Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial) The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee Does Intra Articular Platelet Rich Plasma Injection Improve Function, Pain and Quality of Life in Patients with Osteoarthritis of the Knee? A Randomized Clinical Trial Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Comparison Between Hyaluronic Acid and Platelet-Rich Plasma, Intra-articular Infiltration in the Treatment of Gonarthrosis Effect of single injection of platelet-rich plasma in comparison with corticosteroid on knee osteoarthritis: a double-blind randomized clinical trial. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032. Does intraoperative application of leukocyte-poor platelet-rich plasma during arthroscopy for knee degeneration affect postoperative pain, function and quality of life? A 12-month randomized controlled double-blind trial Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions Treatment of Knee Joint Osteoarthritis with Autologous Platelet-Rich Plasma in Comparison with Hyaluronic Acid Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up. Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis
PURPOSE This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy ( HTO ) for varus deformity , with or without mesenchymal stem cell ( MSC ) therapy .  METHODS This prospect i ve , comparative observational study was design ed to evaluate the effectiveness of MSC therapy . The patients were divided into 2 groups : HTO with platelet-rich plasma ( PRP ) injection only ( n = 23 ) or HTO in conjunction with MSC therapy and PRP injection ( n = 21 ) . Prospect i ve evaluations of both groups were performed using the Lysholm score , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and a visual analog scale ( VAS ) score for pain . Second-look arthroscopy was carried out in all patients at the time of metal removal . RESULTS The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain ( PRP only , 74.0 ± 5.7 ; MSC-PRP , 81.2 ± 6.9 ; P < .001 ) and symptoms ( PRP only , 75.4 ± 8.5 ; MSC-PRP , 82.8 ± 7.2 ; P = .006 ) relative to the PRP-only group . Although the mean Lysholm score was similarly improved in both groups ( PRP only , 80.6 ± 13.5 ; MSC-PRP , 84.7 ± 16.2 ; P = .357 ) , the MSC-PRP group showed a significantly greater improvement in the VAS pain score  ( PRP only , 16.2 ± 4.6 ; MSC-PRP , 10.2 ± 5.7 ; P < .001 ) . There were no differences in the preoperative ( PRP only , varus 2.8 ° ± 1.7 ° ; MSC-PRP , varus 3.4 ° ± 3.0 ° ; P = .719 ) and postoperative ( PRP only , valgus 9.8 ° ± 2.4 ° ; MSC-PRP , valgus 8.7 ° ± 2.3 ° ; P = .678 ) femorotibial angles or weight-bearing lines between the groups . Arthroscopic evaluation , at plate removal , showed that partial or even fibrocartilage coverage was achieved in 50 % of the MSC-PRP group patients but in only 10 % of the patients in the PRP-only group ( P < .001 ) . CONCLUSIONS MSC therapy , in conjunction with HTO , mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Introduction Knee osteoarthritis ( OA ) is the most common articular disease . Different methods are used to alleviate the symptoms of patients with knee OA , including analgesics , physical therapy , exercise prescription , and intra-articular injections ( glucocorticoids , hyaluronic acid [ HA ] , etc ) . New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage , including the use of platelet-rich plasma ( PRP ) as a complex of growth factors . Due to the high incidence of OA and its consequences , we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA . Method This non-placebo-controlled r and omized clinical trial involved 160 patients affected by knee OA , grade 1–4 of Kellgren – Lawrence scale . In the PRP group ( n = 87 ) , two intra-articular injections at 4-week interval were applied , and in the HA group ( n = 73 ) , three doses of intra-articular injection at 1-week interval were applied . All patients were prospect ively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) and SF-36 question naires . The results were analyzed using SPSS 16.1 software ( RCT code : I RCT 2014012113442N5 ) . Results At the 12-month follow-up , WOMAC pain score and bodily pain significantly improved in both groups ; however , better results were determined in the PRP group compared to the HA group ( P < 0.001 ) . Other WOMAC and SF-36 parameters improved only in the PRP group . More improvement ( but not statistically significant ) was achieved in patients with grade 2 OA in both the groups . Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment Purpose To assess the outcome of intra-articular platelet-rich plasma ( PRP ) injections into the knee in patients with early stages of osteoarthritis ( OA ) and to determine whether cyclical dosing would affect the end result . Methods This is a prospect i ve , r and omized study in which 93 patients ( 119 knees ) were followed up for a minimum of 2 years . Fifty knees were r and omly selected prior to the first injection , to receive a second cycle at the completion of 1 year . A cycle consisted of three injections , each given at a monthly interval . The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , Visual Analogue Scale ( VAS ) , Tegner and Marx scoring systems , recorded prior to the first injection and then at 12 , 18 and 24 months . Results There was a significant improvement in all scores over time compared to the pre-treatment value ( p < 0.001 ) . At 12 months , both groups showed similar and significant improvement . At 18 months , except for KOOS ( Symptoms ) and Tegner score , all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle ( p < 0.001 ) . At 2 years , the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores . Conclusion Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option . There is a significant reduction in pain and improvement in function after 12 months , which can be further improved at 18 months by annual repetition of the treatment . Although the beneficial effects are ill sustained at 2 years , the results are encouraging when compared to the pre-treatment function . Level of evidence II We design ed a r and omized clinical trial with control group , to investigate the effects of platelet rich plasma ( PRP ) on pain , stiffness , function and quality of life in patients with knee osteoarthritis . Patients were r and omly divided in two groups . For both groups of participants , therapeutic exercise was prescribed . In the PRP group , two courses of leukocyte rich PRP ( 5.6 fold higher platelet concentration ) with a 4-week interval was injected . For each participant , Western Ontario and McMaster University ’s Arthritis Index ( WOMAC ) and the SF-36 question naire ( Farsi version ) were filled at the baseline and 6 months after treatments . Thirty-one patients in the PRP group and 31 patients in the control group were studied .  Mean changes of total WOMAC , physical component summery and mental component summery of Short Form-36 in PRP group showed better improvement than control group ( P<0.05 ) . This study showed that intra articular PRP knee injection combined with therapeutic exercise can be more effective in pain reduction and improvement of stiffness and quality of life , compared with therapeutic exercise alone Purpose This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis ( OA ) given an intra-articular injection of platelet-rich plasma ( PRP ) , hyaluronic acid ( HA ) or ozone gas . Methods A total of 102 patients with mild – moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were r and omly separated into three groups . Group 1 ( PRP group ) received intra-articular injection of PRP × 2 doses , Group 2 ( HA group ) received a single dose of HA , and Group 3 ( Ozone group ) received ozone × four doses . Weight-bearing anteroposterior – lateral and Merchant ’s radiographs of both knees were evaluated . WOMAC and VAS scores were applied to all patients on first presentation and at 1 , 3 , 6 and 12 months . Results At the end of the 1st month after injection , significant improvements were seen in all groups . In the 3rd month , the improvements in WOMAC and VAS scores were similar in Groups 1 and 2 , while those in Group 3 were lower ( p < 0.001 ) . At the 6th month , while the clinical efficacies  of PRP and HA were similar and continued , the clinical effect of ozone had disappeared ( p < 0.001 ) . At the end of the 12th month , PRP was determined to be both statistically and clinical ly superior to HA ( p < 0.001 ) . Conclusion In the treatment of mild – moderate knee OA , PRP was more successful than HA and ozone injections , as the application alone was sufficient to provide at least 12 months of pain-free daily living activities . Level of evidence Therapeutic study , Level UNLABELLED : Osteoarthritis ( OA ) is the most widespread musculoskeletal disorder in adults . It leads to cartilage damage associated with subchondral bone changes and synovial inflammation , causing pain and disability . The present study aim ed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells ( ASCs ) in patients with knee OA , as well as clinical efficacy as secondary endpoint . A bicentric , uncontrolled , open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries . From April 2012 to December 2013 , 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs . The study design consisted of three consecutive cohorts ( six patients each ) with dose escalation : low dose ( 2 × 10(6 ) cells ) , medium dose ( 10 × 10(6 ) ) , and high dose ( 50 × 10(6 ) ) . The primary outcome parameter was safety evaluated by recording adverse events throughout the trial , and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index . After 6 months of follow-up , the procedure was found to be safe , and no serious adverse events were reported . Four patients experienced transient knee joint pain and swelling after local injection . Interestingly , patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline . Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients . A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy . SIGNIFICANCE Although this phase I study included a limited number of patients without a placebo arm , it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis . This study also provides encouraging preliminary evidence of efficacy . Larger and controlled long-term studies are now m and atory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis Mesenchymal stem cells ( MSCs ) are known to have a potential for articular cartilage regeneration . However , most studies focused on focal cartilage defect through surgical implantation . For the treatment of generalized cartilage loss in osteoarthritis , an alternative delivery strategy would be more appropriate . The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs ( AD-MSCs ) for knee osteoarthritis  . We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee . The phase I study consists of three dose-escalation cohorts ; the low-dose ( 1.0 × 10(7 ) cells ) , mid-dose ( 5.0 × 10(7 ) ) , and high-dose ( 1.0 × 10(8 ) ) group with three patients each . The phase II included nine patients receiving the high-dose . The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index ( WOMAC ) at 6 months . Secondary outcomes included clinical , radiological , arthroscopic , and histological evaluations . There was no treatment-related adverse event . The WOMAC score improved at 6 months after injection in the high-dose group . The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group . Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group . Histology demonstrated thick , hyaline-like cartilage regeneration . These results showed that intra-articular injection of 1.0 × 10(8 ) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events , and reduced cartilage defects by regeneration of hyaline-like articular cartilage Background : Arthrosis is particularly prevalent in the knee . Infiltration treatment for gonarthrosis is among the most widely used techniques in orthopaedic practice . Purpose : To compare the clinical response of hyaluronic acid ( HA ) and platelet-rich plasma ( PRP ) treatment in 2 groups of patients affected by gonarthrosis . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 120 patients affected by clinical ly and radiographically documented gonarthrosis were included in this study . The gonarthrosis was grade d using the Kellgren-Lawrence radiographic classification scale . The 120 patients were r and omized into 2 study groups in a 1:1 ratio : 60 patients received 4 intra-articular injections of PRP ( specifically , autologous conditioned plasma [ ACP ] , 5.5 mL ) , and 60 patients received 4 intra-articular injections of HA ( 20 mg/2 mL ) . An unblinded physician performed infiltration once a week for 4 weeks into the knee affected by clinical ly relevant gonarthrosis ( in both groups ) . All patients were evaluated with the Western Ontario and McMaster ( WOMAC ) score before the infiltration and at 4 , 12 , and 24 weeks after the first injection . Results : Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuously improving sustained effect up to 24 weeks ( WOMAC score , 65.1 and 36.5 in the HA and ACP groups , respectively ; P < .001 ) , where the clinical outcomes were better compared with the results with HA . In the HA group , the worst results were obtained for grade III gonarthrosis , whereas the clinical results obtained in the ACP group did not show any statistically significant difference in terms of the grade of gonarthrosis . The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and 41.20 in the ACP group ( P < .001 ) . Conclusion : Treatment with ACP showed a significantly better clinical outcome than did treatment with HA , with sustained lower WOMAC scores . Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis BACKGROUND Evidence on the effect of platelet-rich plasma ( PRP ) in treating osteoarthritis ( OA ) is insufficient . Therefore , the present study compares the effects of a one-time injection of PRP and corticosteroid ( CS ) . METHODS In the present r and omized double blind clinical trial , the participants who suffered from knee osteoarthritis ( Grade s II/III ) , were r and omly divided into two groups : intra articular injection of PRP and CS .  Knee injury and osteoarthritis outcome score ( KOOS ) , the 20-Meter-Walk Test ( 20MW ) , active and passive ranges of motions ( ROM ) , flexion contracture , and pain intensity based on Visual Analog Scale ( VAS ) were assessed before , 2-months , and 6-months after interventions . RESULTS Forty-one participants ( 48 knees ) were involved in the research ( 66.7 % women ; average age of 61.1±7.0 years old ) . Compared to the group treated with corticosteroid  , pain relief ( df : 6 , 35 ; F=11.0 ; P=0.007 ) , symptom free ( df:6 , 35 ; F=23.0 ; P<0.001 ) , activities of daily living ( ADL ) ( df:6 , 35 ; F=10.7 ; P=0.005 ) and quality of life ( df:6 , 35 ; F=5.2 ; P=0.02 ) in the RPR group were significantly higher , but sporting ability was not different between the two groups ( df : 6 , 35 ; F=0.6 ; P=0.55 ) . PRP was significantly more helpful for relieving patients ' pain ( VAS ) compared to corticosteroids ( df : 6 , 35 ; F=32.0 ; P=0.001 ) . It is also notable that using PRP was more helpful in improving the 20MW test than corticosteroid treatment ( df : 6 , 35 ; F=7.4 ; P=0.04 ) but none of the treatments had any impact on active flexion ROM ، passive flexion ROM and flexion contracture ( P>0.05 ) . CONCLUSIONS Our study demonstrated that one shot of PRP injection , decreased joint pain more and longer-term , alleviated the symptoms , and enhanced the activity of daily living and quality of life in short-term duration in comparison with CS Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of  chronic knee osteoarthritis  that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality Purpose To compare the effectiveness of intraarticular ( IA ) multiple and single platelet-rich plasma ( PRP ) injections as well as hyaluronic acid ( HA ) injections in different stages of osteoarthritis ( OA ) of the knee . Methods A total of 162 patients with different stages of knee OA were r and omly divided into four groups receiving 3 IA doses of PRP , one dose of PRP , one dose of HA or a saline injection ( control ) . Then , each group was subdivided into two groups : early OA ( Kellgren – Lawrence grade 0 with cartilage degeneration or grade I – III ) and advanced OA ( Kellgren – Lawrence grade IV ) . The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale ( EQ-VAS ) and International Knee Documentation Committee ( IKDC ) subjective scores . Adverse events and patient satisfaction were recorded . Results There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group . The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups . There was no significant difference in the scores of patients injected with one dose of PRP or HA . In the early OA subgroups , significantly better clinical results were achieved in the patients treated with three PRP injections , but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups . Conclusion The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA . For patients with early OA , multiple ( 3 ) PRP injections are useful in achieving better clinical results . For patients with advanced OA , multiple injections do not significantly improve the results of patients in any group . Level of evidence OBJECTIVE To estimate the current and future ( to year 2032 ) impact of osteoarthritis ( OA ) health care seeking . METHOD  Population -based study with prospect ively ascertained data from the Skåne Healthcare Register ( SHR ) , Sweden , encompassing more than 15 million person-years of primary and specialist outpatient care and hospitalizations . We studied all Skåne region residents aged ≥45 by the end of 2012 ( n = 531 , 254 ) and determined the prevalence of doctor-diagnosed OA defined as the proportion of the prevalent population that had received a diagnosis of OA of the knee , hip , h and , or other locations except the spine between 1999 and 2012 . We projected consultation prevalence of OA until year 2032 using Statistics Sweden 's ( SCB ) projected age and sex structure and prevalence of overweight and obesity . RESULTS In 2012 the proportion of population aged ≥45 with any doctor-diagnosed OA was 26.6 % ( 95 % confidence