Porous photothermal antibacterial antioxidant dual-crosslinked cryogel based on hyaluronic acid/ polydopamine for non-compressible hemostasis and infectious wound repair

doi:10.1016/j.jmst.2021.12.054

Abstract

Abstract:

Cryogel dressings with good absorption ability and photothermal antibacterial properties for preventing wound infections and treating infected wounds have attracted widespread attention. In this work, a series of cryogels with macroporous structure, antioxidant and photothermal properties were prepared based on adipic dihydrazide modified hyaluronic acid (HA-ADH), and dopamine (DA). The antioxidant properties, hemostatic properties, near infrared (NIR) assisted photothermal antibacterial ability provided by polydopamine, recyclable compression mechanical properties, and cytocompatibility were tested. The results demonstrated that the HA-ADH/DA cryogels have stable mechanical properties, great antibacterial properties against E. coli (EC) and methicillin-resistant S. aureus (MRSA). The high swelling ratio due to the high water retention of HA equipped the cryogels with the capability of absorbing exuded blood and excessive tissue fluid in the infected full-thickness skin defect model of mouse. The cryogels demonstrated good cytocompatibility and antioxidant performance through cell tests and 1, 1-diphenyl-2-methylbenzohydrazino (DPPH) scavenging efficiency test. The cryogels showed enhanced blood-clotting index (BCI) and better hemostatic ability in the mouse liver trauma model and the rat deep non-compressible liver defect model compared with gauze and gelatin sponge. Furthermore, compared with commercial Tegaderm^TM dressing in vivo, the HA-ADH/DA cryogels could greatly promote infected skin wound healing in a full-thickness infected skin defect wound model. In summary, the macroporous HA-ADH/DA cryogels with good antioxidant, high swelling ratio, photothermal antibacterial property, and biocompatibility are a promising hemostatic material and wound healing dressing.

Key words: Dopamine-hyaluronic acid-based cryogels, Antioxidant, Photothermal antibacterial, Wound healing, Hemostasis

Chunbo Wang, Yuqing Liang, Ying Huang, Meng Li, Baolin Guo. Porous photothermal antibacterial antioxidant dual-crosslinked cryogel based on hyaluronic acid/ polydopamine for non-compressible hemostasis and infectious wound repair[J]. J. Mater. Sci. Technol., 2022, 121: 207-219.

Figures/Tables 9

Fig. 1. Preparation route of HA-ADH/DA cryogels, and different fixed shapes cryogels for hemostasis and infected wound healing.

Fig. 2. Swelling ratio and mechanical properties of the cryogels. (a) Swelling ratios of the HA-ADH/DA cryogels. (b) The uniaxial (80% strain) compression stress-strain curves of the cryogels. (c-h) The cyclic (80% strain) compression stress-strain curves of HA-ADH/DA0, HA-ADH/DA2, HA-ADH/DA4, HA-ADH/DA6, HA-ADH/DA8, and HA-ADH/DA10, respectively. (i) First row: The original, compressed, expanded, and re-squeezed pictures of HA-ADH/DA6 cryogel. Second row: Image of HA-ADH/DA6 cryogel swelling in liquid and image of liquid being completely absorbed. Scale bar: 1 cm.

Fig. 3. SEM image of HA-ADH/DA cryogels. (a) The original pore structure of the cryogels after freeze-drying, fixed and compressed pore structure, and the pore structure with shape recovery. Scale bar: 300 μm. (b-g) Pore size distribution of cryogel in its original state.

Fig. 4. Blood compatibility and cell compatibility of cryogel. (a) In vitro hemolysis of cryogel when the concentration of the sample is 2500 μg/mL. P: PBS; 0: HA-ADH/DA0; 2: HA-ADH/DA2; 4: HA-ADH/DA4; 6: HA-ADH/DA6; 8: HA-ADH/DA8; 10: HA-ADH/DA10; T: Triton X-100. Scale bar: 1 cm. (b) Hemolysis ratio of cryogels. (c) L929 cell viability after being treated with different cryogel extractions. (d) The effect of the direct contact method on the proliferation of L929 cells on day 1 and day 3. (e) 3D culture model diagram. (f) The cell proliferation of 3D culture. (g, h) Morphology of L929 cells cultured in HA-ADH/DA6 with Live/dead staining. Scale bar: 100 μm. *p < 0.05, **p < 0.01.

