Mussel-inspired Polydopamine Hybridized Functional Material Incorporated Hydrogel For Biomedical Applications

Hydrogels are promising candidates in biomedical applications due to their flexibility,high water-content,and adjustable modulus.However,traditional hydrogels usually display brittle mechanical performance and feature a unitary function,and therefore cannot satisfy the performance requirements for various applications.Precision design of hydrogel molecular network by incorporating functional materials can endow hydrogels with multifunction,such as conductivity,stability,and tissue/cell affinity.However,the inherent characteristics of most functional materials make it difficult to effective combine with hydrogel networks.For example,graphene and conductive polymers are intrinsically hydrophobic that cannot be well dispersed in the hydrogel matrix;natural polymeric gelatin and cellulose exhibit strong intermolecular interaction that cannot be well integrated with other functional materials.Recently,polydopamine,with similar structure as that of mussel-secreted adhesive proteins,plays an outstanding performance in enhancing the hydrophilicity,biocompatibility,and cell affinity of functional materials,which has been widely used in the synthesis of multifunctional hybrid materials.Based on the mussel chemistry,this study developed a series of biomedical hydrogels by incorporating polydopamine hybridized functional materials into the polymer matrix,which exhibited excellent mechanical performance and biological functions.The main content includes the following parts:(1)The polydopamine was utilized to regulate the polymerization of pyrrole to form polydopamine-hybridized polypyrrole nanocomposite(PDA-PPy)with hydrophilicity.Then,a transparent,stretchable,self-adhesive,and conductive hydrogel was obtained(PDA-PPy-PAM)by in situ formation of PDA-PPy nanofibrils in the polyacrylamide(PAM)network.The in situ formed PDA-PPy nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh,which created a complete conductive path and endowed the hydrogel with excellent conductivity(12 S/m).The interwoven nanofibrils allowed visible light to pass through,thus improving the transmittance of hydrogels(70%).This nanostructure network can uniformly distribute stress,share load and dissipate energy during hydrogel deformation,and therefore the hydrogel showed a high elongation of 2000%and fracture energy of 3000 J/m~2.The transparent hydrogel only transmitted visible light but cut off UV light owing to the ability of PDA-PPy to absorb UV light.As demonstrated by an in vivo animal experiment,the rat skin protected by the hydrogel was intact after 20 min of UV radiation(30 m W/cm~2,365 nm).Moreover,the PDA-PPy nanofibrils with abundant catechol groups imparted the hydrogel with self-adhesiveness.Consequently,the hydrogel was designed as self-adhesive electrodes to adhere to human body for biosignals detection.Meanwhile,the hydrogel with high transparency facilitated medical personnel to observe the skin thought the hydrogel during detection.The fabricated multifunctional hydrogel shows promise in a range of applications,such as transparent electronic skins,flexible wearable electronic devices,wound dressings.(2)The polydopamine-reduced-graphene oxide(PGO)was used as a template to intercalate the microcrystalline cellulose and guide the self-assembly of cellulose nanocrystals on its surface to form cellulose-derived conductive 2D bio-nanosheets(PGC)nanosheets with biostability and biocompatibility.Then,a flexible,biostable,conductive,and cell/tissue affinitive hydrogel(PGCNSH)was obtained by physical self-assembly and chemical crosslinking of the PGC nanosheets.The physical interactions mediated self-assembly and the epichlorohydrin induced chemical crosslinking reinforced the toughness(1200 J/m~2)and tensile strength(136 k Pa)of PGCNSH hydrogels.The assembled PGC nanosheets with intrinsic conductivity constructed a continuous and well-connected 3D network,thereby guaranteeing high conductivity(6 S/m)of the hydrogel.In addition,the strong interactions between cellulose and PGO in PGC nanosheets effectively restricted the relaxation of the cellulose chains,and therefore the PGCNSH hydrogels exhibited stable electrical and mechanical performances.Thus,the bioelectronic devices are able to stably record electrophysiological signals after undergoing aqueous immersion and in vivo implantation for30 days.In vitro cell culture experiments demonstrated that the PGCNSH hydrogel with excellent cell affinity served as a cell stimulator,which could respond to external electrical stimulation to regulate the proliferation,adhesion and differentiation of cells.In vivo experiments further indicated that the PGCNSH hydrogel could accelerate diabetic wound healing through electrotherapy.The formation of ultra-biostable conductive hydrogel based on the nanosheet-assembled method lays a foundation for designing implantable and flexible bioelectronic devices.(3)The polydopamine was used to hybridized with gelatin(Gel)chains to form adhesive PDA/Gel complex.Then,the PDA/Gel complex was incorporated into an elastic polyacrylic acid(PAA)hydrogel matrix to fabricate the strong,tough,tissue adhesive,and cell affinitive polydopamine/gelatin-poly(acrylic acid)(PDA/Gel-PAA)composite hydrogel for cartilage repair.The hydrogel achieved high compressive strength up to 0.67 MPa and toughness of 420J/m~2,which can meet the mechanical requirements of cartilage regeneration.The carboxyl groups in the hydrogel matrix mimicked the negatively charged glycosaminoglycan in the nature cartilage extracellular matrix(ECM),which provided a suitable microenvironment for cartilage regeneration.In addition,the incorporation of adhesive PDA/Gel complex provided adhesive sites to improve the tissue/cell affinity of hydrogels.In vitro experiments proved that the PDA/Gel-PAA hydrogel favored the proliferation and adhesion of bone marrow stem cells,and directed the chondrogenic differentiation after the hydrogel combined with growth factor(TGFβ3).In vivo experiments demonstrated that the adhesive hydrogel can integrate well with surrounding tissues after implantation,thereby promoting cartilage regeneration.