interval ( CI ) : 26.5 - 26.8 ) ( men 22.4 % , women 30.5 % ) . The most common locations were knee ( 13.8 % ) , hip ( 5.8 % ) and h and ( 3.1 % ) . Of the prevalent cases 26.8 % had OA in multiple joints . By the year 2032 , the proportion of the population aged ≥45 with doctor-diagnosed OA is estimated to increase from 26.6 % to 29.5 % ( any location ) , from 13.8 % to 15.7 % for the knee and 5.8 - 6.9 % for the hip . CONCLUSION In 2032 , at least an additional 26,000 individuals per 1 million population aged ≥45 years are estimated to have consulted a physician for OA in a peripheral joint compared to 2012 . These findings underscore the need to address modifiable risk factors and develop new effective OA treatments Introduction We aim ed to identify the effects of intraoperative applied leukocyte-poor platelet-rich plasma ( LP-PRP ) during knee arthroscopy for degenerative lesions involving pain , function and quality of life . Methods We performed a r and omized controlled , double-blind trial ( RCT ) including 58 patients for arthroscopic knee surgery for cartilage or meniscal degeneration with allocation into the LP-PRP ( n = 24 ) or control group ( n = 34 ) . During arthroscopy , LP-PRP was injected intra-articular in the intervention group . At baseline , 6 weeks , 6 months and 12 months pain , function , and life quality were assessed . Results 91 % of enrolled patients were available for 12 months follow-up . Pain was significantly lower in the LP-PRP group ( VAS 0.9 . vs. 2.3 ) at 6 ( p = 0.008 ) but not at 12 months ( VAS 1.0 vs. 1.6 , p = 0.063 ) . LP-PRP application improved the Lysholm Score at 6 ( 77.5 vs. 65.6 , p = 0.033 ) and 12 months ( 83.2 vs.70.0 , p = 0.007 ) . Assessment of life quality ( SF-36 ) concerning the physical component summary was significantly higher at 6 weeks ( 33.9 vs. 25.6 , p = 0.001 ) and 6 months ( 29.9 vs. 27.1 , p = 0.027 ) in the LP-PRP group but equal at 1 year ( 31.4 vs. 30.1 , p = 0.438 ) . Conclusions Intraoperative application of LP-PRP may enhance pain reduction and gain of knee function within 6–12 months compared to arthroscopy alone . Level of evidence II , r and omized controlled clinical trial with reduced power . Clinical Trials.gov identifierNCT02189408 [ Purpose ] To assess the effects of different numbers of platelet-rich plasma ( PRP ) applications on pain and physical function in grade 3 knee osteoarthritis ( OA ) . [ Subjects and Methods ] A total of 102 patients with grade 3 knee OA were r and omly divided into three groups : Group 1 received a single injection of PRP , Group 2 received two injections of PRP two weeks apart , Group 3 received three injections of PRP at 2-weeks intervals . All patients were evaluated with a visual analog scale ( VAS ) , the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , and the Timed-Up and Go test ( TUG ) before the treatment and at 1 , 3 and 6 months after the treatment . [ Results ] Ninety-eight patients ( 15 males , 83 females ) completed the study . The mean ages of the patients were 53.5±6.6 , 54.9±5.3 , and 55.1±5.6 years in Group 1 , Group 2 , and Group 3 , respectively . Statistically significant improvements were noted in all of the evaluated measures in all of the groups . The mean differences of Group 1-Group 2 and Group 1-Group 3 WOMAC total , WOMAC pain , WOMAC stiffness , and WOMAC function scores were statistically significant . [ Conclusion ] PRP is an effective treatment for functional status and pain in moderate knee osteoarthritis and a minimum of two injections is appropriate Objective To compare the outcome of matrix-induced autologous chondrocyte implantation ( MACI ) and bone marrow aspirate concentrate (BMAC)–derived multipotent stem cells ( MSCs ) implantation in patellofemoral chondral lesions , using the same HYAFF11 scaffold . Methods From January 2005 to December 2010 , 37 patients with patellofemoral chondral lesions were prospect ively followed up , for a minimum of 3 years ; 19 of these patients were treated with  MACI  and 18 with BMAC . Radiographs , magnetic resonance imaging , and clinical scores ( International Knee Documentation Committee , Knee Injury and Osteoarthritis Outcome Score , visual analog scale , and Tegner ) were collected preoperatively , at 2-year and final follow-up . Five patients of MACI and 6 of the BMAC group underwent second-look arthroscopy ; 4 patients of each group consented to a concomitant biopsy . Results No adverse reactions or postoperative infections were noted . Baseline characteristics were similar in both groups ( P > 0.05 ) . Both groups showed significant improvement in