| Background:Periprosthetic joint infection(PJI)after unicompartmental knee arthroplasty(UKA)has a low incidence,but once it occurs,it will be a catastrophic complication.Debridement,antibiotics,and implant retention(DAIR)is a routine treatment for acute PJI.Complete removal of all infected and necrotic tissues around the prosthesis is the key to the success of DAIR surgery.The unique feature of PJI after UKA is the presence of natural cartilage.When DAIR is performed in PJI patients after UKA,it is impossible to debride completely,especially the posterolateral and lateral sulcus synovium,because of the small operation space.However,patients with acute PJI after UKA treated by DAIR were as successful as patients with acute PJI after TKA treated by thorough debridement.We hypothesize that there is no or mild infection in the lateral compartment of patients with acute PJI after UKA.There are few studies on PJI in traditional Chinese medicine,and it is classified into"headless gangrene" and "bone carbuncle",which belongs to the category of damp-heat syndrome of warm disease.Conventional damp-heat syndrome model is established by simulating "internal dampness" and "external dampness" combined with low virulence microbial infection to create "guest evil".Clinically,many diseases also show damp-heat syndrome due to infection with highly virulent microorganisms.We put forward the hypothesis that a single high virulence microbial infection can also establish damp-heat syndrome model.To verify the hypothesis,we designed two animal experiments to further explore the histopathological findings of PJI after UKA.Purposes:1.Design of UKA animal prosthesis and establishment of UKA animal model.2.To establish the animal model of PJI after UKA.3.To explore the establishment of the damp-heat syndrome model of a single highly virulent microorganism infection.4.To observe the degree of infection and histopathological changes of synovium and cartilage in the lateral compartment of acute PJI after UKA.Methods:Chapter 1:Beagle dogs(n=4)were selected as experimental subjects,and the lower limb model was restored by three-dimensional reconstruction of normal beagle dogs’ knee joint.The encapsulated 3D model was materialized,and the 3D structure solid model of normal Beagle dog knee joint was established.Eight key parameters of medial compartment of bilateral knee joints were measured.Simulating osteotomy and prosthesis installation,the right knee joint medial femoral condyle prosthesis,tibial plateau prosthesis and plateau liner were designed.Use 3D vertical printer to print medical titanium alloy right knee medial femoral condyle prosthesis and tibial plateau prosthesis,as well as medical ultra-high molecular weight polyethylene plateau liner and osteotomy guide plate.UKA surgery was performed on the right knee joint of beagle dogs.Record the whole body and local conditions of beagle dogs.The range of motion of passive flexion and extension of the right knee joint and the range of motion of the knee joint were measured before operation and at 2,4,12 and 20 weeks after operation.Observe the weight-bearing capacity of right knee joint.X-ray examination of right knee joint was performed immediately and 20 weeks after operation.Chapter 2:Beagle dogs were selected as subjects(n=16)and randomly divided into PJI group(n=12)and control group(n=4).According to the prosthesis designed in Chapter 1,UKA operation on the medial side of right knee joint was completed.In PJI group,methicillin-sensitive Staphylococcus aureus was injected into the right knee cavity immediately after operation at a dose of 5×105 CFU.The control group was injected with normal saline.The experimental period was 3 weeks,and the general situation and local incision of TCM syndrome were observed.Pathogen culture,identification and colony count were carried out on the posterior lateral synovium and lateral cartilage of the prosthesis and lateral compartment.D-lactic acid levels in serum and synovial fluid were detected.The posterior lateral synovium and lateral cartilage of the lateral compartment of the right knee joint were stained with HE Masson and Movat staining to observe the histopathological findings.The expression of Matrix metalloproteinase(MMP)-9 and MMP-13 in the posterolateral synovium and lateral cartilage of the lateral compartment of the right knee joint was detected by immunohistochemical method.Ultrastructural changes of lateral chondrocytes in lateral compartment of right knee joint were observed by transmission electron microscope.GraphPad Prism 9.0 software was used for statistical analysis.Results:Chapter 1:The diameters of anterior condyle and posterior condyle of medial femoral condyle,distal medial condyle,medial tibial plateau and medial tibial plateau were positively correlated with the body weight of the selected Beagle dogs(P<0.05),while the diameters of anterior condyle and posterior condyle of medial femoral condyle were not correlated with the body weight of the selected Beagle dogs(P>0.05).The range of motion of the right knee joint recovered from 99.74 ± 1.470 