Design,Synthesis And Application Of Electrostimulation-responsive Biomaterials Based On Hyperbranched Polyamidoamines

Hyperbranched polyamidoamine has garnered significant interest in the polymer field due to its distinctive structure and properties.Positioned between linear and dendritic polymers,it boasts unique physical and chemical characteristics like numerous intramolecular cavities,abundant terminal groups,high solubility,biocompatibility,low viscosity,and non-crystallization.In comparison to linear polymers,hyperbranched polyamide amines exhibit a closer resemblance to dendritic polymers but are simpler to synthesize.Over the last three decades,there has been notable advancement in the synthesis,structural analysis,and functionalization of hyperbranched polyamide amines.Presently,the synthesis techniques for hyperbranched polyamide amine biomaterials have become more comprehensive and refined,setting the stage for practical applications.Nonetheless,there remain unresolved challenges.For instance,in the post-New Coronavirus pandemic era,there has been a heightened focus on antimicrobial materials across various sectors.Traditional hyperbranched polyamide-amine biomaterials lack resistance to microorganisms like molds,bacteria,and viruses,despite their favorable biocompatibility.In the realm of drug/nano-ion delivery,hyperbranched polyamide amines are known for their numerous cavities that make them effective carriers.However,achieving precise,on-demand,controlled release behavior remains a challenge.This thesis focuses on the design and synthesis of a series of multi-performance biomaterials based on hyperbranched polyamide amines.By incorporating functional viologen monomers,these biomaterials were modified to maintain biocompatibility while enhancing antimicrobial,electrochemical,electrochromic/electrocontrollable fluorescence properties.This modification also allows for better control over drug content and release time.The resulting biomaterials exhibit excellent controllability of drug content and release time.The paper contains three major works as follows:(1)Through macromolecular design and synthesis technology,two electroactive hyperbranched polyamidoamine biomaterials were successfully prepared using the one-step Michael addition method and subsequent modification strategies.In the first section of work,under milder conditions,N,N’-methylenebisacrylamide and1,1’-bis(3-aminopropyl)-4,4’-bipyridine bis(bromide)synthesized an electroactive hyperbranched polyamidoamine biomaterial through one-step Michael addition polymerization in methanol/water mixture.Due to the multifunctional viologen groups,hyperbranched polyamidoamine exhibits high electrical activity,excellent electrochromic and electronically controlled fluorescence properties at low voltage(-1.2 ～ 0 V).And the biological material was used to prepare a dual-mode water-phase device with reversible color change and controllable fluorescence conversion characteristics.Finally,the antibacterial properties and biocompatibility of the electroactive hyperbranched polyamidoamine biomaterial were explored,proving that the material maintains biocompatibility and has excellent antibacterial properties.In the second section of the study,by combining Michael addition reaction and terminal modification strategy,we successfully designed and synthesized an innovative multifunctional hyperbranched polyamine.The polymer has electroactive viologen groups embedded in it and is end-capped with hydrophobic adamantane units.We used tertiary amines,adamantane and viologen as functional units to construct an advanced polymer system that can respond intelligently to external stimuli.These functional units endow the polymer with sensitivity to changes in pH,temperature and electric potential,giving it the ability to respond multiple times to color changes and fluorescence changes.These multiple response properties are mainly achieved through conformational changes in the polymer backbone,reversible aggregation and depolymerization behaviors under different conditions,and timely adjustments to the molecular structure.(2)In the context of designing multifunctional biomaterials,a series of EHP/PAM hydrogels were synthesized with electroactive hyperbranched polyamide amine(EHP)serving as the cross-linking agent.These hydrogels exhibited exceptional mechanical properties,including high tensile strength,desirable stretchability(up to 1280%),and stable adhesion.The viologen cation conferred antimicrobial properties and good ionic conductivity to the material,while the reversible redox behavior of viologen imparted electrochromic/electrofluorescent properties.Moreover,the biocompatibility of the material,along with viologen’s quaternary ammonium salt,suggests potential for wearable strain sensing applications.Experimental evidence supports the hydrogel’s excellent reproducibility and sensitivity in the strain range of 1-1000%,facilitating reliable and accurate detection of human body movement upon skin adhesion.The controlled doping and de-doping of viologen under an applied electric field enabled precise electrical control of drug release,with the hydrogel exhibiting 81.6% drug release efficiency at a low voltage of-1.2 V.Additionally,the EHP hydrogel demonstrated pH-stimulated drug release behavior in both acidic and alkaline environments due to significant conformational transitions.Through strategic design,the development of this biomaterial with pH/electrically dual-stimulated drug release properties and wearable strain sensing capabilities opens new possibilities for personalized health diagnosis and treatment.This innovation not only promises immediate health feedback for the wearer but also enables visual monitoring and precise drug release,offering patients more convenient and effective health management solutions.(3)Starting from the concept of “more portable,smarter,and more efficient”,the electroactive hyperbranched polyamidoamine hydrogel biomaterial was further optimized.The introduction of phenylboronic acid and PVA generates a large number of hydrogen bonding,ionic bonding and dynamic covalent bonding sites,which achieves a toughening effect,increases the cycle life of the material,and gives the hydrogel material better mechanical properties.At the same time,the hydrogel also has adjustable ionic conductivity and electrochromic properties,excellent biocompatibility and antibacterial capabilities.Combining the unique structural characteristics of viologen and the excellent drug encapsulation ability of hyperbranched polyamidoamine,the hydrogel is designed to be an electroactive drug storage library that can store two drugs at the same time: Dex(Dexamethasone: an anti-inflammatory and anti-allergic drug).and Ta(Tannin: an antioxidant and pro-apoptotic drug).The hydrogel was further designed as the cathode of the flexible wearable biopatch,the magnesium sheet was used as the anode,the PVA/PBS hydrogel was used as the electrolyte,and PET/ITO was used as the current collector for layer-by-layer assembly to prepare an integrated,visualized,convenient wearable drug release system biopatch.The biopatch has stable and ultra-long controlled drug release behavior,and at the same time,the release status can be monitored through a visualization window.Through psoriasis mouse model experiments,the performance of a dual-drug wearable biopatch was compared with two single-drug controlled-release biopatches.After 5 days of treatment comparison,it was proved that the dual-drug patch overcomes the limitations of single-drug treatment and achieves better results in the treatment of psoriasis.In summary,we first used the advanced concepts of molecular design and synthesis technology to fully utilize the modifiable properties of hyperbranched polyamidoamines,and successfully synthesized two new types of electroactive macromolecules.Both macromolecules offer excellent visualization,and the second material achieves multi-stimulus responsiveness,bringing innovative electroactive biomaterials to the biomedical field.Furthermore,through material design,a hydrogel material with multiple functions was prepared.This hydrogel material not only has a high degree of biocompatibility and adjustability,but can also achieve precise positioning and controlled release of drugs during the treatment process,significantly improving the treatment effect and providing opportunities for the development of personalized medical equipment.Strong material base.Finally,combined with actual clinical needs,a portable,highly intelligent,and efficient drug release patch was designed and prepared.This drug release patch is not only convenient to use,but also can realize real-time monitoring and precise control of drug release,providing new ideas and methods for the research of real-time monitoring and precise controlled release of biological materials.These innovative research results not only expand the application fields of electroactive biomaterials,but also provide important material technology support for high-performance,multi-functional personalized medical devices,which have broad development prospects and practical value.