Fig. 5. Hemostatic evaluation of cryogel. (a) SEM images of gauze, gelatin sponge and HA-ADH/DA cryogels in blood cell adhesion and platelet adhesion tests. Scale bar: 30 µm. (b) The data of gauze, gelatin sponge and HA-ADH/DA cryogels dynamic whole blood clotting assay. (c) Schematic representation, (d) blood loss and (e) hemostatic time in the mouse liver trauma model. (f) Schematic representation, (g) blood loss and (h) hemostatic time in the rat liver defect hemorrhage model. *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 6. The ability to scavenge DPPH and photothermal, antibacterial property evaluation of the HA-ADH/DA cryogels. (a) The ability of the HA-ADH/DA cryogels to scavenge DPPH. (b) Temperature enhancement of HA-ADH/DA cryogels under irradiation with power density of 1.4 W/cm2. (c) Temperature enhancement of HA-ADH/DA6 under irradiation with different power density (1.0, 1.4 and 1.8 W/cm2). (d) Photothermal image of HA-ADH/DA cryogels with power density of 1.4?W/cm2. (e) Photographs of the survival EC and (f) MRSA under the NIR irradiation (power density was 1.4 W/cm2). Scale bar: 4 cm. The sterilization ratio-irradiation time curves of (g) EC and (h) MRSA for PBS, HA-ADH/DA0, and HA-ADH/DA6 treatment under the NIR irradiation (power density was 1.4?W/cm2).

Fig. 7. MRSA-infected wound healing effect of different treatments. (a) Photographs of the wounds treated with TegadermTM dressing, HA-ADH/DA0, HA-ADH/DA6 and HA-ADH/DA6+NIR. (b) Wound closure ratio of the different materials treated wounds. (c) H&E staining of wounds on day 3, 7, 14, and 21. The yellow arrow in Fig. 7(c) represents granulation tissue.

Fig. 8. MRSA-infected wound skin tissue remodeling effect of different treatment groups. (a) Epidermal thickness on day 14 and (b) granulation tissue thickness on day 7. (c) Masson staining of wounds on day 14 and 21. The epidermis, dermis, and hypodermis of the skin on day 14. *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 9. Immunofluorescence staining of (a) CD68 and (b) CD31 in the skin tissues on day 3 and day 7. (c, d) Relative fluorescence intensity of CD68 and CD31 in the skin tissues on day 3 and day 7. Scale bar: 100 μm. *p < 0.05, **p < 0.01, ***p < 0.001.

