Study On Melt Electrohydrodynamic 3D Printed Drug-loaded Scaffolds For Anti-infection In Bone Repair

Implanted scaffold or bone substitute is a common method to treat bone defects.Among them,biomaterial implants have attracted more and more researchers’ attention in the treatment of bone defects.However,during bone trauma surgery,implant-related bone infections such as osteomyelitis often occur,which impedes bone repair and has been a challenging clinical problem.Antibiotics are the most common clinical precaution and treatment for bone infections.However the traditional oral and systemic antibiotic treatment may be ineffective,because biofilms are easily formed on the bone surface,which increases the resistance of bacteria.Moreover,because antibiotics are difficult to reach the site of infection and high concentrations of antibiotics can cause nephrotoxicity and liver toxicity,which also limits the total amount of antibiotics.Local antibiotic treatment has been proved to improve the bioavailability of drug and reduce the side effects of frequent medication.Melt electrohydrodynamic(EHD)3D printing is an emerging micronanofber manufacturing technology,by which fibers could be precisely deposited in pre-defned patterns,and it has been widely applied to fabricate bioscaffolds for tissue engineering,especially in bone repair.Therefore,in order to solve the problem of local anti-infection in bone repair,in this thesis,poly(ε-caprolactone)(PCL)/polyethylene glycol(PEG)/roxithromycin(ROX)composite scaffold was prepared via melt EHD 3D printing technology with ROX as a model drug and PCL and PEG as carriers.The following are the main research contents of this article:First,a melt electrohydrodynamic 3D printing equipment was designed and developed according to the experimental requirements.Then PCL/PEG/ROX composite scaffolds with different ratios were printed by adjusting the process parameters of the equipment.Then the physical and chemical characterization of the composite scaffold were performed,including the use of scanning electron microscopy to characterize the fiber morphology,the use of Fourier infrared spectroscopy to characterize the fiber composition,and the use of water contact angle equipment to characterize the hydrophilicity of the fibrous scaffold.The experimental results showed that the PCL/PEG/ROX composite scaffold with 5%PEG content had good morphology,and PEG and ROX were successfully loaded into the PCL scaffold.The water contact angle results showed that both ROX and PEG could increase the hydrophilicity of PCL scaffold and PEG has a greater effect on the hydrophilicity of the scaffold.Then the drug release of the composite scaffold in vitro was measured.The experimental results showed that the short-term burst release and subsequent long-term sustained release behavior of the antibiotic in the melt EHD printed scaffold makes it a very promising system as anti-infective implants in bone repair.Moreover,the addition of PEG can increase the drug release rate.Then three drug delivery models were used to fit the experimental data,and the results showed that the first-order equation fitting results were consistent with the experimental results.Then the antibacterial treatment effect of the composite scaffold againt E.coli and S.aureus were determined by respectively using the disc diffusion assay and dynamic contact assay.The experimental results showed that the composite scaffold had a spectral antibacterial effect,especially for S.aureus,which are the main bacteria in bone infection,and the addition of PEG increased the bacteriostatic effect of the composite scaffold.Finally,the effects of composite scaffolds on cell morphology and toxicity were determined by using immunostaining and MTT assay.The experimental results showed that the PCL/PEG/ROX scaffold had high biocompatibility.The hydrophilic properties of the scaffold can effect the adhesion and proliferation of cells,and the composite scaffold with 5%PEG content showed the best cell adhesion and proliferation.All this indicated that the PCL/PEG/ROX composite scaffold made by melt EHD 3D printing could be a potential anti-infective implant for bone repair.