4 weeks after the operation to 113.55 ±1.27°20 weeks after the operation.There were significant differences between preoperative and postoperative 2 weeks,4 weeks,12 weeks,and 20 weeks(P<0.05).Compared with pre-operation,there were significant differences in weight-bearing scores at 3 days,2 weeks,and 4 weeks after the operation(P<0.05),but no significant differences at 12 weeks and 20 weeks after operation(P>0.05).Imaging evaluation showed that the prosthesis was stable after the operation,and no loosening was found.Chapter 2:All animals survived without signs of systemic disease.From 1 week to 3 weeks after operation,the weight recovery of control group was faster than that of PJI group,with significant difference(P<0.05).There was no significant difference in right thigh circumference and body temperature after operation(P>0.05).In PJI group,no sinus appeared at 1 week,30%of the animals appeared at 2 weeks,and 42%of the animals appeared at 3 weeks.No sinus was formed in the control group,and pathogen culture was negative.In PJI group,the positive rate of pathogen culture was 91.7%,and the positive rate of pathogen culture in lateral cartilage and posterior lateral synovium of lateral compartment was 66.7%.In the PJI group,the colony count of the prosthesis was 195(100.670)× 103 CFU,the colony count of the lateral cartilage of the lateral compartment was 8.5(4,14)× 103 CFU,and the colony count of the posterolateral synovium of the lateral compartment was 6(1,20)X 103 CFU.The colony count between the prosthesis and the lateral cartilage and posterior lateral synovium of the lateral compartment was statistically significant(P<0.05),but the colony count between the lateral cartilage and posterior lateral synovium of the lateral compartment was not statistically significant(P>0.05).In PJI group,the symptoms of damp-heat syndrome,such as lack of energy,lack of movement,decreased appetite,decreased drinking water,yellow urine,irregular stool,sticky smell and filthy taste,incision exudation and poor healing,appeared after modeling.In PJI group,heat was heavier than dampness at 1 week,dampness and heat were equal at 2 weeks,and dampness was heavier than heat at 3 weeks.In the control group,the general condition was good,eating and drinking water were normal,urine color was normal,and stool was formed and non-sticky.The mean concentration of D-lactic acid in synovial fluid of the two groups at 1,2 and 3 weeks after operation was significantly different(P<0.05).The average serum D-lactate concentration in PJI group was higher than that in control group at 3 weeks after operation,and the difference was statistically significant(P<0.05).In PJI group at 1 week,there were single and scattered neutrophil infiltration around blood vessels in posterior lateral synovium of lateral compartment,clear tidal line of lateral cartilage,uneven matrix in superficial layer of cartilage,slight degeneration of chondrocytes and swelling of mitochondrial cristae of chondrocytes.At 2 weeks,the posterior lateral synovium of the lateral compartment showed a large area of inflammatory cell infiltration,tidal drift of cartilage,injury of the lateral cartilage layer and decrease of proteoglycan,obvious swelling,breakage and disappearance of chondrocyte mitochondria,dilation of rough endoplasmic reticulum,infiltration of subchondral bone neutrophils,existence and fibrosis of neutrophils in bone marrow cavity.At 3 weeks,the posterior lateral synovium of the lateral compartment had a large area of inflammatory cell infiltration,the tidal line of the lateral cartilage was layered or interrupted,the cartilage basal substance became shallow,proteoglycan retreated near the tidal line,neutrophils and a large number of lymphocytes were found in the medullary cavity,the deep chondrocytes were degenerated and necrotic,the chondrocytes appeared vacuolar changes,and the number of mitochondria decreased obviously.In the control group,the posterior lateral synovium and lateral cartilage of the lateral compartment were normal in morphology and structure,without neutrophil infiltration,and the cartilage tidal line was clear.Conclusions:1.A canine UKA animal model was established by designing UKA animal prosthesis,which preliminarily proved the safety and stability of UKA animal prosthesis and the reliability of animal model,and recovered the normal motor function of knee joint in a short time.2.A representative animal model of acute PJI after UKA was established,which restored the prosthetic environment of PJI after UKA,and provided the necessary conditions for further study of PJI after UKA.3.It is proved that the single high virulence Staphylococcus aureus infection can also establish the damp-heat syndrome model of infectious diseases,and the establishment method of the damp-heat syndrome model is improved.4.Based on the pathological changes,the best time window of DAIR treatment for patients with acute PJI after UKA is within 1 week,which provides a theoretical basis for DAIR treatment for patients with acute PJI after UKA. |
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