负载 ZIF-8的GelMA 水凝胶制备及其药物缓释性能和抑菌作用评价

doi:10.13481/j.1671-587X.20240113

Abstract

Abstract:

objective To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8 （ZIF-8），and to evaluate its in vitro cytotoxicity， drug release capability， and antimicrobial propertie. Methods The ZIF-8 particles were synthesized by hydrothermal method， and the microstructure characteristic was observed under scanning electron microscope （SEM）. The particles were mixed with the gelatin methacryloyl （GelMA） with the mass fraction of 0.2% to obtain the composite hydrogel GelMA-Z. The atomic absorption spectroscope was used to detect the cumulative zinc ion （Zn²⁺） release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1， 3， and 7 d；the viabilities of the cells in various groups were detected by CCK-8 assay； the GelMA-Z was co-cultured with Escherichia coli （E. coli） and Staphylococcus aureus （S. aureus） for 6，12，and 24 h and divided into control group， GelMA group， and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader； the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method. Results The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn²⁺ in GelMA-Z showed an initial burst phase within 1 d， followed by a slow release，and reached the equilibrium around 7 d.Compared with control group，the viabilities the cells in GelMA group and GelMA-Z group were above 90% on the 1st， 3rd， and 7th days， but there was no significant difference（P>0.05）.The bacterial activity detection results showed that when co-cultured with bacteria for 6，12，and 24 h， compared with control group and GelMA group，the bacterial activities of the E. coli and S. aureus in GelMA-Z group were decreased （P<0.05）. The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group. The live/dead bacterial staining results showed that in GelMA-Z group，there was a large number of red fluorescence stained dead bacteria； in control group and GelMA group， there was a large number of green fluorescence stained live bacteria. Conclusion The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn²⁺ release capability and antimicrobial activity， and it is a novel hydrogel dressing for treatment of the infected wounds.

Key words: Zeolite imidazole framework-8, Gelatin methacryloyl, Hydrogel, Infected wound, Antibacterial property

CLC Number:

R318.08

Kongzhao JIANG,Chiyu LI,Yungang LUO,Zhihui LIU. Preparationof GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect[J].Journal of Jilin University(Medicine Edition), 2024, 50(1): 106-112.

