细胞介导交联实现力学增强型可注射水凝胶用于高效细胞递送

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中图分类号:R318.08 文献标志码:A

Cell-Mediated Crosslinking Enables Mechanically Robust Injectable Hydrogel for Efficient Cell Delivery

YU Longkang1.23,ZANG Jing1.23,ZHANGJianhang1.23,HUANG Wei1.2.3,GAO Hongjie1.2.3,ZHANG Yihui2.3, CHEN Mingyu1,2.3, QIAO Lei1,2.3, YOU Yezi1.2,3,WANGLonghai1.2.3 (1. Intellgent ,2.Shol Materals Science;2.TheFirst Affiliated Hospital USTC, University Science Technology China,Hefei 23o026, China)

Abstract:Injectablehydrogelsholdsignificantpromiseforcelltherapy.However,theirclinicaltranslationistenhidered byinsuficient mechanical strengthundesirable foreignbody responses (FBR)in vivo.Inspired bythereinforcement mechanism styrene-butadiene-styrene(SBS)elastomers,acell-mediated covalent croslinking strategy forconstructinga hybrid injectable hydrogelsystemis proposed.This hydrogelisformedviainsitureactionbetweenprimaryaminegroupson thesurfaceislet-like MN6cellaggregates amino groupsona well-hydratedcopolypeptide,mediatedbya bifunctional croslinker,bis-N-hydroxysuccinimide polyethyleneglycol (NHS-PEG-NHS).Bymimicking the polystyreneaggregation domainanchoringobserved in SBSelastomers,theincoporationcell-mediated croslinking pointsnotonlyenables gentle in situecapsulationviablecellclusters,butalsosignificantlyenhances compressivemodulusswellingresistance the hydrogel. The copolypeptide is synthesized via ring-opening polymerization L -serine, D -serine, L -lysine, initiated by lithiumhexamethyldisilazide.Theresulting polymerfeaturesahydrophilic,non-fouling backbone enriched withamide hydroxyl groups,providingastrong“dual hydrogen-bond hydration”efect.This structure imparts excelentbiocompatibility antifouling properties,minimizing immunecellrecruitmentatthe host-materialinterface,therebysupportingthe longtermviability encapsulatedcels.Invivo subcutaneousimplantation in C57BL/6 micereveals that the peptide-based hydrogels induce onlymild inflammatoryresponses,asevidenced bylowpro-inflammatorycytokine expression,reduced macrophage acumulation, minimal collgencapsule formation.Theseresults demonstrate that the proposed cellmediatedcrosslinked hydrogel fersaversatileplatformcombining ijectability,mechanical robustnesscytocompatibility, immunomodulatorycapacityfor effectivecell encapsulation delivery in biomedical applicationssuch as islet transplantation cell-based therapies.

words: injectable hydrogel;;cell-mediated croslinking;mechanicalenhancement;celldelivery;biocompatibility

天然细胞外基质(ECM)为细胞提供了支持结构和生理微环境,但其复杂的生化组成与异质的物理性质限制了其在临床中的直接应用凹。(剩余20034字)

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