| Hydrogels are increasingly utilized in biomedical fields due to their distinct bionic microenvironment,characterized by high-water content,adjustable physical and chemical properties,and excellent biocompatibility.Among these,injectable hydrogels,capable of direct delivery to targeted body areas through minimally invasive injection methods,have garnered significant attention.Current research has increasingly focused on injectable supramolecular hydrogels formed through non-covalent interactions.However,most non-covalent interactions suffer from drawbacks such as poor selectivity or the requirement of harsh gel-forming conditions,limiting the potential applications of these hydrogels.Host-guest interactions present a viable solution to overcome these limitations.These interactions occur through reversible non-covalent interactions between two mutually recognizing molecules.Notably,the host-guest interactions between β-cyclodextrin(βCD)and adamantane(Ad)offer advantages such as mild reaction conditions,high association constants,and self-healing efficiency.Consequently,biomaterials based on this host-guest interaction hold broad application prospects in the biomedical field,including cell culture scaffold,minimally invasive injection,and three-dimensional(3D)bioprinting.In this thesis,using the host-guest interactions of βCD/Ad,four injectable supramolecular hydrogels were successfully constructed by rationally designing the host-guest polymer chains and the hydrogel structures.The study encompasses the functionalization of polymers as well as the investigation of physicochemical properties and applications of the hydrogels.The main areas covered in this thesis are as follows:(1)PMM-βCD/PAAm-Ad injectable supramolecular hydrogels were prepared by using two synthetic polymers and βCD/Ad host-guest interactions.The focus of this study was to explore the design and properties of these injectable hydrogels.β-Cyclodextrin-grafted poly(methyl vinyl ether-maleic acid)(PMM-βCD)and adamantane-grafted polyacrylamide(PAAm-Ad)were prepared by chemical synthesis,respectively.The PMM-βCD/PAAm-Ad supramolecular hydrogels were rapidly obtained by simply mixing two synthetic polymer solutions.The hydrogels exhibited enhanced and tunable mechanical properties by rational combination of host and guest polymers.Notably,they displayed shear-thinning behavior and self-healing properties,making them suitable for injection.Moreover,PMM-βCD/PAAm-Ad-4 hydrogel with a high cross-linking density demonstrated improved resistance to solvent erosion,with a degradation ratio of less than 20% after continuous immersion in PBS for 14 days.Cell experiments revealed that the hydrogels exhibited low cytotoxicity and supported the 3D culture of L929 and SKOV3 cells.However,the cell distribution within the hydrogel was relatively shallow,reaching a height of less than 150μm.Therefore,while the PMM-βCD/PAAm-Ad hydrogel system has achieved the initial goal of developing injectable supramolecular hydrogels,there are still shortcomings that need to be addressed.(2)To improve the cytocompatibility of the fully synthetic polymer hydrogel,a composite Alg-βCD/PAAm-Ad injectable supramolecular hydrogel system,combining natural and synthetic polymers,was designed using alginate with good biocompatibility as the backbone of the host polymer.Firstly,the rheological properties of the hydrogels were analyzed.With an increase in the degree of βCD and Ad substitution,the hydrogels exhibited elevated storage modulus,elasticity,and longer relaxation time,indicating a stronger network structure and improved mechanical properties.Secondly,the encapsulation and 3D culture capabilities of the hydrogels for cells were investigated.The cells within the hydrogels exhibited robust growth and 3D morphology,with a maximum distribution height of 380 μm.This height was over 150% higher compared to the PMM-βCD/PAAm-Ad hydrogel.In summary,this injectable and self-healing hydrogel system demonstrated enhanced 3D cell culture potential.Consequently,this hydrogel system can serve as a scaffold for studying cell behavior in a 3D environment and as a delivery material for transporting cells in vivo.(3)To enhance the adhesion ability of Alg-βCD/PAAm-Ad supramolecular hydrogels,an adhesion-enhancing supramolecular hydrogel system,Alg-βCD-DA/PAAm-Ad,was designed incorporating dopamine as an adhesive functional molecule.Alongside investigating the basic properties of hydrogels,such as rheology,microscopic morphology,and cytocompatibility,the adhesion properties of hydrogels were emphatically studied.Firstly,the hydrogels demonstrated adhesion to various materials,including plastics,steel,and glass,with an impressive adhesion strength of up to 64 k Pa on glass surface.Secondly,the hydrogel’s adhesion strength to tissue was examined using pig skin as a model,which reached a shear strength of 19.2 k Pa,approximately 76% higher than that of the Alg-βCD/PAAm-Ad hydrogel.Forthermore,the injectable ability of the hydrogel was further investigated.When extruded from a 16 G needle at a rate of 2.0 m L/min,the hydrogel only required a moderate injection pressure of 67.4 N,demonstrating its ease of use in practical applications.Consequently,compared to the Alg-βCD/PAAm-Ad hydrogel,this supramolecular hydrogel system with superior adhesion designed in this section significantly expand its potential applications as delivery materials for precise local treatments.(4)To improve the mechanical properties and cell adhesion,a multiple network hydrogel system,Alg-βCD/PAAm-Ad/Gel MA,was developed by a combination of host-guest interactions and covalent bonds.The multiple network includes two aspects: the composite of three natural/synthetic polymers of alginate,polyacrylamide,and gelatin and the hybridization of the two cross-linking mechanisms of host-guest/covalent bond.The hydrogels were prepared using a convenient "one-step gelation method" by initiating free radical polymerization of the Alg-βCD/Ad-AAm/Gel MA pre-gel solution under UV light,facilitating cross-linking between the three polymers.This approach streamlined the experimental steps and resulted in a hydrogel with a more uniform and stable network structure.The hydrogels exhibited various advantages,including p H sensitivity,selfhealing capability,adjustable hydrophilicity,and uniform porosity.Notably,the hydrogel demonstrated favorable mechanical properties,with a maximum tensile strain of 242.8%,tensile strength of 75.9 k Pa,and Young’s modulus of 28.5 k Pa,significantly surpassing those of the pure host-guest cross-linked supramolecular hydrogel mentioned earlier.Biocompatibility assessment revealed excellent cytocompatibility,supporting cell adhesion and spreading,along with good blood compatibility and histocompatibility.Moreover,the pre-gel solution exhibited temperature-adjustable viscosity,with a sol-gel transition point of 20.4 ℃,enabling 3D printing as a bioink.The printed scaffold displayed impressive resilience and toughness.In summary,the Alg-βCD/PAAm-Ad/Gel MA multiple network hydrogel system showed improved mechanical properties,cytocompatibility,and 3D bioprinting capability compared to the aforementioned host-guest cross-linked supramolecular hydrogels,presenting a hydrogel material with good comprehensive properties. |
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