title: Substrate-Independent Robust and Heparin-Mimetic Hydrogel Thin Film Coating via Combined LbL Self-Assembly and Mussel-Inspired Post-Cross-linking.
abstract: In this work, we designed a robust and heparin-mimetic hydrogel thin film coating via combined layer-by-layer (LbL) self-assembly and mussel-inspired post-cross-linking. Dopamine-grafted heparin-like/-mimetic polymers (DA-g-HepLP) with abundant carboxylic and sulfonic groups were synthesized by the conjugation of adhesive molecule, DA, which exhibited substrate-independent adhesive affinity to various solid surfaces because of the formation of irreversible covalent bonds. The hydrogel thin film coated substrates were prepared by a three-step reaction: First, the substrates were coated with DA-g-HepLP to generate negatively charged surfaces. Then, multilayers were obtained via LbL coating of chitosan and the DA-g-HepLP. Finally, the noncovalent multilayers were oxidatively cross-linked by NaIO4. Surface ATR-FTIR and XPS spectra confirmed the successful fabrication of the hydrogel thin film coatings onto membrane substrates; SEM images revealed that the substrate-independent coatings owned 3D porous morphology. The soaking tests in highly alkaline, acid, and concentrated salt solutions indicated that the cross-linked hydrogel thin film coatings owned high chemical resistance. In comparison, the soaking tests in physiological solution indicated that the cross-linked hydrogel coatings owned excellent long-term stability. The live/dead cell staining and morphology observations of the adhered cells revealed that the heparin-mimetic hydrogel thin film coated substrates had low cell toxicity and high promotion ability for cell proliferation. Furthermore, systematic in vitro investigations of protein adsorption, platelet adhesion, blood clotting, and blood-related complement activation confirmed that the hydrogel film coated substrates showed excellent hemocompatibility. Both the results of inhibition zone and bactericidal activity indicated that the gentamycin sulfate loaded hydrogel thin films had significant inhibition capability toward both Escherichia coli and Staphylococcus aureus bacteria. Combined the above advantages, it is believed that the designed heparin-mimetic hydrogel thin films may show high potential for applications in various biological and clinical fields, such as long-term hemocompatible and drug-loading materials for implants.
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Ma
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Chao
authors.initials: C
authors.lastname: He
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Chuanxiong
authors.initials: C
authors.lastname: Nie
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Shudong
authors.initials: S
authors.lastname: Sun
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering and ‡National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610065, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000327:Adsorption; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D040761:Biomimetic Materials / Q000494:pharmacology*; D049872:Bivalvia / Q000737:chemistry*; D002417:Cattle; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004298:Dopamine / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D010314:Partial Thromboplastin Time; D056951:Photoelectron Spectroscopy; D010973:Platelet Adhesiveness / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D005839:Gentamicins; D014867:Water; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012710:Serum Albumin, Bovine; D004317:Doxorubicin; D005340:Fibrinogen; D006493:Heparin; D004298:Dopamine
keywords: LbL self-assembly; hemocompatible and antimicrobial coating; heparin-mimetic hydrogel film; mussel-inspired chemistry