Application of Phage Hydrogels in the Medical Field
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摘要: 抗生素滥用引发的细菌耐药危机，导致感染性疾病久治难愈，严重危害人类健康。噬菌体凭借精准靶向病原菌、生物相容性良好等优势，成为极具潜力的新型抗菌策略，但噬菌体的应用易受各类生物屏障干扰。水凝胶凭借良好的生物相容性以及优异的包载能力，成为噬菌体理想载体，实现噬菌体的稳定储存、抗屏障递送和按需释放。本文系统论述噬菌体水凝胶在胃肠道、皮肤及软组织、骨与关节、尿路感染方面的研究进展，分析临床转化面临的瓶颈，展望未来噬菌体水凝胶发展方向，为噬菌体水凝胶的深入研究与临床转化提供理论支撑与参考。Abstract: The bacterial resistance crisis driven by antibiotic misuse has made infectious diseases increasingly difficult to treat and poses a serious threat to human health. Bacteriophages, owing to their precise targeting of pathogenic bacteria and favorable biocompatibility, represent a highly promising novel antibacterial strategy; however, their therapeutic application is often impeded by various biological barriers. Hydrogels, with favorable biocompatibility and excellent encapsulation capability, are ideal carriers for bacteriophages, enabling stable storage, delivery across biological barriers, and on-demand release of bacteriophages. This review systematically summarizes research advances in bacteriophage hydrogels for the treatment of gastrointestinal infections, skin and soft tissue infections, bone and joint infections, and urinary tract infections; analyzes the bottlenecks hindering their clinical translation; and outlines future development directions, with the aim of providing theoretical support and reference for in-depth research and clinical translation of bacteriophage hydrogels.
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Key words:
- Phages /
- Hydrogels /
- Antibacterial /
- Delivery
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表 1 噬菌体水凝胶在不同感染部位中的应用（1）
Table 1. Application of phage-based hydrogels in various infection sites （1）
感染部位 水凝胶 细菌 噬菌体 研究结论 Alimentary infection Chitosan–Alginate bead hydrogel Escherichiacoli PhageZSEC5 The efficient protective effect ofcore matrix materials in chitosan-alginate bead-encapsulated phage against inactivation by low pH，and to sustain bacteriophage rele-ase and lysis activityovertime[29]. Alginate /κ-Carrageenanmicrocapsuleshydrogel Salmonella Typhimurium PhageSL01 The phage core matrix material encapsulated by ALG/CG microc-apsules has a protective effect onphage inactivation underlow pH conditionand can maintain therele-ase and lysis activity of phage over time[30]. Sodium Alginate-Hyaluronic Acid-EudragitS100 Microspheres hydrogel Salmonella Typhimurium LPST83LPST94LPST153 The phage-based Hydrogel protec-ts phages from gastric conditions，prolongs intestinal retention，and enables responsive payload releasein the colon[31]. Skin and Soft tissue
infectionSodium Alginate/Hyaluronic Acid hydrogel Enterococcusfaecium PhageEF-M80 Phage-loaded hydrogel was in favor of the wound healing proc-ess in the mice model[32]. Sodium Alginate–CarboxymethylCellulose–HyaluronicAcid hydrogel Enterococcusfaecalis PhageSAM-E.f12 Phage-containing hydrogels reduc-ed bacterial load and enhanced wound healing，as shownby impro-ved epithelialization and tissue restoration[33]. Poloxamer407-Carbomer Polymer C934Phydrogel Pseudomonasaeruginosa Phage PHW2 This hydrogel exhibits a sustained-release effect against phages，along with excellent stability and adhesion properties[34]. CarboxymethylcelLulose hydrogel Pseudomonasaeruginosa Phage E21 The phage-loaded hydrogel result-ed in a marked Reduction in Mortality among treated rats and significantly enhanced chealing atthe wound site[35]. Oligoethylene Glycolmethacrylate hydrogel Pseudomonasaeruginosa Phage vB_Pae-TiblisiM32 The resulting phage-hydrogel has suitable mechanical strength and stability for use as a burn wounddressing[36]. Carbopol 940 hydrogel Carbapenem-resistant Acinetobacterbaumannii Phage VB_ST-SA173 The hydrogel of the phage lysatedemonstrated lytic activity andsignificantly accelerated wound healing[37]. Carbopol 940 hydrogel Carbapenem-resistant Acinetobacterbaumannii Phage VB_AB_Acb75 The phage-based hydrogel displa-yed lytic activity against infected burn wounds with a marked improvement in wound healing[38]. PolyvinylAlcohol hydrogel ESKAPE Bacteriop-hage suspension The clinical experience indicates the efficacy andsafety of the topical application of bacteriopha-ges in a hydrogel for the sanati-on of burn wounds[39]. 
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1 噬菌体水凝胶在不同感染部位中的应用（2）
1. Application of phage-based hydrogels in various infection sites （2）
感染部位 水凝胶 细菌 噬菌体 研究结论 Bone and Joint Infection Defensive AntibacteriaCoating hydrogel Staphylococcusaureus PP1493、PP1815 This case demonstrated the feasi-bility of the use of bacteriophag-es within a hydrogelto treat pati-ents for knee megaprosthesis infection[40]. Poly（ethylene glycol）-4-maleimide hydrogel Pseudomonasaeruginosa ΦPaer4、ΦPaer14、ΦPaer22、ΦW2005A The bacteriophage-encapsulating hydrogel significantly reduced P. aeruginosa infection in a mur-ine radial defect model[41]. DefensiveAntibacterialCoating hydrogel Escherichia coli、Enterococcusfaecium Intesti Phage The integration of phage therapywith established surgical procedu-res resulted in successful infectioneradication and reconstruction[42]. Alginate-Nanohydroxyapat-ite hydrogel E. faecalis Phage vB_EfaS_LM99 Effective antimicrobial activity and large diffusion of phages LM99 from hydrogels were obse-rved，inhibiting attachment and growth of planktonic[43]. Poly（ethylene glycol）-based hydrogel Pseudomonasaeruginosa Phage ΦPaer4 Bacteriophage delivery significant-ly reduces viable bacteria in a chronic implant infection model，providing proof of concept for their feasibility asan antimicrobialstrategy[44]. Urinarytra-ct infection Hydrogel-coated Pseudomonasaeruginosa Phage M4 The pretreatment of hydrogel-coated silicone catheters with P. aeruginosa phage M4 signific-antly reduced attachment and bio-film formation by P. aeruginosa M4 in a laboratorymodel system[45]. Hydrogel-coated E. coli P. mirabilis Phage T4 Lytic bacteriophages may be not only in the prevention of biofilmformationby bacteria but also in the destruction/eradication of esta-blished biofilms[46]. Hydrogel-coated P. aeruginosP. mirabilis Phage cocktails Pretreatment of a hydrogel urina-ry catheter with a phage cocktail can significantly reduce mixed-speciesbiofilm formation by clini-cally relevant bacteria[47]. Poly（vinyl alcohol）hydrogel P. mirabilis Lytic phage The phage-based hydrogel coatingcan release a thera-peutic dose ofbacteriophage in response to elev-ated urinary pH，in order to delay catheter blockage[48].
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