Autologous chondrocyte implantation provides good long-term clinical results in the treatment of knee osteoarthritis: a systematic review.

PURPOSE: To evaluate the mid- and long-term efficacy of autologous chondrocyte implantation (ACI) and matrix-assisted chondrocyte implantation (MACI) to treat patients with knee cartilage defects in the presence of osteoarthritis (OA). METHODS: PubMed and Cochrane databases were systematically searched for studies describing the treatment of knee OA with ACI or MACI (Kellgren-Lawrence (KL) ≥ 1, minimum follow-up 36 months). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and included Lysholm, Western Ontario McMaster University and International Knee Documentation Committee scores. RESULTS: Of the 127 full-text articles assessed for eligibility, only five studies were selected based on inclusion/exclusion criteria (2 on ACI and 3 on MACI). In both groups, the defects were mainly located at femoral level, size 2.2-15.1 cm2 in the ACI and 2.0-7.6 cm2 in the MACI group. ACI was mostly used for patients affected by KL I, whereas MACI for patients with KL II-IV. The data obtained from 235 patients (161 ACI, 74 MACI) showed that ACI and MACI sustained stable clinical improvements up to 11 and 15 years, respectively, with a failure rate of about 10% up to 11 years. Scarce biological details regarding chondrocyte implantation were reported. CONCLUSIONS: ACI and MACI procedures for the treatment of knee cartilage lesions associated to OA showed long-term success and allowed delaying arthroplasty. Additional trials reporting homogenous data and precise patient characterization are needed to conduct an effective literature meta-analysis and identify the clinical relevance of these procedures. LEVEL OF EVIDENCE: IV.

Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.

During endochondral bone development, a complex process that leads to the formation of the majority of skeletal elements, mesenchymal cells condense, differentiating into chondrocytes and producing the foetal growth plate. Chondrocytes progressively hypertrophy, induce angiogenesis and are then gradually replaced by bone. Epidermal Growth Factor (EGF), one of many growth factors, is the prototype of the EGF-ligand family, which comprises several proteins involved in cell proliferation, migration and survival. In bone, EGF pathway signalling finely tunes the first steps of chondrogenesis by maintaining mesenchymal cells in an undifferentiated stage, and by promoting hypertrophic cartilage replacement. Moreover, EGF signalling modulates bone homeostasis by stimulating osteoblast and osteoclast proliferation, and by regulating osteoblast differentiation under specific spatial and temporal conditions. This evidence-based narrative review describes the EGF pathway in bone metabolism and endochondral bone development. This comprehensive description may be useful in light of possible clinical applications in orthopaedic practice. A deeper knowledge of the role of EGF in bone may be useful in musculoskeletal conditions which may benefit from the modulation of this signalling pathway.Key messagesThe EGF pathway is involved in bone metabolism.EGF signalling is essential in the very early stages of limb development by maintaining cells in an undifferentiated stage.EGF pathway positively regulates chondrocyte proliferation, negatively modulates hypertrophy, and favours cartilage replacement by bone.EGF and EGF-like proteins finely tune the proliferation and differentiation of bone tissue cells, and they also regulate the initial phases of endochondral ossification.

Management of gunshot wound to the lumbosacral spine in a 17-year-old girl without neurological impairment.

We report the case of a young girl (17-year-old) wounded by an accidental gunshot. The bullet entered through the skin midline over the navel area, passed through the stomach perforating the vena cava and, by breaking the right pedicle of L4, moved inside the vertebral canal (bridging the cauda equina) stopping just in front of the body of S2. Because of the sudden onset of acute abdomen due to a massive retroperitoneal hematoma, the patient underwent emergency explorative laparotomy with the evacuation of the hematoma and the suture of the perforated cava vein, the peritoneum, and the stomach. No neurological deficits were observed after the gunshot. Two weeks later, the patient underwent spinal surgery to remove the bullet from the spinal canal, which was performed successfully without any instrumentation and with no onset of new neurological signs and symptoms or surgery-related complications. Patient was discharged on day 9 after surgery in good general conditions.

Modifications of spinopelvic parameters and acetabular orientation after spinal surgery for adult deformity in patient who underwent bilateral total hip arthroplasty.

