Mechanical Properties And Design Of Functionalized Hydrogels

Recently,with the rapid growth of demand for biological and medical applications,soft materials have attracted the attention of more and more researchers.Due to the excellent biocompatibility,hydrogels have been the promising candidate among soft materials.Hydrogels are a kind of elastomers with three-dimensional and micropore network structure.Mechanical properties of hydrogels are critical for their applications.For example,when they serve as articular cartilage regeneration scaffolds,they provide not only the mechanical support,but also the mechanical cues essential to maintain the phenotype of cartilage-forming cells.The design of hydrogels mainly consists of two aspects,the back-bone structure and crosslinking points.The thermodynamic and kinetic properties of the crosslinking interaction are the main factor influencing the mechanical properties of hydrogels.So far,there have been many successful examples of functionalizing hydrogels,however,there are still some problems need to be solved.In order to obtain a more application-oriented hydrogel system,we designed several new functional hydrogels based on the existing methods,including double network hydrogel for cartilage regeneration,strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery,protein based injectable hydrogel and tough hybrid network hydrogel by molecule engineering.We expect that they can function effectively as scaffolds tissue engineering and biological applications.Besides,the design principle may guide future efforts to engineer soft materials with tailored mechanical properties.?1?Double network hydrogel for cartilage regenerationInspired by the microscopic architecture of natural cartilage,we engineered a novel double-network hydrogel with interconnected polymer-supramolecular polymer double-network?PS-DN gel?for cartilage regeneration.The polymer network is made of polyacrylamide and the supramolecular polymer network comprises of a kind of self-assembled peptide fibers.Upon mechanical loading,the peptide fibers serve as sacrificial bonds to efficiently dissipate energy.They can quickly reform when mechanical load is released thanks to the fast and accurate peptide self-assembly.These entail the PS-DN gel of high mechanical strength of?0.32-0.57 MPa,fracture energy of?300-2670 J m^-2,compressibility of?66%-90%,and fast recovery in seconds.The gel also shows significant energy dissipation,strain stiffening,and stress relaxation behaviors similar to articular cartilage.Moreover,the mechanical properties of the PS-DN gel can be tailored by adjusting the chemical components of the gel.Therefore,this novel biomaterial represents a promising candidate for the regeneration of cartilage and other load bearing tissues.?2?Strong dual-crosslinked hydrogels for ultrasound-triggered drug deliveryHydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems?DDS?.However,it remains challenging to engineer hydrogels that specifically respond to externally applied mechanical forces with minimal basal drug leakage under normal stressful physiological conditions.Here we designed an ultrasound responsive hydrogel-based DDS with special dual-crosslinked nanoscale network architecture.The covalent crosslinks endow the hydrogel high mechanical stability and greatly suppress deformation-triggered drug release.Meanwhile,the dynamic covalent boronate-ester linkages between hydrogel backbone and the anti-inflammation compound,tannic acid?TA?,allow effective ultrasound-triggered pulsatile release of TA.As such,the hydrogel shows distinct drug release profiles under compression and ultrasound.A proof-of-principle demonstration of the suppression of inflammation activation of macrophage upon ultrasound-triggered release of TA was also illustrated.?3?An Injectable Self-Healing Protein HydrogelHydrogels with dynamic mechanical properties are of special interest in the field of tissue engineering and drug delivery.However,it remains challenging to tailor the dynamic mechanical response of hydrogels to simultaneously meet diverse application needs.We synthesized a hetero-coiled-coil complex cross-linked protein hydrogel exhibiting unusual multiple energy dissipation modes and tunable dynamic response.Such unique features confer on the hydrogel responsiveness to mechanical stimuli in a broad range of frequencies.Therefore,the hydrogels are injectable due to their shearing-thinning properties at low shear rates of 0.8 rad s^-1 and can fully recover their mechanical properties within a few seconds due to the intrinsic fast dynamics of the cross-linkers.Moreover,the dynamic response of these hydrogels can be finetuned by the temperature and the hydrogel network structures.These hydrogels are promising candidates for delivering therapeutic drugs,biological molecules,and cells in a broad spectrum of biomedical applications.?4?Molecular engineering of metal-coordination interactions for strong,tough and fast-recovery hydrogelsMany load-bearing tissues,such as muscles and cartilages,show high elasticity,toughness and fast recovery.However,combining these mechanical properties in the same synthetic biomaterials?i.e.hydrogels?is fundamentally challenging as they require contradictive mechanical and dynamical properties of the cross-linkers.For example,hydrogels cross-linked by stable bonds are strong but recover slowly and hydrogels cross-linked by dynamic bonds recover quickly but are mechanically weak.In this part,we show that strong,tough and fast-recovery hydrogels can be engineered using cross-linkers involving cooperative dynamic interactions.We designed a histidine-rich decapeptide containing tandem repeats of two zinc binding motifs.This decapeptide had a stronger binding strength,higher thermodynamic stability,and faster binding rate than single binding motif or isolated ligands?histidine?.The engineered hybrid network hydrogels containing the peptide-metal complex exhibit a high elasticity of?220 k Pa,ultra-toughness of?4,030 k J m^-3 and fast recovery in seconds under multiple load-unload cycles,comparable to mechanical properties of articular cartilage.We expect that they can function effectively as scaffolds for load-bearing tissue engineering and as building blocks for soft robotics.Our results provide a general route to tune the mechanical and dynamic properties of hydrogels at the molecular level.