| Anterior cruciate ligament(ACL)tear is the most common sports injury.At present,the most effective treatment for ACL injury currently is ACL reconstruction.Although the surgical success rate is high,the postoperative ligament laxity and re-fracture may occur.The autologous hamstring tendon,HT,has become one of the most commonly used implants due to its advantages such as fewer complications at the site where the tendon is taken.But the tendon as the implant has two problems.On the one hand,the tendon done between the tendon and the bone tunnel is very difficult to heal.It is reported in the literature that KGN has a strong and specific effect in promoting the differentiation of mesenchymal stem cells into chondrocytes,and can accelerate bone regeneration.However,due to the short action time and poor effect of its direct injection administration,a KGN sustained-release system is necessary to exert its efficacy.It is reported in the literature that Kartogenin(KGN)combined with PRP gel can achieve the purpose of sustained release of KGN and can significantly promote the regeneration of fibrocartilage at the tendon bone interface of the rotator cuff and the Achilles tendon which can promote tendon-bone healing,but there is no relevant study on its therapeutic effect on tendon-bone healing after ACL reconstruction.On the other hand,using HT as the implant,the tendon will creep after ACL reconstruction and the mechanical properties will be greatly reduced,and this process may take up to 2 to 4 years.The implant needs to maintain a constant tension during this period to ensure a successful ACL reconstruction.The suture augmentation is used as an internal bracket during the surgery to protect the reconstructed ACL,and it has been used in clinical practice,but the treatment effect is not consistent.Moreover,there is no relevant study on whether there is stress shielding which affects the maturity of the transplanted tendon.In this study,the work is carried out from 2 aspects,in the first part,it clarifies whether KGN-PRP gel can play a role in promoting tendon bone healing after ACL reconstruction,and further to explore its potential mechanism in promoting tendon-bone healing.In the second part,the retrospective study investigates whether the suture augmentation technique can protect the reconstructed ACL from its injury and improve the postoperative clinical efficacy,and whether the suture augmentation affects the transplanted tendon maturity is analyzed through the postoperative nuclear magnetic observation.Part One Kartogenin combined PRP promoted tendon-bone healing or anterior cruciate ligament reconstruction by suppressing inflammatory response via targeting AKT/PI3K/NF-κBObjective: the aim of this study was to investigate whether KGN-PRP gel injection in ACL reconstructed bone tunnels could effectively promote tendon-bone healing,and the potential mechanism was further researched.Method: Kartogenin was dissolved in dimethyl sulfoxide and then diluted into PRP solution liquid to prepare KGN-PRP gel.HPLC was used to measured release rate of KGN from KGN-PRP gel.Except the sham group,an ACL injury reconstruction model in rabbits was established and the rabbits received saline,PRP and KGN-PRP injection onto the tendon-bone interface after reconstruction.The tissue was harvested from the tendon-bone interface at 4 weeks and 8 weeks post-surgery,and the sections were stained with Safranin O/fast green to detected tendon-bone healing.Immunochemistry staining was used to analyzed the VEGF,Collagen I and HIF-1α expression and ELISA assay was used for detecting inflammatory factors such as IL-6,TNF-α and COX-2 concentrations.The expression level of AKT/PI3K/NF-κB related protein and m RNA were presented by Western blot and q PCR.Result: KGN in vitro release experiments showed a high KGN release rate within 4 d,followed by continuous release for 7 d in KGN-PRP gels.Safranin O/fast green staining results showed that the KGN+PRP group had more positive tissue color at the tendon bone interface and produced more cartilage tissue compared to the model and PRP groups.Biomechanical test results showed that the maximum damage load and stiffness at the tendon bone junction were significantly higher in the KGN-PRP group than in the PRP group.the expression of type I collagen,VEGF and HIF-1α in the regenerated tissue at the tendon bone interface was significantly higher in the KGN-PRP group than in the PRP group and the model group.The expression of inflammatory factors such as IL-6,TNF-α and COX-2 at the tendon bone interface were most significantly