References 81

[1]	D.W. Grainger, Diabetes 64 (2015) 2717-2719. DOI URL PMID
[2]	S.L. Percival, J.G. Thomas, D.W. Williams, Int. Wound J. 7 (2010) 169-175. DOI URL PMID
[3]	T.J. Shaw, P. Martin, J. Cell Sci. 122 (2009) 3209-3213. DOI URL
[4]	D. Milatovic, I. Braveny, Eur. J. Clin. Microbiol. 6 (1987) 234-244. DOI URL PMID
[5]	M. Frieri, K. Kumar, A. Boutin, J. Infect. Public Health 10 (2017) 369-378. DOI URL
[6]	R. Wesgate, P. Grasha, J.Y. Maillard, Am. J. Infect. Control 44 (2016) 458-464. DOI URL
[7]	M. Akova, Virulence 7 (2016) 252-266. DOI URL
[8]	M.K. Rai, S.D. Deshmukh, A.P. Ingle, A.K. Gade, J. Appl. Microbiol. 112 (2012) 841-852. DOI URL PMID
[9]	B.S. Atiyeh, M. Costagliola, S.N. Hayek, S.A. Dibo, Burns 33 (2007) 139-148. DOI URL
[10]	C. Beer, R. Foldbjerg, Y. Hayashi, D.S. Sutherland, H. Autrup, Toxicol. Lett. 208 (2012) 286-292. DOI URL
[11]	C. Marambio-Jones, E.M.V. Hoek, J. Nanopart. Res. 12 (2010) 1531-1551. DOI URL
[12]	X. Dai, Y. Zhao, Y. Yu, X. Chen, X. Wei, X. Zhang, C. Li, ACS Appl. Mater. Inter-faces 9 (2017) 30470-30479.
[13]	S.J. Park, E.B. Kang, S.M. Sharker, G. Lee, I. In, S.Y. Park, Macromol. Mater. Eng. 301 (2016) 141-148. DOI URL
[14]	Y. Yu, P. Li, C. Zhu, N. Ning, S. Zhang, G.J. Vancso, Adv. Funct. Mater. 29 (2019)
[15]	J. Xu, K. Yao, Z. Xu, Nanoscale 11 (2019) 8680-8691. DOI URL
[16]	X. Fan, F. Yang, C. Nie, Y. Yang, H. Ji, C. He, C. Cheng, C. Zhao, ACS Appl. Mater. Interfaces 10 (2018) 296-307. DOI URL
[17]	H. Ji, K. Dong, Z. Yan, C. Ding, Z. Chen, J. Ren, X. Qu, Small 12 (2016) 6200-6206. DOI URL
[18]	A. D’Agostino, A. Taglietti, R. Desando, M. Bini, M. Patrini, G. Dacarro, L. Cucca, P. Pallavicini, P. Grisoli, Nanomaterials 7 (2017)
[19]	D. Hu, H. Li, B. Wang, Z. Ye, W. Lei, F. Jia, Q. Jin, K.F. Ren, J. Ji, ACS Nano 11 (2017) 9330-9339. DOI URL
[20]	S.B. Abel, E.I. Yslas, C.R. Rivarola, C.A. Barbero, Nanotechnology 29 (2018)
[21]	X. Fan, H. Li, W. Ye, M. Zhao, D. Huang, Y. Fang, B. Zhou, K. Ren, J. Ji, G. Fu, Colloids Surf. B 183 (2019)
[22]	Y. Liu, K. Ai, L. Lu, Chem. Rev. 114 (2014) 5057-5115. DOI URL
[23]	C. Liu, W. Yao, M. Tian, J. Wei, Q. Song, W. Qiao, Biomaterials 179 (2018) 83-95. DOI URL
[24]	Y. Liang, M. Li, Y. Huang, B. Guo, Small 17 (2021)
[25]	B. Guo, R. Dong, Y. Liang, M. Li, Nat. Rev. Chem. 5 (2021) 773-791. DOI URL
[26]	M. Shin, J.H. Ryu, K.R. Kim, M.J. Kim, S. Jo, M.S. Lee, D.Y. Lee, H. Lee, ACS Bio-mater. Sci. Eng. 4 (2018) 2314-2318.
[27]	M. Li, Z. Zhang, Y. Liang, J. He, B. Guo, ACS Appl. Mater. Interfaces 12 (2020) 35856-35872. DOI URL
[28]	M.S. Birajdar, K.S. Halake, J. Lee, J. Ind. Eng. Chem. 63 (2018) 117-123. DOI URL
[29]	X. Bao, J. Zhao, J. Sun, M. Hu, X. Yang, ACS Nano 12 (2018) 8882-8892. DOI URL
