Comparison Of The Efficacy Of OWHTO And Combined Autologous Adipose Mesenchymal Stem Cell Injection In The Treatment Of Early Inversion Knee Osteoarthritis

Background:Knee osteoarthritis(KOA),one of the most common chronic joint diseases,is characterised by a progressive deterioration of the knee cartilage,a deterioration that often leads to pain,stiffness and reduced mobility.The incidence of this disease has been on the rise in our country,with a significant impact on the quality of life of patients and a huge social and economic burden.For early osteoarthritis of the knee with inversion deformity,open wedge high tibial osteotomy(OWHTO)has been shown to be a viable treatment option.This procedure involves osteotomy of the upper part of the tibia,shifting the line of force from the affected medial compartment to the relatively healthier lateral compartment,relieving the pressure on the medial side,providing pain relief for patients suffering from osteoarthritis of the knee.It is a "knee preservation" procedure in the traditional sense,as it maintains the integrity of the patient’s original knee joint,thus optimising their motion and providing greater comfort than joint replacement surgery.Many studies have shown that OWHTO significantly improves knee function scores,reduces pain and restores joint function.With advances in preoperative planning and surgical techniques and the improvement of internal fixation devices,the incidence of complications is decreasing and the efficacy of OWHTO is increasingly recognised,but its effectiveness in repairing cartilage remains controversial.Mesenchymal stem cells(MSCs)have the ability to self-renew and differentiate into multiple cell lines,and are found in large numbers in a variety of tissues throughout the body.Their inherent ease of isolation,extensive expansion and versatile differentiation have generated a wave of optimism in the treatment of diseases that have limited response to conventional drug interventions.As a result,MSCs have become the focus of research in the field of tissue regenerative medicine,igniting hope and exploring new avenues for the development of new therapeutic approaches.maumus et al.found that MSCs could slow the progression of osteoarthritis and promote cartilage regeneration by affecting the expression of relevant enzymatic factors within the joint microenvironment.MSCs are available from a variety of sources,including spinal cord tissue,human umbilical cord blood,Adipose tissue,etc.Autologous adipose-mesenchymal derived stem cells(ADMSCs)are ideal seed cells because of their low immunogenicity,low rejection,high expansion capacity and ease of procurement compared to other sources.A combination therapy involving high tibial osteotomy(HTO)and MSCs has been studied in the literature for the treatment of osteoarthritis of the knee.Koh et al.used adipose MSCs in combination with HTO to treat osteoarthritis of the knee.However,few studies have been reported on the efficacy of OWHTO combined with autologous adipose MSCs versus OWHTO alone in the treatment of knee cartilage injuries,and most of them were retrospective studies with a surgical and concurrent arthroscopic stem cell implantation design.In this study,a prospective randomised study design was used.Considering that intraoperative arthroscopic stem cell implantation during high tibial osteotomy may affect the outcome due to irrigation,bleeding and early postoperative mobility,a combination of intra-articular injection of MSCs one month after surgery was used to assess the status of knee cartilage regeneration and functional improvement using phase Ⅱ MRI,phase Ⅱ arthroscopy and knee function scale scores.Functional improvement.Objective:The aim of this study was to analyse the clinical outcome of open wedge tibial high osteotomy combined with intra-articular injection of autologous adipose-derived mesenchymal stem cells one month postoperatively in the treatment of early inversion knee osteoarthritis,the results of phase Ⅱ MRI and phase II arthroscopic exploration and to compare them with the results of OWHTO alone.This is in anticipation of guiding recommendations for the use of OWHTO in combination with ADMSCs.Materials and methods:A prospective randomized controlled study design was used to indude patients who were clearly diagnosed with osteoarthritis of the knee according to the Diagnostic Criteria for Osteoarthritis at the same hospital and were randomized into two groups,patients treated with OWHTO surgery only(OWHTO group)and patients treated with OWHTO combined with one month postoperative autologous adipose mesenchymal stem cell intra-articular knee injection(OWHTO+ADMSCs group).In both groups,general demographic information and intraoperative support