Preparation And Performance Of Functional Bone Adhesive Hydrogel

Fractures,as the most common bone tissue trauma,seriously threaten the health of tens of millions of people.In particular,comminuted fractures bring critical challenge to surgical treatment,which can easily lead to malalignment of fractures and eventually result in complications such as nonunion.Bone adhesive has received widespread attention due to its fast and stable bone adhesion performance,providing a new feasibility solution for fracture treatment.However,Severe deficiencies,including poor biocompatibility and degradability,remain in current products,which result in high failure rates for bone healing.Adhesive hydrogels are widely used in research in the fields of tissue hemostasis and tissue bonding due to their excellent tissue bonding performance,biocompatibility and degradability.In addition,by simulating the characteristics of bone tissue or extracellular matrix,hydrogel adhesives can be given excellent biological performance,such as antibacterial property,promote cell proliferation and eliminate inflammation.However,integration of bone tissue adhesion and long-term biological properties in one adhesive hydrogel is often ignored.In view of this,it is necessary to fabricate an adhesive hydrogel with the property of strong adhesion strength,self-healing and biological function,due to meet the clinical demand.To solve the problem of insufficient adhesion performance of natural polymer base hydrogel adhesive,a novel antibacterial bone adhesive was fabricated after blending the oxidized hyaluronic acid with tannic(TA)and poly-ε-lysine(PL).Due to the electrostatic interaction and dynamic covalent bond,the bone adhesive exhibited prominent adhesion property.250 kPa and 452 kPa in lap-shear and end-to-end adhesion strength was presented,which could meet the different needs of clinical application.The great cytocompatibility of the adhesive could offer an environment suitable for bone tissue healing.Moreover,antibacterial activity of the adhesive that provide by TA could decreased the risk of bacterial infection at the site of fracture.In order to endow adhesive hydrogel with osteogenic properties,on the basis of work 1,a strategy to construct hybrid adhesive hydrogel with host tissue adhesive properties,enhanced mechanical strength and osteogenic effects was developed.Simvastatin(SIM)was firstly incorporated into zeolitic imidazolate framework-8(ZIF8)and surface decoration with hydroxyapatite was realized to obtain SIM loaded and hydroxyapatite modified ZIF-8 particles(DHZS).As the inorganic strengthening component,DHZS could further cross-link the mixture of dopamine-hyaluronic acid(dHA)and tannic(TA)via coordination interaction and hybrid adhesive hydrogel(dHA/TA/DHZS)was fabricated.Sufficient phenolic groups endowed dHA/TA/DHZS with excellent defect filling ability and tissue adhesion,while incorporation of DHZS significantly improved the mechanical strength and stability of hydrogel.Due to the multiple protective effects of ZIF-8 and hydrogel,SIM was sustainably released from dHA/TA/DHZS.Together with the active Zn2+and Ca2+,they upregulated the expressions of ALP,OCN and Runx2,and promoted mineralization as well.Together with the antibacterial effect,this adhesive hydrogel holds great potential for bone defects repair.