all scores , from preoperative to final follow-up ( P = 0.001 ) , but there was no significant difference in improvement between the 2 groups , except for the IKDC subjective score ( P = 0.015 ) , which favored the BMAC group . Deterioration in MACI and improvement in  BMAC  group scores were noticed , from 2-year to final follow-up , but was nonsignificant . MACI patients with trochlear lesions showed better results than patellar lesions , while location was not a prognostic factor in the BMAC group . MRI showed complete filling of the defects in 76 % of patients in MACI and 81 % of patients in BMAC , and histological analysis revealed hyaline-like features . Conclusion Both techniques are viable and effective for large patellofemoral chondral lesions at minimum 3-year follow-up Objective This study aim ed to find a simple , cost-effective , and time-efficient method for the preparation of platelet-rich plasma ( PRP ) , so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee . Design The study was design ed as a prospect i ve , cohort study with a control group . A total of 120 patients with Grade 1 , 2 , or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study . One group of patients was treated using three intra-articular applications of PRP , and the second group of patients was given three injections of hyaluronic acid . Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale . Results On average , a 4.5-fold increase in platelet concentration was obtained in the PRP group . No severe adverse events were observed . Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up . Conclusions Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis . Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed PURPOSE The purpose of this study was to compare histologic and magnetic resonance imaging ( MRI ) evaluation of articular cartilage regeneration in patients with chondral lesions treated by arthroscopic subchondral drilling followed by postoperative intra-articular injections of hyaluronic acid ( HA ) with and without peripheral blood stem cells ( PBSC ) . METHODS Fifty patients aged 18 to 50 years with International Cartilage Repair Society ( ICRS ) grade 3 and 4 lesions of the knee joint underwent arthroscopic subchondral drilling ; 25 patients each were r and omized to the control ( HA ) and the intervention ( PBSC + HA ) groups . Both groups received 5 weekly injections commencing 1 week after surgery . Three additional injections of either HA or PBSC + HA were given at weekly intervals 6 months after surgery . Subjective IKDC scores and MRI scans were obtained preoperatively and postoperatively at serial visits . We performed second-look arthroscopy and biopsy at 18 months on 16 patients in each group . We grade d biopsy specimens using 14 components of the International Cartilage Repair Society Visual Assessment Scale II ( ICRS II ) and a total score was obtained . MRI scans at 18 months were assessed with a morphologic scoring system . RESULTS The total ICRS II histologic scores for the control group averaged 957 and they averaged 1,066 for the intervention group ( P = .022 ) . On evaluation of the MRI morphologic scores , the control group averaged 8.5 and the intervention group averaged 9.9 ( P = .013 ) . The mean 24-month IKDC scores for the control and intervention groups were 71.1 and 74.8 , respectively ( P = .844 ) . One patient was lost to follow-up . There were no notable adverse events . CONCLUSIONS After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions , postoperative intra-articular injections of autologous PBSC in combination with HA result ed in an improvement of the quality of articular cartilage repair over the same treatment without PBSC , as shown by histologic and MRI evaluation . LEVEL OF EVIDENCE Level II , r and omized controlled trial ( RCT ) PURPOSE This multicenter , double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret ( BTI Biotechnology Institute , Vitoria-Gasteiz , Spain ) , an autologous biological therapy for regenerative purpose s , versus hyaluronic acid ( HA ) as a short-term treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA ( 3 injections on a weekly basis ) . The primary outcome measure was a 50 % decrease in knee pain from baseline to week 24 . As secondary outcomes , we also assessed pain , stiffness , and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index ; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International St and ing Committee for Clinical Trials Response Criteria Initiative ( OMERACT-OARSI ) ; and safety . RESULTS The mean age of the patients was 59.8 