Animal Experimental Study On Prevention Of Implant-related Infection By 3D Printing Porous Titanium Combined With Local Mineralized Sustained-release Hydrogel Coating

Objective:In orthopaedics,the use of internal fixation implants due to a variety of fractures,joint replacement and other reasons will cause implant-related infections,often resulting in serious consequences.The incidence of implant-related infections is usually very low,ranging from 0.3%to 3%.However,once diagnosed,the impact on patients is enormous.Biofilm-associated infection becomes a medical and surgical challenge by destroying adjacent tissues,resulting in poor angiogenesis,implant loosening,shedding and even dislocation.Patients are forced to undergo multiple invasive surgery,resulting in functional defects of the affected limbs and increasing the expenditure of national medical and health resources.At present,the most common clinical solutions include debridement combined with systemic antibiotics,but the effect is mediocre.Antibiotic sustained release coating has gradually become a research hotspot.In order to combine bone growth and antibacterial function,we used rabbit implant-related osteomyelitis model,3D printed porous titanium metal was implanted into bilateral tibial metaphysis of rabbits,and the effect of chitosan/gentamicin/calcium carbonate（CSMA/GEN/Ca CO₃）composite hydrogel coating on preventing implant-related infection in vivo was analyzed.Methods:20 adult New Zealand white rabbits were randomly divided into 4 groups（n=5 in each group）:empty titanium group,CSMA coating group,CSMA/Ca CO₃coating group and CSMA/GEN/Ca CO₃coating group.Then the experimental results were evaluated by clinical symptoms,imaging examination and histopathology of local or systemic infection.Results:（1）The inflammatory indexes of each group were judged by measuring the rectal temperature of rabbits.The trend of body temperature in CSMA group was basically the same as that in CSMA/Ca CO₃group:rectal temperature increased at first from the first week,decreased slightly in the second week,and decreased significantly to the normal level after 4 weeks.The rectal temperature in the CSMA/GEN/Ca CO₃group decreased from 39.8℃to 39.1℃2 weeks after operation and returned to normal in the 4th week.The body temperature in the empty titanium group was the highest at all time points,and even did not return to the normal range after 4 weeks.（2）The redness,swelling and exudation around the wound in the CSMA/GEN/Ca CO₃group and the empty titanium group were recorded at an interval of two consecutive days.The results showed that the infection around the incision was aggravated and the wound was red and swollen with purulent secretion in the empty titanium group 6 days after operation.Perfect bacteriological culture suggested Staphylococcus aureus infection,while in the CSMA/GEN/Ca CO₃group,there was slight swelling around the skin,but there was no peri-skin exudation and abscess formation.It was observed for several days that hair began to grow around the incision.（3）Four weeks after modeling,X-ray showed that there were typical symptoms of chronic osteomyelitis in the empty titanium group,including periosteal reaction,local hyperosteogeny and sclerosis,Norden score 3,mild periosteal reaction and surrounding soft tissue swelling in CSMA group and CSMA/Ca CO₃group,Norden score 1,CSMA/GEN/Ca CO₃group no obvious abnormality,Norden score 0.（4）the qualitative and quantitative results of Micro-CT,HE staining and Goldner’s trichrome staining of hard tissue sections in CSMA/GEN/Ca CO₃coating group showed better osteogenic ability.Conclusion:（1）The CSMA/GEN/Ca CO₃composite hydrogel coating was successfully constructed in this study,which has the characteristics of UV correspondence and injectability,and the method of CO₂diffusion in situ mineralization is suitable for changing the internal pore structure of titanium implants.（2）Through the study in rabbits,CSMA/GEN/Ca CO₃composite hydrogel coating showed superior antibacterial effect and osteogenic ability.（3）The porous titanium implant coating has the advantages of synergistic antibacterial,osteogenesis,good cytocompatibility and simple operation,which provides a simple and effective scheme for clinical prevention and treatment of implant-related infection.