The spine and the hip are two anatomical districts that have close biomechanical relationship. The management of their degenerative disorders involves an in-depth biomechanical analysis of the patient, in order to define the proper hip-spine relation, using different biomechanical classifications that have been proposed in recent years. The changes in the spino-pelvic and acetabular parameters induced by prosthetic hip surgery and spinal surgery must be carefully evaluated, calculated and foreseen in the pre-operative phase, as they play a crucial role in defining the clinical success or failure of the operations. In this paper we present a case of a patient who underwent spinal surgery after a bilateral THA analyzing both spino-pelvic parameters and acetabular orientation and highlighting the strict relations between spine and hip.

Use of lordotic cages in L5-S1 Anterior Lumbar Interbody Fusion (ALIF) procedures

Anterior Lumbar Interbody Fusion (ALIF) has gained popularity in the last few years, thanks to its numerous advantages. Recently the use of lordotic cages has been described, allowing theoretically a better lordosis restoration of the lumbar disc space. We described the results obtained with the use of lordotic cages in 27 patients who underwent ALIF procedure for L5-S1 disc degenerative disease, in terms of segmental lordosis and global lumbar lordosis changes.

Two-stage total hip arthroplasty for septic arthritis through the minimally invasive direct anterior approach.

The use of minimally invasive direct anterior approach to perform total hip arthroplasty is gaining increasing popularity for its short-term advantages, compared to other approaches. Nevertheless, its use in hip revision surgery has been criticized. We report here the first case of hip septic arthritis treated with two-stage THA through this tissue-sparing approach, with good implant positioning and functional results.

Kinematic versus mechanical alignment in total knee arthroplasty: a preliminary study.

Despite the great advances of the technology in the joint prosthesis and the high execution rate of total knee arthroplasty (TKA), there are still about 15% of clinical unsatisfactory rate in this surgery. TKAs are currently performed using a mechanical alignment of the knee, correcting varus/valgus deformities with the purpose to achieve a longer implant survivorship, but this surgical technique results in an alteration of the normal knee kinematics. Nowadays, the idea to restore the pre-arthritic alignment of the knee with the goal to obtain a normal kinematics and better functional results becomes more and more consistent and the kinematic alignment (KA) was developed as alternative to the mechanical one. The aim of this preliminary study is to analyse the functional outcomes in patients who underwent KA-TKA in the short-term follow-up and to compare them with those obtained in patients treated by the mechanical alignment (MA) TKA. Therefore, skeletally mature patients, with no history of previous knee surgical procedures, who underwent isolated TKA for knee osteoarthritis, were included in this study. The patients were prospectively divided into two homogeneous groups according to the different surgical techniques performed (KA-TKA and MA-TKA groups). Clinical and functional scores (VAS, KOOS-PS, MCS-12, Final KSS, and Functional KSS) were collected pre- and postoperatively at a mean follow-up of 3 three months. As a result, 26 patients were included in the study, with a mean age of 69.3±7.61 years old (range: 55 - 84 years old). There were 38.5% male and 61.5% female. There were 13 patients in KA-TKA and 13 patients in MA-TKA. Three months after surgery each of the scores tested demonstrated statistically significant better outcomes in KA-TKA, compared to the MA-TKA group. MCS-12 resulted comparable in the two study groups. This preliminary study compares the short-term clinical and functional outcomes between KA and MA in total knee replacement. Further studies are required to confirm these results and to extend the sample size to obtain reliable clinical evidences.

Histological assessment of new bone formation with biomimetic scaffold in posterolateral lumbar spine fusion.

Spinal fusion procedures often require the use of bone grafts (autograft or allograft) to help bone healing and to increase stability. However, the application of autografts is frequently limited by donor site morbidity. In recent years, different synthetic bone substitutes have been introduced in the clinical practice to overcome these limitations. The purpose of this paper is to report a case where a biomimetic, synthetic and osteoconductive bone graft substitute was successfully implanted in a patient during lumbar spine arthrodesis. The case of a 58-year-old female subjected to lumbar spine arthrodesis with bone augmentation is described. The bone graft substitute RegenOss® (Finceramica, Faenza, Italy) was implanted during spinal arthrodesis. The successful bone integration was evaluated by X-rays. After 11 months, the patient underwent a second surgery due to spine imbalance; the debris of the bone graft was therefore collected and analyzed by macroscopic evaluation and by histology. The bone substitute was successfully implanted during a spinal arthrodesis procedure. Histologic evaluation of the removed bone graft debris showed the complete resorption of the implant and the formation of new bone, which was well integrated with the host bone. This bone substitute may represent a safe and effective alternative to autologous bone grafts, avoiding adverse events related to donor-site morbidity.