years , and 52 % were women . Compared with the rate of response to HA , the rate of response to PRGF-Endoret was 14.1 percentage points higher ( 95 % confidence interval , 0.5 to 27.6 ; P = .044 ) . Regarding the secondary outcome measures , the rate of response to PRGF-Endoret was higher in all cases , although no significant differences were reached . Adverse events were mild and evenly distributed between the groups . CONCLUSIONS Plasma rich in growth factors showed superior short-term results when compared with HA in a r and omized controlled trial , with a comparable safety profile , in alleviating symptoms of mild to moderate osteoarthritis of the knee . LEVEL OF EVIDENCE Level I , r and omized controlled multicenter trial Objectives : To determine and compare the effects of autologous platelet rich plasma ( PRP ) and hyaluronic acid ( HA ) for the treatment of osteoarthritis of the knee . Methods : This prospect i ve study included 150 patients affected by severe osteoarthritis of the knee . Gonarthrosis was grade d using the Kellgren-Lawrence and Albhack radiographic classification scale . 150 patients were r and omized into 2 study groups .In the PRP group ( n=55 ) three intraarticular injection were applied and the control group ( n=55 ) received 3 intra-articular injections of high molecular weight HA . An unblinded physician performed infiltration once a week for 3 weeks into the knee affected by clinical ly relevant gonarthrosis ( in both groups ) . All patients were evaluated with the Western Ontario and McMaster ( WOMAC ) score and visual pain scale before the infiltration and at 3 , 6 , and 12 months after the first injection . Results : No severe adverse events was observed . Statistically significant better results in the WOMAC score and visual pain scale was determined in PRP group than HA group at 3 months and 6 months follow up . The cost of the application for the PRP group was lower than that of the HA group . At 12 months ' of follow-up , PRP and HA treatments offered similar results . Conclusion : The results of this study have shown the application of autologousPRP to be a safe , effective and low-cost method for treating OA tan HA . However , further studies are required for a more clear Background : Platelet-rich plasma ( PRP ) injections have become an intriguing treatment option for osteoarthritis ( OA ) , particularly OA of the knee . Despite the plethora of PRP-related citations , there is a paucity of high-level evidence that is comparable , cohort specific , dose controlled , injection protocol controlled , and double-blinded . Purpose : To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma ( ACP ) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration ( FDA ) . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : In accordance with FDA protocol , patient selection was based on strict inclusion /exclusion criteria ; 114 patients were screened , and 30 were ultimately included in the study . These patients were r and omized to receive either ACP ( n = 15 ) or saline placebo ( n = 15 ) for a series of 3 weekly injections . Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores served as the primary efficacy outcome measure . Patients were followed for 1 year . Results : No adverse events were reported for ACP administration . Furthermore , the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups . However , in the ACP group , WOMAC scores at 1 week were significantly decreased compared with baseline scores , and the scores for this group remained significantly lower throughout the study duration . At the study conclusion ( 12 months ) , subjects in the ACP group had improved their overall WOMAC scores by 78 % from their baseline score , compared with 7 % for the placebo group . Conclusion : ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA . No adverse events were reported for ACP administration . After 1 year , WOMAC scores for the ACP subjects had improved by 78 % from their baseline score , whereas scores for the placebo control group had improved by only 7 % . Other joints affected with OA may also benefit from this treatment PURPOSE To analyze the results of the use of intra-articular cultured autologous bone marrow-derived mesenchymal stem cell ( MSC ) injections in conjunction with microfracture and medial opening-wedge high tibial osteotomy ( HTO ) . METHODS Fifty-six knees in 56 patients with unicompartmental osteoarthritic knees and genu varum were r and omly allocated to the cell-recipient group ( n = 28 ) or control group ( n = 28 ) . Patients who had a joint line congruity angle of more than 2 ° , malalignment of the knee from femoral causes , a fixed flexion deformity , or age older than 55 years were excluded . All patients underwent HTO and microfracture .  