angle,intraoperative bracing height,operative time,days in hospital,and Kellgren-Lawrence classification of knee osteoarthritis were recorded in detail.Clinical outcomes were assessed in both groups using preoperative and postoperative visual analogue scale(VAS)scores of knee mobility and pain at 6 months and 1 year postoperatively.All patients’ preoperative and 1-year post-operative frontal and lateral radiographs,magnetic resonance imaging(MRI),and two arthroscopic cartilage explorations at the time of internal fixation plate removal were recorded and evaluated by the International Cartilage Repair Society(ICRS)cartilage repair assessment system.The results of the repair were evaluated by the International Cartilage Repair Society Cartilage Repair Assessment System.Result:A total of 45 patients were included,22 in the OWHTO group and 23 in the OWHTO+ADMSCs group.General demographic information and intraoperative support angle,intraoperative bracing height,operative time,postoperative hospital days,and Kellgren-Lawrence classification of knee osteoarthritis were not statistically significant in either group.No complications such as non-healing of the osteotomy surface,delayed healing of the osteotomy surface,incision infection,incision non-healing,implant loosening,implant infection or fracture,lower extremity arterial embolism,or pulmonary embolism occurred in either group during the follow-up period.The radiological results of the two knee X-ray follow-ups before surgery and at the time of removal of the internal fixation plate showed that the alignment of the knee joint improved in both groups relative to the patients’ preoperative conditions(P<0.05),and the final follow-up results of the two groups showed that the intergroup comparison of the hip-knee-ankle angle(HKA),femorotibial angle(FTA),tibial(FTA)and posterior tibial slope(PTS)were not statistically different before and after surgery(P>0.05).In the intra-group comparison between the two groups,VAS scores and knee mobility were significantly improved in each group dining the 1-year follow-up period,with VAS scores decreasing from 4.95±1.84 to 1.91 ± 1.38 preoperatively in the OWHTO group and from 5.00 ± 1.35 to 1.39±1.34 in the OWHTO+ADMSCs group(P<0.01).Comparison of.VAS scores between the two groups(1.91±1.38 in the OWHTO group and 1.39±1.34 in the OWHTO+ADMSCs group,P>0.05)was not statistically significant.Regarding MRI cartilage assessment at the mean(18.33±4.98)months of final follow-up,there was no statistical difference between the two groups for the first MRI cartilage grade comparison(P>0.05)and a statistical difference for the second MRI cartilage grade comparison(P<0.05).For arthroscopic cartilage assessment,there was no statistical difference in the first arthroscopic cartilage grade comparison between the two groups(P>0.05),and the second arthroscopic cartilage grade comparison between the OWHTO group:4 cases of grade Ⅰ,7 cases of grade Ⅱ,6 cases of grade Ⅲ,and 5 cases of grade Ⅳ;and the OWHTO+ADMSCs group:10 cases of grade Ⅰ,9 cases of grade Ⅱ,3 cases of grade Ⅲ,and 1 case of grade Ⅳ,with statistical differences(P<0.05).Conclusion:This study showed that clinical outcomes such as clinical scores and knee mobility improved significantly in both groups compared to the pre-operative period.However,there were no significant differences in clinical scores and knee mobility between the two groups during the short-term follow-up period(one year).Although there were no statistical differences in clinical scores between the two groups at one year,the OWHTO+ADMSCs group had better clinical scores and mobility scores than the OWHTO group overall,and their long-term clinical outcomes(beyond one year)will need to be investigated during long-term follow-up.In addition,patients in both the OWHTO+ADMSCs and OWHTO groups showed a significant improvement in cartilage repair at the second MRI examination and at the second arthroscopic procedure compared to the preoperative period,and there was a statistically significant difference between the two groups.Thus,in the treatment of early inversion knee osteoarthritis,the combination of OWHTO with intra-articular injection of ADMSCs one month after surgery was more effective in cartilage regeneration compared to OWHTO surgery alone according to the second MRI and second arthroscopic cartilage repair grading.Furthermore,both patient groups demonstrated good clinical outcomes in the short term,with no significant complications occurring during this period.We therefore conclude that a single intra-articular injection of autologous adipose-derived stem cells one month postoperatively is a safe and effective procedure to accompany OWHTO in the treatment of cartilage damage in early osteoarthritis of the knee.