Bilateral osteochondritis dissecans of the patella in an adolescent skier with patellofemoral maltracking treated with pulsed electromagnetic field therapy.

Juvenile osteochondritis dissecans of the knee typically occurs in young athletes, and usually localizes on the medial femoral condyle. Bilateral localization is uncommon. Patellofemoral involvement is rare, mainly found in basketball and soccer players, and never related to patellofemoral congenital problems such as trochlear dysplasia. We report here the first case, to our knowledge, of bilateral juvenile osteochondritis dissecans with patellar localization in a young skier with patellofemoral maltracking and trochlear dysplasia.

Combined circular external fixation and flexible intramedullary nailing for pediatric bilateral open tibia fractures in blast injury.

Management of blast injuries with open fractures and extensive soft tissue damage in pediatric patients is a challenging task even in experienced hands. This article reports the case of an 8-year-old boy with bilateral open tibia fractures and soft tissue loss due to the accidental explosion of a skyrocket. After the emergency procedures with lavage, debridement and temporary bone stabilization, we performed the definitive reconstruction surgery using a combined circular external fixation and flexible intramedullary nailing technique on both legs. This technique allowed easy access to the wounds for plastic surgery procedures and early bilateral weight bearing. All implants were removed within 6 months, the fractures healed with good axial alignment and the patient returned to his preinjury activities one year after the trauma. In this case, the combined use of circular external fixation and flexible intramedullary nailing ensured optimal fractures stabilization, minimizing the damage to the soft tissues and the obstruction for plastic surgeons. We believe that this technique should be considered in pediatric patients with open fractures of the lower limbs and extensive soft tissue injuries.

Bilateral total hip arthroplasty through minimally invasive direct anterior approach after Legg-Calvé-Perthes disease.

Bilateral secondary osteoarthritis of the hip may affect also young patients following bilateral hip diseases such as slipped capital femoral epiphysis and developmental hip dysplasia. We report the case of an 18- year old male with a previous diagnosis of Legg-Calvé-Perthes disease who underwent a bilateral total hip arthroplasty through minimally invasive direct anterior approach, with optimal results at 1-year follow up.

Correction of post traumatic tibial varus deviation with hexapodalic external fixator.

Physeal fractures are typical in childhood and for their involvement of the germinal layer of the physis they can be followed by growth complications. Axial deviation is one of these. Considering the young age of the patients it is critical to restore articular correct alignment with the least invasive surgery possible. We report here the first case of correction of post traumatic tibial varus deviation with exapodalic external fixator.

When math meets surgery: how to improve femoral interference screw alignment in ACL reconstruction. A cadaveric study.