Figures/Tables 7

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References 25

1	WELLS A， NUSCHKE A， YATES C C. Skin tissue repair： matrix microenvironmental influences［J］. Matrix Biol， 2016， 49： 25-36.
2	DĄBROWSKA A K， SPANO F， DERLER S， et al. The relationship between skin function， barrier properties， and body-dependent factors［J］. Skin Res Technol， 2018， 24（2）： 165-174.
3	SEEBAUER C， LUCAS C， KINDLER S， et al. Wound management-biology and wound healing disorders［J］. Ophthalmologe， 2019， 116（6）： 585-596.
4	REINKE J M， SORG H. Wound repair and regeneration［J］. Eur Surg Res， 2012， 49（1）： 35-43.
5	FRANCESKO A， PETKOVA P， TZANOV T. Hydrogel dressings for advanced wound management［J］. Curr Med Chem， 2018， 25（41）： 5782-5797.
6	HAMEDI H， MORADI S， HUDSON S M， et al. Chitosan based hydrogels and their applications for drug delivery in wound dressings： a review［J］. Carbohydr Polym， 2018， 199： 445-460.
7	LIANG Y P， HE J H， GUO B L. Functional hydrogels as wound dressing to enhance wound healing［J］. ACS Nano， 2021， 15（8）： 12687-12722.
8	QU J， ZHAO X， LIANG Y P， et al. Antibacterial adhesive injectable hydrogels with rapid self-healing， extensibility and compressibility as wound dressing for joints skin wound healing［J］. Biomaterials， 2018， 183： 185-199.
9	ZHENG J F， ZHAO F J， ZHANG W， et al. Sequentially-crosslinked biomimetic bioactive glass/gelatin methacryloyl composites hydrogels for bone regeneration［J］. Mater Sci Eng C Mater Biol Appl， 2018， 89： 119-127.
10	LIU Y X， CHAN-PARK M B. A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture［J］. Biomaterials， 2010， 31（6）： 1158-1170.
11	VAN DEN STEEN P E， DUBOIS B， NELISSEN I， et al. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 （MMP-9）［J］. Crit Rev Biochem Mol Biol， 2002， 37（6）： 375-536.
12	JIANG G Y， LI S H， YU K， et al. A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model［J］. Acta Biomater， 2021， 128： 150-162.
13	KURIAN A G， SINGH R K， PATEL K D， et al. Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics［J］. Bioact Mater， 2021， 8： 267-295.
14	XIAO S N， ZHAO T F， WANG J K， et al. Gelatin methacrylate （GelMA）-based hydrogels for cell transplantation： an effective strategy for tissue engineering［J］.Stem Cell Rev Rep，2019，15（5）：664-679.
15	NAZIR F， ASHRAF I， IQBAL M， et al. 6-deoxy-aminocellulose derivatives embedded soft gelatin methacryloyl （GelMA） hydrogels for improved wound healing applications： in vitro and in vivo studies［J］. Int J Biol Macromol， 2021， 185： 419-433.
16	HUEMER M， MAIRPADY SHAMBAT S， BRUGGER S D， et al. Antibiotic resistance and persistence-Implications for human health and treatment perspectives［J］. EMBO Rep， 2020， 21（12）： e51034.
17	YAO S， CHI J J， WANG Y T， et al. Zn-MOF encapsulated antibacterial and degradable microneedles array for promoting wound healing［J］. Adv Healthc Mater， 2021， 10（12）： e2100056.
18	XIA X M， SONG X J， LI Y， et al. Antibacterial and anti-inflammatory ZIF-8@Rutin nanocomposite as an efficient agent for accelerating infected wound healing［J］. Front Bioeng Biotechnol， 2022， 10： 1026743.
19	DENG L L， HUANG Y J， CHEN S Y， et al. Bacterial cellulose-based hydrogel with antibacterial activity and vascularization for wound healing［J］. Carbohydr Polym， 2023， 308： 120647.
20	LIU Y H， ZHU Z， PEI X B， et al. ZIF-8-modified multifunctional bone-adhesive hydrogels promoting angiogenesis and osteogenesis for bone regeneration［J］. ACS Appl Mater Interfaces，2020，12（33）：36978-36995.
21	CHEN C Y， YIN H， CHEN X， et al. Ångstrom-scale silver particle-embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation［J］. Sci Adv， 2020， 6（43）： eaba0942.
22	JABEEN M， BISWAS P， ISLAM M T， et al. Antiviral peptides in antimicrobial surface coatings-from current techniques to potential applications［J］. Viruses， 2023， 15（3）： 640.
23	BREIJYEH Z， KARAMAN R. Design and synthesis of novel antimicrobial agents［J］.Antibiotics，2023，12（3）： 628.
24	ZHANG Y， CHANG M L， BAO F， et al. Multifunctional Zn doped hollow mesoporous silica/polycaprolactone electrospun membranes with enhanced hair follicle regeneration and antibacterial activity for wound healing［J］. Nanoscale， 2019，11（13）：6315-6333.
25	SAMANI S， HOSSAINALIPOUR S M， TAMIZIFAR M， et al. In vitro antibacterial evaluation of Sol-gel-derived Zn-， Ag-， and （Zn + Ag）-doped hydroxyapatite coatings against methicillin-resistant staphylococcus aureus［J］. J Biomed Mater Res A， 2013， 101（1）： 222-230

Time	Cumulative release amount of Zn²⁺
0 h	0
12 h	0.55±0.03
1 d	0.91±0.02
3 d	1.07±0.02
7 d	1.19±0.03

Group	Survival rate
Group	（t/d） 1	3	7
Control	100.00±0.00	100.00±0.00	100.00±0.00
GelMA	98.21±0.26	98.26±0.49	99.11±0.51
GelMA-Z	97.23±1.17	97.33±0.89	98.75±0.55

Group	Activity of E. coli
Group	（t/h） 0	6	12	24
Control	0.23±0.01	0.72±0.03	0.95±0.08	1.02±0.06
GelMA	0.23±0.01	0.71±0.03	0.96±0.06	1.01±0.07
GelMA-Z	0.23±0.01	0.24±0.01^*△	0.25±0.02^*△	0.24±0.02^*△

Group	Activity of S. aureus
Group	（t/h） 0	6	12	24
Control	0.24±0.02	0.76±0.03	1.02±0.07	1.13±0.03
GelMA	0.24±0.02	0.77±0.03	1.03±0.04	1.12±0.08
GelMA-Z	0.24±0.02	0.25±0.02^*△	0.25±0.05^*△	0.24±0.04^*△

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Preparationof GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect

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