Application Of Mussel-inspired Magnetic Hydroxyapatite Incorprated Gelatin Hydrogel For Bone Repair

To promote the bone healing efficiency,it is necessary to design bone repair materials according to the special physiological environment of bone defects.The use of non-invasive physical signals and biochemical signals is a common strategy to promote bone tissue repair.Magnetic stimulation has been widely used in tissue regeneration and repair.The magnetic responsive hydrogels prepared by combining magnetic responsive nanomaterials and hydrogel matrix can effectively response to external magnetic stimulation and thus benefit tissue repair.Gelatin-based hydrogels with excellent cell affinity can provide a 3D structure as extracellular matrix,and thus can be employed as substitute materials for filling tissue defects.However,gelatin-based hydrogels have weak mechanical strength,poor thermal stability,and lack of osteoinductivity.Hydroxyapatite is the main inorganic component in the bone tissue with good osteoconductivity.The interaction between magnetic nanoparticles and magnetic field can promote cell proliferation and differentiation.Based on the mussel-inspired chemistry,this study developed a new type of magnetic responsive gelatin-based nanocomposite hydrogels with high mechanical strength and thermal stability for bone defect repair.The main results are as follows:（1）Mussel inspired magnetic hydroxyapatite nanoparticles（PMHA）were prepared by chemical co-deposition method.The morphology,structure and physical properties of the PMHA were characterized.Dopamine was introduced into the synthesizing process due to the reduction ability and metal-chelation effect of catechol group.The particle size and morphology of the nanocomposite can be adjusted to chelate Fe₃O₄ and HA.On the other hand,the introduction of highly reactive catechol groups on the surface of the PMHA nanoparticles can improve the dispersibility of the PMHA nanocomposite in the aqueous solution.（2）Then,a mussel-inspired magnetic gelatin hydrogel was obtained by then incorporating PMHA as nano-reinforcements into a gelatin-based hydrogel.Methacrylic acylated gelatin（Gel MA）,gelatin and polyethylene glycol two glycidyl ether（PEGDE）were used as matrix materials to form gelatin-based chemical crosslinked hydrogels.PMHA were us incorporated into gelatin-based hydrogels,and the mussel-inspired magnetic hydroxyapatite composite gelatin-based hydrogels（PMHA-G-GMA）were prepared.The influence of different components on the mechanical properties and thermal stability of the hydrogels were investigated to obtained an optimized hydrogel possessing good mechanical properties,sensitive magnetic response,and excellent thermal stability.（3）Evaluation of biological properties of PMHA-G-GMA hydrogels:Bone marrow stromal cells were cultured on different hydrogels,and the high throughput magnetic field device were used to provide magnetic stimulation.The cell proliferation and differentiation on different hydrogels under magnetic stimulation were investigated.The results showed that the PMHA-G-GMA hydrogels and static magnetic field had synergetic effect on cell proliferation and differentiation,and the optimal intensity of static magnetic field was 10 mt,which was beneficial to cell proliferation and differentiation.Furthermore,PMHA-G-GMA combined with static magnetic field promoted bone repair in vivo.In summary,this study proposed mussel-inspired strategy to develop magnetic hydroxyapatite nanoparticles and manganic gelatin-based hydrogels.The hydrogels showed strong mechanical strength,excellent magnetic responsiveness,high thermal stability,and good cell affinity.Most importantly,the hydrogels can respond to external magnetic field to regulate cell differentiation and promote bone defect repair.