Transtibial femoral tunnel drilling is still an alternative technique in ACL reconstruction. Femoral interference screw divergence is a potential pitfall associated with transtibial tunnel technique, as angles greater than 15° jeopardize graft fixation. Our mathematical model theorizes the proper degrees of knee flexion during femoral screw insertion and the correct screwdriver position to obtain a minimal divergence of the screw in the femoral tunnel. The cadaveric study confirms our method. Mathematical model: using rototranslation matrices, a correlation is demonstrated between the ACLtibial- guide angle, the knee flexion, and the screwdriver position. A theoretical minimal divergence between femoral interference screw and the femoral tunnel is obtainable following these assumptions: 1) knee hyperflexion during femoral screw insertion is obtained adding a flexion corresponding to the ACL-tibial-guide angle to the flexion while drilling the femoral tunnel; 2) screwdriver position (through the AM portal) is kept parallel to tibial plateau at a rotation of 15° medial to tibial sagittal plane. Cadaveric study: 24 cadaver knees were used. The transtibial tunnel was drilled with an 8 mm drill bit with the help of an ACL tibial guide set at 55°. To simulate femoral tunnel direction, a 2.4 mm K. wire was drilled through the femur with a transtibial 7 mm offset femoral drill guide. To simulate the femoral screw direction, a second 2.4 mm K. wire was drilled from the femoral entry point of the first wire through the femur, with a cannulated screwdriver. Screwdriver direction and knee flexion during the simulation were obtained following two different methods: GROUP A (mathematical model group, 12 knees), screwdriver direction and knee flexion were calculated following the mathematical model; in GROUP B (control group, 12 knees), knee hyperflexion and screwdriver medialization were manually obtained by a senior surgeon. The divergence between the femoral interference screw and the femoral tunnel was identified as the angle formed by the two wires, measured on the plane formed by the direction of the wires. Mean divergence angles between the K. wires were significantly different (p< 0.05) between the groups: GROUP 1 (mathematical rule): 7.25° (SD 2.2); GROUP 2 (free-hand technique): 17.3° (SD 2.9). Our study shows that a minimal divergence between the femoral tunnel and the screwdriver can be achieved simply by following a mathematical rule for correct intraoperative knee flexion and screwdriver position without the need for any specialized instrumentation. Namely, during femoral interference screw insertion through the anteromedial portal: 1) the correct knee flexion is the sum between the knee flexion angle while drilling the transtibial femoral tunnel AND the ACL tibial guide angle used during tibial tunnel drilling; 2) Correct screwdriver position is parallel to the tibial plateau, engaging the femoral tunnel with a position of 15° medial to tibial sagittal plane. This simple concept has clinical relevance in helping the surgeons in obtaining an optimal alignment between the femoral tunnel and the femoral interference screw during transtibial ACL reconstruction. Furthermore, following the assumptions of this study, a starting knee flexion angle around 70° during femoral tunnel drilling seems preferable for ACL reconstruction when the transtibial tunnel technique is used. Indeed, because ACL-tibial-guide angles range commonly from 50° to 60° and in vivo, the maximal intraoperative knee flexion attainable is 130°, a starting knee flexion around 70° is optimal to allows for adding flexion angles up to 60° before reaching the physiological limit value of 130°.

Hamstring grafts are tenogenic constructs for ACL reconstruction and Pulsed Electromagnetic Fields improve tendon specific markers expression. An in-vitro study.

Hamstring tendons represent one of the commonest autologous graft used during ACL reconstruction. The harvest of the tendon and the time of tendon processing on the operating table, together with the pretensioning maneuvers and the permanence out of the joint during the time of surgery, might impair tendon derived cells (TCs) viability. The aim of the study was: i) to assess the effective viability of the TCs at the end of the surgical procedure; ii) to investigate if TCs viability and the expression of tendon specific markers may be improved through exposure to prolonged pulsed electromagnetic fields (PEMF) similar to that of clinical practice. Remnants of semitendinosus and gracilis tendons (discarded at the end of the ACL reconstruction) were collected from 13 healthy donors. To isolate TCs, the tendon tissue was minced and digested enzymatically with 0.3% type I collagenase in DMEM with continuous agitation for 15 h at 37°C. The isolated nucleated cells were then plated at 5x103 cells/cm2 in a complete medium composed of DMEM, 10% fetal bovine serum, 50 U/ml Penicillin, 50 mg/ml Streptomycin, 2 mM L-glutamine, and supplemented with 5 ng/ml basic fibroblast growth factor (b-FGF). They were maintained at 37 °C in a humidified atmosphere with 5% CO2, changing culture medium every 3 days. When they reached 80-90% of confluence, the cells were detached by incubation with trypsin/EDTA and then cultured at a density of 5x103 cells/cm2. TCs were cultured in complete medium for 7, 14, 21 days (in chamber slides, to optimize the final immunofluorescence analysis). The following cell cultures were set up: i) TCs cultured with differentiation medium + exposure to PEMF 8 h/day; ii) TCs cultured with differentiation medium without exposure to PEMF. The stimulation with PEMF was generated by a pair of electrical coils, connected with the generator of pulsed electromagnetic fields (PEMF generator system IGEA, Carpi, Italy, intensity of magnetic field = 1.5 mT, frequency = 75 Hz). At day 0, day 7, day 14 and day 21 immunofluorescence analysis was performed to evaluate the expression of tendon specific markers (collagen type I, collagen type VI, scleraxis) and proliferative markers (PCNA, beta-catenin). The TCs from the hamstring tendon fragments at the end of the ACL reconstruction were alive and they expressed markers of proliferation and tendon phenotype at the end of the culture period. The TCs in the presence of PEMF 8h/day showed a greater production of collagen type I, collagen type VI and scleraxis than TCs cultured without PEMF (p<0.05). The expression of these markers increased from 7 to 21 days of culture. The expression of proliferative markers in the presence of PEMF stimulus was significantly lower (p<0.05) than that of TCs cultured without PEMF. Hamstring tendons are not simple "tenoconductive" scaffolds but biologic alive tenogenic constructs rich in cells that can sustain tenogenic behavior and tendon matrix synthesis. Prolonged exposure to PEMF improves their phenotype. Thus, from a clinical perspective, the use of PEMF may represent a possible future strategy to positively influence the early phase of graft remodeling and, ultimately, improve the ligamentization process. Following these concepts, further studies might also exploit the anabolic role of PEMF as an adjunctive postoperative strategy in different tendon pathologies.

