, Suwardi A, Li Z, Zhu Q, Loh XJ. Responsive hydrogel dressings for intelligent wound management. BMEMat, 2023, 1(2): e12021

[4] Jiao F, Zhao W, Zhao W, Wang Y, Deng Y, Chang S, Sun J, Lou Q, Wang L, Shan C-X, Xiao Y, Dong L. Biomass-derived washable composites for accelerating the healing of infected wounds. BMEMat, 2023, 1(4): e12055

[5] Wang C, Shirzaei Sani E, Shih C-D, Lim CT, Wang J, Armstrong DG, Gao W. Wound management materials and technologies from bench to bedside and beyond. Nat Rev Mater, 2024, 9(8): 550-566

[6] Nezhad-Mokhtari P, Hasany M, Kohestanian M, Dolatshahi-Pirouz A, Milani M, Mehrali M. Recent advancements in bioadhesive self-healing hydrogels for effective chronic wound care. Adv Colloid Interface Sci, 2024, 334 103306

[7] Cheng J, Wang H, Gao J, Liu X, Li M, Wu D, Liu J, Wang X, Wang Z, Tang P. First-aid hydrogel wound dressing with reliable hemostatic and antibacterial capability for traumatic injuries. Adv Healthc Mater, 2023, 12(25): 2300312

[8] Bian S, Ye H, Wang P, Li C, Guo X, Guan M, Feng S. Antibacterial hydrogel: the sniper of chronic wounds. BMEMat, 2025,

[9] Wu L, Yang X, Jia H, Xiao L, Gao C, Hu Z, Wang J, Guo Y, Wang X, Liu T, Cao R, Zhao RC. Freestanding hydrogen-bonded organic framework membrane for efficient wound healing. Adv Mater, 2024, 36(47): 2411229

[10] Nosrati H, Aramideh Khouy R, Nosrati A, Khodaei M, Banitalebi-Dehkordi M, Ashrafi-Dehkordi K, Sanami S, Alizadeh Z. Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis. J Nanobiotechnology, 2021, 19(1): 1

[11] Zhu R, Huang Z, Zhang J, Shi G, Cai X, Dou R, Tang J, Zhang C, Zhao Y, Chen J. The potential of collagen-based materials for wound management. Mater Today Chem, 2024, 41 102295

[12] Li X, Gong JP. Design principles for strong and tough hydrogels. Nat Rev Mater, 2024, 9(6): 380-98

[13] Liang C, Dudko V, Khoruzhenko O, Hong X, Lv Z-P, Tunn I, Umer M, Timonen JVI, Linder MB, Breu J, Ikkala O, Zhang H. Stiff and self-healing hydrogels by polymer entanglements in co-planar nanoconfinement. Nat Mater, 2025, 24(4): 599-606

[14] Yu R, Li M, Li Z, Pan G, Liang Y, Guo B. Supramolecular thermo-contracting adhesive hydrogel with self-removability simultaneously enhancing noninvasive wound closure and MRSA-infected wound healing. Adv Healthc Mater, 2022, 11(13): e2102749

[15] Lim JYC, Lin Q, Xue K, Loh XJ. Recent advances in supramolecular hydrogels for biomedical applications. Mater Today Adv, 2019, 3 100021

[16] Zhuo S, Liang Y, Wu Z, Zhao X, Han Y, Guo B. Supramolecular hydrogels for wound repair and hemostasis. Mater Horiz, 2024, 11(1): 37-101

[17] Tang H, Gao Y, Zhang J, Li Z, Gao Q, Cai P, Chen X, Guo X, van Esch JH, Wang Y, Xuan F-Z. Harnessing the hofmeister effect for dynamic self-assembly of supramolecular hydrogels. Angewandte Chemie Intern Ed, 2025,

[18] Dong R, Pang Y, Su Y, Zhu X. Supramolecular hydrogels: synthesis, properties and their biomedical applications. Biomater Sci, 2015, 3(7): 937-54

[19] He L, Jiang Y, Wei J, Zhang Z, Hong T, Ren Z, Huang J, Huang F, Stang PJ, Li S. Highly robust supramolecular polymer networks crosslinked by a tiny amount of metallacycles. Nat Commun, 2024, 15(1): 3050

[20] Li Y, Zhu C, Dong Y, Liu D. Supramolecular hydrogels: mechanical strengthening with dynamics. Polymer, 2020, 210 122993

[21] Gu Y, Wu W, Zhang C, Li X, Guo X, Wang Y, Yuan Y, Jiang B, Jin Y. Multi-solvent-induced gradient aggregation rendered superstrong, tough, stretchable, and fatigue-resistant lignin-based supramolecular hydrogels. Adv Funct Mater, 2025, 35(11): 2417206