The cell-recipient group received intra-articular injection of cultured MSCs with hyaluronic acid 3 weeks after surgery , whereas the control group only received hyaluronic acid . The primary outcome measure was the International Knee Documentation Committee ( IKDC ) score at intervals of 6 months , 1 year , and 2 years postoperatively . Secondary outcome measures were Tegner and Lysholm clinical scores and 1-year postoperative Magnetic Resonance Observation of Cartilage Repair Tissue ( MOCART ) scores . RESULTS The median age of the patients was 51 years , with a mean body mass index of 23.85 . Both treatment arms achieved improvements in Tegner , Lysholm , and IKDC scores . After adjustment for age , baseline scores , and time of evaluation , the cell-recipient group showed significantly better scores . The effect of treatment showed an added improvement of 7.65 ( 95 % confidence interval [ CI ] , 3.04 to 12.26 ; P = .001 ) for IKDC scores , 7.61 ( 95 % CI , 1.44 to 13.79 ; P = .016 ) for Lysholm scores , and 0.64 ( 95 % CI , 0.10 to 1.19 ; P = .021 ) for Tegner scores . Magnetic resonance imaging scans performed 1 year after surgical intervention showed significantly better MOCART scores for the cell-recipient group . The age-adjusted mean difference in MOCART score was 19.6 ( 95 % CI , 10.5 to 28.6 ; P < .001 ) . CONCLUSIONS Intra-articular injection of cultured MSCs is effective in improving both short-term clinical and MOCART outcomes in patients undergoing HTO and microfracture for varus knees with cartilage defects . LEVEL OF EVIDENCE Level II , r and omized controlled trial Background : Specific growth factors have been proposed as therapeutic proteins for cartilage repair . Hypothesis : Platelet-rich plasma ( PRP ) provides symptomatic relief in early osteoarthritis ( OA ) of the knee . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 78 patients ( 156 knees ) with bilateral OA were divided r and omly into 3 groups . Group A ( 52 knees ) received a single injection of PRP , group B ( 50 knees ) received 2 injections of PRP 3 weeks apart , and group C ( 46 knees ) received a single injection of normal saline . White blood cell (WBC)–filtered PRP with a platelet count 3 times that of baseline ( PRP type 4B ) was administered in all . All the groups were homogeneous and comparable in baseline characteristics . Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) question naire before treatment and at 6 weeks , 3 months , and 6 months after treatment . They were also evaluated for pain by a visual analog scale , and overall satisfaction with the procedure and complications were noted . Results : Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months , with slight worsening at the 6-month follow-up . The mean WOMAC scores ( pain , stiffness , physical function , and total score ) for group A at baseline were 10.18 , 3.12 , 36.56 , and 49.86 , respectively , and at final follow-up were 5.00 , 2.10 , 20.08 , and 27.18 , respectively , showing significant improvement . Similar improvement was noted in group B ( mean WOMAC scores at baseline : 10.62 , 3.50 , 39.10 , and 53.20 , respectively ; mean WOMAC scores at final follow-up : 6.18 , 1.88 , 22.40 , and 30.48 , respectively ) . In group C , the mean WOMAC scores deteriorated from baseline ( 9.04 , 2.70 , 33.80 , and 45.54 , respectively ) to final follow-up ( 10.87 , 2.76 , 39.46 , and 53.09 , respectively ) . The 3 groups were compared with each other , and no improvement was noted in group C as compared with groups A and B ( P < .001 ) . There was no difference between groups A and B , and there was no influence of age , sex , weight , or body mass index on the outcome . Knees with Ahlback grade 1 fared better than those with grade 2 . Mild complications such as nausea and dizziness , which were of short duration , were observed in 6 patients ( 22.2 % ) in group A and 11 patients ( 44 % ) in group B. Conclusion : A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA . The results , however , deteriorate after 6 months . Both groups treated with PRP had better results than did the group injected with saline only
OBJECTIVE The purpose of the present investigation is to conduct a systematic review of the literature to review the clinical results of platelet rich plasma ( PRP ) and mesenchymal stem cell treatments ( MSC ) ( biologics ) for articular cartilage lesions and osteoarthritis of the knee .