O'nil Anteversa® mini-plate for stable hip fracture: first experience considerations and outcomes.

Hip fractures are associated with a 20% one-year mortality and a 50% loss of function. Over 700,000 deaths are estimated to occur annually worldwide following hip fractures. Concern exist regarding which is the best implant for extracapsular fractures fixation. For a correct positioning of the cephalic screw, a new plate (O'Nil Anteversa® mini-plate, Intrauma, Torino, Italy) with a fixed 8°of anteversion in the axial plane was developed. A total of 22 patients with an intertrochanteric fracture underwent surgery with Anteversa® mini-plate between October 2016 and April 2017. Data collected included patients' age at surgery, gender, fracture type, operative side, surgeon, type of implant, TAD, CalTAD and TADCalTAD. All patients underwent clinical and radiographic evaluations according to the AO Surgery Reference classification. The mean TAD, CalTAD and TADcalTAD for the entire population of study were, respectively, 20.18±7.5 mm, 20.45±7.25 mm, and 40.62±14.44 mm. The mean TAD, CalTAD and TADcalTAD of those patients who experienced mobilisation of the cephalic screw were, respectively, 20.26±5.87 mm, 19.53±5.47 mm, and 39.8±11.16 mm. Three patients experienced mobilisation of the cephalic screw, and none of these had a TAD greater than 25 mm, a CalTAD greater of 25mm or a TADcalTAD greater than 50 mm. This type of device meets the essential requirements for a correct treatment of intertrochanteric fractures in elderly patients. However, the excessive need of attention in each step, and the consequent increased time of surgery, could be seen as a limitation for its use.

Fibula-pro-tibia transfer with external fixator after tibia fracture with extensive bone defect: a case report.

A 27-year-old girl suffered a tibial fracture with an extensive bone defect due to a major trauma. At first, she was treated with a plate with the purpose to obtain a fibula-pro-tibia transfer, without any improvement. At one-year-follow up, a non-union due to mechanical hardware failure was shown by x-ray. Thus, a second surgery was performed: the ipsilateral fibula was tightly wedged between the preserved proximal and distal third of tibia with an external fixator. We report a follow up of 1 year after the reconstruction that allowed a good bone healing and a remodeling with also further ossification of the periosteal sheath of the fibula.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II: treatment options.

The treatment of painful chronic tendinopathy is challenging. Multiple non-invasive and tendon-invasive methods are used. When traditional non-invasive treatments fail, the injections of platelet-rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra- or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.

Animal models for cartilage repair.