[30]	X. Zhao, Y. Liang, Y. Huang, J. He, Y. Han, B. Guo, Adv. Funct. Mater. 30 (2020)
[31]	Z. Wang, Y. Duan, Y. Duan, J. Control Release 290 (2018) 56-74. DOI URL
[32]	Y. Liang, X. Zhao, T. Hu, Y. Han, B. Guo, J. Colloid Interface Sci. 556 (2019) 514-528. DOI URL
[33]	Y. Liang, J. He, B. Guo, ACS Nano 15 (2021) 12687-12722. DOI URL
[34]	J.A.P. Gomes, R. Amankwah, A. Powell-Richards, H.S. Dua, Br. J. Ophthalmol. 88 (2004) 821-825. DOI URL
[35]	P.H. Weigel, G.M. Fuller, R.D. LeBoeuf, J. Theor. Biol. 119 (1986) 219-234. URL PMID
[36]	J. Qu, X. Zhao, Y. Liang, Y. Xu, P.X. Ma, B. Guo, Chem. Eng. J. 362 (2019) 548-560. DOI URL
[37]	K.G. Rice, J. Med. Chem. 41 (1998)
[38]	S.K. Hahn, R. Ohri, C.M. Giachelli, Biotechnol. Bioeng. 10 (2005) 218-224.
[39]	P.L. Tran, A.N. Hamood, A. De Souza, G. Schultz, B. Liesenfeld, D. Mehta, T.W. Reid, Wound Repair Regen. 23 (2015) 74-81. DOI URL
[40]	Z. Fan, B. Liu, J. Wang, S. Zhang, Q. Lin, P. Gong, L. Ma, S. Yang, Adv. Funct. Mater. 24 (2014) 3933-3943. DOI URL
[41]	K.A. Rieger, N.P. Birch, J.D. Schiffman, J. Mater. Chem. B 1 (2013) 4531-4541. DOI URL
[42]	X. Yu, L. Guo, M. Liu, X. Cao, S. Shang, Z. Liu, D. Huang, Y. Cao, F. Cui, L. Tian, Int. J. Biol. Macromol. 120 (2018) 2279-2284. DOI URL
[43]	A.E. Stoica, C. Chircov, A.M. Grumezescu, Molecules 25 (2020)
[44]	Y. Huang, X. Zhao, Z. Zhang, Y. Liang, Z. Yin, B. Chen, L. Bai, Y. Han, B. Guo, Chem. Mater. 32 (2020) 6595-6610. DOI URL
[45]	X. Zhao, B. Guo, H. Wu, Y. Liang, P.X. Ma, Nat. Commun. 9 (2018)
[46]	X. Jia, G. Colombo, R. Padera, R. Langer, D.S. Kohane, Biomaterials 25 (2004) 4797-4804. DOI URL
[47]	J. He, M. Shi, Y. Liang, B. Guo, Chem. Eng. J. 394 (2020)
[48]	Y. Huang, X. Zhao, C. Wang, J. Chen, Y. Liang, Z. Li, Y. Han, B. Guo, Chem. Eng. J. 427 (2022)
[49]	Z. Deng, T. Hu, Q. Lei, J. He, P.X. Ma, B. Guo, ACS Appl. Mater. Interfaces 11 (2019) 6796-6808. DOI URL
[50]	T. Kageyama, T. Osaki, J. Enomoto, D. Myasnikova, T. Nittami, T. Hozumi, T. Ito, J. Fukuda, ACS Biomater. Sci. Eng. 2 (2016) 1059-1066. DOI URL
[51]	P.A. Shiekh, A. Singh, A. Kumar, Biomaterials 249 (2020)
[52]	J. He, Z. Zhang, Y. Yang, F. Ren, J. Li, S. Zhu, F. Ma, R. Wu, Y. Lv, G. He, B. Guo, D. Chu, Nano Micro Lett 13 (2021)
[53]	X. Zhao, Y. Liang, B. Guo, Z. Yin, D. Zhu, Y. Han, Chem. Eng. J. 403 (2021)
[54]	J. Qu, X. Zhao, Y. Liang, T. Zhang, P.X. Ma, B. Guo, Biomaterials 183 (2018) 185-199. DOI URL
[55]	M. Li, Y. Liang, J. He, H. Zhang, B. Guo, Chem. Mater. 32 (2020) 9937-9953. DOI URL
[56]	Y. Liang, Z. Li, Y. Huang, R. Yu, B. Guo, ACS Nano 15 (2021) 7078-7093. DOI URL
[57]	P. Li, S. Liu, X. Yang, S. Du, W. Tang, W. Cao, J. Zhou, X. Gong, X. Xing, Chem. Eng. J. 403 (2021)