reduced in the KGN-PRP group compared with the model and PRP groups.WB and q PCR results showed that the KGN-PRP group inhibited the activation of AKT/PI3K/NF-κB inflammatory pathway more significantly compared with the PRP group,thereby reducing the level of inflammation and promoting tendon bone healing.Summary: PRP is an effective carrier for KGN with the sustained release of KGN.After ACL reconstruction,injection of KGN-PRP gel significantly reduced the inflammatory response and inhibited AKT/PI3K/ NF-κB activation in cartilage tissue,promoted tendon-bone healing.Part two Effect of suture augmentation technique on short-term clinical efficacy of reconstruction of the anterior cruciate ligament with the autologous hamstring tendon and the maturity of the implanted tendonObjective: To investigate the short-term clinical efficacy of the suture augmentation technique on ACL reconstruction by autologous HT,and to evaluate whether the suture augmentation affects the maturity of the transplanted tendon by MRI examination.Method: This study is a retrospective study of clinical and imaging data of patients,and the clinical and imaging data of patients undergoing ACL reconstruction in our hospital from January 2018 to January 2021 have been reviewed.The cases were screened according to inclusion criteria and exclusion criteria and divided into suture augmentation(SA)group and without suture augmentation(WSA)group according to whether the suture augmentation was used during the surgery.Eighty-seven subjects were included in the study,and 47 subjects were followed up,with the follow-up rate of 54.0%.27 men and 20 women were included;the mean age was 27.2 ± 3.5 years,and the mean follow-up time was 14 months.Of these,22 patients were included in the SA group and 25 patients were included in the WSA group.There were no significant differences in age,gender composition,combined injury,time from injury to surgery,as well as the follow-up time.The subjective and objective evaluation were made at the last postoperative follow-up in the two groups,including Tegner Activity Score(TAS),the Marx Activity Rating Scale(MARS),the Lysholm knee score scale(LKSS),the Knee Injury and Osteoarthritis Outcome Score(KOOS),and the objective evaluation included knee physical examination and signal/noise quotient(SNQ)of the implants.The results of subjective and objective evaluation were compared with SPSS 22.0 statistical software,and P<0.05 was used as the statistical difference criterion.Result: There were no significant differences in each score of LKSS,KOOS-pain,KOOS-symptoms,KOOS-ability for activity of daily living,KOOS-Sports-entertainment ability,KOOS-knee-related quality of life.The Marx activity rating was 11.1±1.9 in the SA group and 9.8 ± 2.2 in the WSA group,with a significant difference(P<0.05).Tegner Motor score was 5.7 ± 1.0 in the SA group and 5.0 ± 1.0 in the WSA group,which was statistically significant(P<0.05).There was no significant difference in the scores of joint effusion,limited knee extension,limited knee flexion,lachman test,anterior drawer test,pivot shift test and overall evaluation.The difference between the anterior tibial shift in the SA group was 1.5±0.5,and the anterior tibial shift was 1.6±0.5 in the WSA group.There was no significant difference between the two groups(P=0.793).The proximal SNQ of the implant was 17.1±2.9 in the SA group and the proximal SNQ of the implant was 18.2±3.5 in the WSA group.There was no significant difference between the two groups(P=0.470).The intermediate section SNQ of the implant was 15.0±3.8 in the SA group,and the intermediate section SNQ of the implant was 16.1±4.3 in the WSA group.There was no significant difference between the two groups(P=0.349).The distal SNQ of the implant was 16.5±5.6 in SA group and the distal SNQ of the implant was 15.7±4.3 in WSA group.There was no significant difference between the two groups(P=0.072).Summary: The suture augmentation technique improved the short-term clinical effect of ACL reconstruction and had no significant effect on the maturity of the implante tendon.Conclusions: PRP is an effective carrier for KGN with the sustained release of KGN.After ACL reconstruction,injection of KGN-PRP gel significantly reduced the inflammatory response and inhibited AKT/PI3K/ NF-κB activation in cartilage tissue,promoted tendon-bone healing.The suture augmentation technique improved the short-term clinical effect of ACL reconstruction and had no significant effect on the maturity of the implante tendon. |
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