[22] Gu Y, Xu C, Wang Y, Luo J, Shi D, Wu W, Chen L, Jin Y, Jiang B, Chen C. Compressible, anti-fatigue, extreme environment adaptable, and biocompatible supramolecular organohydrogel enabled by lignosulfonate triggered noncovalent network. Nat Commun, 2025, 16(1): 160

[23] Wang Z, Zhang Y, Yin Y, Liu J, Li P, Zhao Y, Bai D, Zhao H, Han X, Chen Q. High-strength and injectable supramolecular hydrogel self-assembled by monomeric nucleoside for tooth-extraction wound healing. Adv Mater, 2022, 34(13): 2108300

[24] Wang Z, Liu J, Zhang Y, Qi J, Han X, Zhao X, Bai D, Zhao H, Chen Q. Intrinsic contributions of 2’-Hydroxyl to the hydration of nucleosides at the monomeric level. Chemistry, 2020, 26(71): 17046-55

[25] Tamate R, Hashimoto K, Horii T, Hirasawa M, Li X, Shibayama M, Watanabe M. Self-healing micellar ion gels based on multiple hydrogen bonding. Adv Mater, 2018, 30(36): 1802792

[26] Guo X, Zhang L, Zhuo H, Chen C, Yang H, Li T, Qi H, Zhai W. Robust zwitterionic hydrogels enabled by consolidated supramolecular networks and spatially hierarchical structures. Nat Commun, 2025, 16(1): 9454

[27] Wu J, Zhang Z, Wu Z, Liu D, Yang X, Wang Y, Jia X, Xu X, Jiang P, Wang X. Strong and ultra-tough supramolecular hydrogel enabled by strain-induced microphase separation. Adv Funct Mater, 2023, 33(3): 2210395

[28] Gokaltun AA, Fan L, Mazzaferro L, Byrne D, Yarmush ML, Dai T, Asatekin A, Usta OB. Supramolecular hybrid hydrogels as rapidly on-demand dissoluble, self-healing, and biocompatible burn dressings. Bioact Mater, 2023, 25: 415-29

[29] Li X, Qu S, Ouyang Q, Qin F, Guo J, Qin M, Zhang J. A multifunctional composite nanoparticle with antibacterial activities, anti-inflammatory, and angiogenesis for diabetic wound healing. Int J Biol Macromol, 2024, 260 129531

[30] Lee HY, Kim D-S, Hwang GY, Lee J-K, Lee H-L, Jung J-W, Hwang SY, Baek S-W, Yoon S, Ha Y, Kim KN, Han I, Han DK, Lee CK. Multi-modulation of immune-inflammatory response using bioactive molecule-integrated PLGA composite for spinal fusion. Mater Today Bio, 2023, 19 100611

[31] Ko KW, Park SY, Lee EH, Yoo YI, Kim DS, Kim JY, Kwon TG, Han DK. Integrated bioactive scaffold with polydeoxyribonucleotide and stem-cell-derived extracellular vesicles for kidney regeneration. ACS Nano, 2021, 15(4): 7575-85

[32] Dong Z, Liu Q, Han X, Zhang X, Wang X, Hu C, Li X, Liang J, Chen Y, Fan Y. Electrospun nanofibrous membranes of recombinant human collagen type III promote cutaneous wound healing. J Mater Chem B, 2023, 11(27): 6346-60

[33] Lu J, Shi X, Fu Q, Li Y, Zhou Z, Lu N, Zhu L. Extracellular vesicles from inflammatory-stimulated BMSCs ameliorate osteoarthritis via Rpl14 mediated synovial macrophage polarization. Chem Eng J, 2024, 499 156541

[34] Li T, Xu L, Wei Z, Zhang S, Liu X, Yang Y, Gu Y, Zhang J. ELF5 drives angiogenesis suppression though stabilizing WDTC1 in renal cell carcinoma. Mol Cancer, 2023, 22(1): 184

[35] Zhang T, Ma H, Zhang X, Shi S, Lin Y. Functionalized DNA nanomaterials targeting toll-like receptor 4 prevent bisphosphonate-related osteonecrosis of the jaw via regulating mitochondrial homeostasis in macrophages. Adv Funct Mater, 2023, 33(15): 2213401

[36] Ge X, Mao M, Yu H, Liu J, Kong J, Sun Y, Huang W, Wang DY, Wang Y. Application of self powered black phosphorus nanosheets-based hydrogel skin patch in wound healing of diabetes. Nano Energy, 2024, 131 110289

[37] Shang S, Zhuang K, Chen J, Zhang M, Jiang S, Li W. A bioactive composite hydrogel dressing that promotes healing of both acute and chronic diabetic skin wounds. Bioact Mater, 2024, 34: 298-310