[58]	J. Li, Y. Wang, J. Yang, W. Liu, Chem. Eng. J. 420 (2020)
[59]	B. Tao, C. Lin, Z. Yuan, Y. He, M. Chen, K. Li, J. Hu, Y. Yang, Z. Xia, K. Cai, Chem. Eng. J. 403 (2021)
[60]	G. Xie, N. Zhou, Y. Gao, S. Du, H. Du, J. Tao, L. Zhang, J. Zhu, Chem. Eng. J. 403 (2021)
[61]	T. Su, M. Zhang, Q. Zeng, W. Pan, Y. Huang, Y. Qian, W. Dong, X. Qi, J. Shen, Bioact. Mater. 6 (2021) 579-588.
[62]	N.W.S. Kam, M. O’Connell, J.A. Wisdom, H. Dai, Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 11600-11605.
[63]	O. Terland, B. Almas, T. Flatmark, K.K. Andersson, M. Sorlie, Free Radic. Biol. Med. 41 (2006) 1266-1271. DOI URL
[64]	A. Ramkissoon, P.G. Wells, Free Radic. Biol. Med. 50 (2011) 295-304. DOI URL
[65]	I. Miyazaki, M. Asanuma, Acta Med. Okayama 62 (2008) 141-150. PMID
[66]	L. Han, P. Li, P. Tang, X. Wang, T. Zhou, K. Wang, F. Ren, T. Guo, X. Lu, Nanoscale 11 (2019) 15846-15861. DOI URL PMID
[67]	I. Bruzauskaite, D. Bironaite, E. Bagdonas, E. Bernotiene, Cytotechnology 68 (2016) 355-369. DOI URL
[68]	B.A. Harley, H.D. Kim, M.H. Zaman, I.V. Yannas, D.A. Lauffenburger, L.J. Gibson, Biophys. J. 95 (2008) 4013-4024. DOI URL
[69]	C.M. Murphy, M.G. Haugh, F.J. O’Brien, Biomaterials 31 (2010) 461-466. DOI URL PMID
[70]	I.C. Lee, Y.T. Lee, B.Y. Yu, J.Y. Lai, T.H. Young, J. Biomed. Mater. Res. A 91 (2009) 929-938. DOI PMID
[71]	S. Thönes, L.M. Kutz, S. Oehmichen, J. Becher, K. Heymann, A. Saalbach, W. Knolle, M. Schnabelrauch, S. Reichelt, U. Anderegg, Int. J. Biol. Macromol. 94 (2017) 611-620. DOI URL PMID
[72]	C.F. Jones, R.A. Campbell, Z. Franks, C.C. Gibson, G. Thiagarajan, A. Vieira-de-Abreu, S. Sukavaneshvar, S.F. Mohammad, D.Y. Li, H. Ghan-dehari, A.S. Weyrich, B.D. Brooks, D.W. Grainger, Mol. Pharmaceut. 9 (2012) 1599-1611. DOI URL
[73]	F. Cheng, C. Liu, X. Wei, T. Yan, H. Li, J. He, Y. Huang, ACS Sustain. Chem. Eng. 5 (2017) 3819-3828. DOI URL
[74]	C. Dai, Y. Yuan, C. Liu, J. Wei, H. Hong, X. Li, X. Pan, Biomaterials 30 (2009) 5364-5375. DOI URL
[75]	J. Luo, C. Liu, J. Wu, L. Lin, H. Fan, D. Zhao, Y. Zhuang, Y. Sun, Mater. Sci. Eng. C 98 (2019) 628-634. DOI URL
[76]	Y. Li, X. Liu, L. Tan, Z. Cui, X. Yang, Y. Zheng, K.W.K. Yeung, P.K. Chu, S. Wu, Adv. Funct. Mater. 28 (2018)
[77]	R. Gharibi, H. Yeganeh, A. Rezapour-Lactoee, Z.M. Hassan, ACS Appl. Mater. In-terfaces 7 (2015) 24296-24311.
[78]	Y. Zhu, Z. Ma, L. Kong, Y. He, H.F. Chan, H. Li, Biomaterials 256 (2020)
[79]	S. Epelman, K.J. Lavine, G.J. Randolph, Immunity 41 (2014) 21-35. DOI URL PMID
[80]	S. Park, T.A. DiMaio, E.A. Scheef, C.M. Sorenson, N. Sheibani, Am. J. Physiol. Cell Physiol. 299 (2010)
[81]	P. Lertkiatmongkol, D. Liao, H. Mei, Y. Hu, P.J. Newman, Curr. Opin. Hematol. 23 (2016) 253-259. DOI URL PMID