[38] Liu Y, Wang K, Ren W, Gao N, Li J, Wang H. A dry patch with in situ solid-to-gel transformation for all-in-one skin wound care. ACS Appl Mater Interfaces, 2024, 16(46): 64087-100

[39] Hu A-H, Duan Q-X, Xiong X-Y, Kang Z, Bai A-M, Yin M-M, Hu Y-J. Revealing the effects of ligands of silver nanoclusters on the interactions between them and ctDNA: abstraction to visualization. Int J Biol Macromol, 2023, 236 123965

[40] He H, Wei N, Xie Y, Wang L, Yao L, Xiao J. Self-assembling triple-helix recombinant collagen hydrogel enriched with tyrosine. ACS Biomater Sci Eng, 2024, 10(5): 3268-79

[41] Liu Y, Wang R, Wang D, Sun Z, Liu F, Zhang D, Wang D. Development of a food packaging antibacterial hydrogel based on gelatin, chitosan, and 3-phenyllactic acid for the shelf-life extension of chilled chicken. Food Hydrocoll, 2022, 127 107546

[42] Tang N, Zhang R, Zheng Y, Wang J, Khatib M, Jiang X, Zhou C, Omar R, Saliba W, Wu W, Yuan M, Cui D, Haick H. Highly efficient self-healing multifunctional dressing with antibacterial activity for sutureless wound closure and infected wound monitoring. Adv Mater, 2022, 34(3): 2106842

[43] Cheng B, Zhou J, Wang X, He Z, Xu Z, Wang J, Chen J, Zhu Z, Zhao W, Wan Q, Pei X. Dual-responsive metal polyphenol network nanosheets for diabetic wound healing. Chem Eng J, 2024, 494 153071

[44] Zhang Z, Mi B, Liao Y, Bu P, Xie X, Yu C, Hu W, Sun Y, Feng Q, Liu M, Xue H, Liu G. Mulberry-inspired tri-act hydrogel for visual monitoring and enhanced diabetic wound repair. Chem Eng J, 2025, 505 159313

[45] Dai F, Zhang J, Chen F, Chen X, Lee CJ, Liang H, Zhao L, Tan H. A multi-responsive hydrogel combined with mild heat stimulation promotes diabetic wound healing by regulating inflammatory and enhancing angiogenesis. Adv Sci, 2024, 11(46): 2408783

[46] Chen L, Zhang L, Zhang H, Sun X, Liu D, Zhang J, Zhang Y, Cheng L, Santos HA, Cui W. Programmable immune activating electrospun fibers for skin regeneration. Bioact Mater, 2021, 6(10): 3218-30

[47] Tehrany PM, Rahmanian P, Rezaee A, Ranjbarpazuki G, Sohrabi Fard F, Asadollah salmanpour Y, Zandieh MA, Ranjbarpazuki A, Asghari S, Javani N, Nabavi N, Aref AR, Hashemi M, Rashidi M, Taheriazam A, Motahari A, Hushmandi K. Multifunctional and theranostic hydrogels for wound healing acceleration: an emphasis on diabetic-related chronic wounds. Environ Res, 2023, 238 117087

[48] Cai Y, Chen K, Liu C, Qu X. Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns. Bioact Mater, 2023, 28: 243-54

[49] Wang Y, Ying T, Li J, Xu Y, Wang R, Ke Q, Shen SGF, Xu H, Lin K. Hierarchical micro/nanofibrous scaffolds incorporated with curcumin and zinc ion eutectic metal organic frameworks for enhanced diabetic wound healing via anti-oxidant and anti-inflammatory activities. Chem Eng J, 2020, 402 126273

[50] Lian C, Liu J, Wei W, Wu X, Goto T, Li H, Tu R, Dai H. Mg-gallate metal-organic framework-based sprayable hydrogel for continuously regulating oxidative stress microenvironment and promoting neurovascular network reconstruction in diabetic wounds. Bioact Mater, 2024, 38: 181-94

[51] Cao Y, Chen B, Liu Q, Mao Y, He Y, Liu X, Zhao X, Chen Y, Li X, Li Y, Liu L, Guo C, Liu S, Tan F, Lu H, Liu J, Chen C. Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment. Bioact Mater, 2024, 42: 32-51

Funding

National Natural Science Foundation of China(52072023)

Natural Science Foundation of Beijing Municipality(ZK20240159)

Beijing Science and Technology Planning Project(Z221100007422120)

Fundamental Research Funds for the Central Universities(buctrc202319)

Interdisciplinary Research Center of Beijing University of Chemical Technology(XK2025-05)

RIGHTS & PERMISSIONS

The Author(s)