Cartilage lesions still represent an unsolved problem: despite the efforts of the basic and translational research, the regeneration of this tissue is far from being reached (1-3). Articular cartilage lesions can be divided in two main groups: superficial or partial defects and full-thickness defects (4, 5). Partial lesions are not able to self-heal because multipotent cells from the bone marrow cannot reach the area leading to a progressive degeneration of the tissue (6). Conversely, full-thickness injuries possess greater chances to heal because subchondral bone involvement allows for the migration of mesenchymal cells, which fill the damaged area (7, 8). However, healing occurs through the formation of a fibrocartilaginous tissue, which has different biomechanical and biological properties (9). Native hyaline cartilage has indeed specific biomechanical properties, which confer resistance to compressive and shear stresses; the reparative fibrocartilaginous tissue lacks these abilities, therefore, the surrounding healthy cartilage progressively degenerates. In the past years, several therapeutic strategies have been developed to restore the damaged cartilage, bone marrow stimulation (chondroabrasion, drilling, micro- or nano-fractures) and more recently, tissue engineering approaches (10-14). Some of these latter procedures have already been applied in clinical practice such as matrix-induced autologous chondrocyte implantation (MACI) (15) or osteochondral scaffold implantation (16). Generally, tissue engineering approaches are based on the combination of three main elements: cells (i.e. primary chondrocytes or multipotent mesenchymal cells), biocompatible scaffolds (i.e. polymers, composites, ceramics) and signaling molecules (i.e. growth factors). Moreover, several culture conditions (i.e. static or dynamic cultures) and biomechanical stimuli can be applied during the in vitro culture to promote tissue maturation (17-19). However, an in vivo culture is mandatory to validate a new engineered construct as the in vitro phase lacks the essential in vivo environmental stimuli and because the in vivo culture allows for the testing of the biocompatibility and safety of a new material (18, 19). Moreover, preclinical animal models are crucial to understand the molecular mechanisms of cartilage lesions favoring the development of new regenerative strategies (20, 21). in vivo studies on animal models should focus on the analysis of the cellular component, analyzing the maintenance of the cellular phenotype and the tumorigenicity; on the evaluation of the biocompatibility, toxicity and degradation of the biomaterial and on the assessment of the engineered construct. In this manuscript, we will review the most common preclinical animal models, which are used to understand cartilage biology and therefore to develop new tissue engineering strategies. We will focus on both small and large animal models highlighting their peculiarities, advantages and drawbacks.

Comparison of early functional outcomes between two different surgical approaches for total hip arthroplasty.

Total Hip Arthroplasty (THA) is considered the most successful treatment for advanced hip osteoarthritis. Different surgical approaches for THA are available and they have shown excellent outcomes in the long-term follow-ups. However, few studies have analyzed the functional outcomes in the first days after a THA surgery. The purpose of this study was to compare the early functional outcomes between two different surgical techniques: a minimally invasive direct anterior approach (mini-DAA) and a postero-lateral approach (PL). Twelve patients for each group were analyzed. Pre- and postoperative (3, 10, 30 and 90 days after surgery) Patient-Reported Outcome Measures (PROMs) were administered: HOOS, HHS, VAS and SF-12-v2 scores. Moreover, comparison between surgical operation time and blood loss were examined. PROMs showed a significant improvement in the SF-12-v2 in the mini-DAA group compared to the PL group at 3 days after surgery: this difference was maintained also after 10 and 30 days. In addition, HOOS and HHS were significantly ameliorated in the mini-DAA group starting 10 days from surgery. In both groups, a physiological pain reduction was observed in the first days after surgery; comparing it to the pre-surgical VAS values, we found a significant improvement in the scores for the mini-DAA group after 30 days. Moreover, we demonstrated a significant reduction in blood loss for the mini-DAA group. Surgical operation times were similar in the two groups; however, the duration of the mini-DAA procedure was shorter compared with the known literature. In this preliminary study, we demonstrated that the minimally invasive direct anterior approach for THA may lead to benefits in the early postoperative time, as it allows for an improvement in functional outcomes, a reduction of postoperative pain, a reduction of hospitalization time and consequent reduction of postoperative complications; therefore, this surgical approach may consent an early return to work and daily activities.

Evaluation of the use of autologous micro-fragmented adipose tissue in the treatment of knee osteoarthritis: preliminary results of a randomized controlled trial.

Articular cartilage injuries are still unsolved due to the limited intrinsic healing potential of this tissue. Unlike other tissues, inflammation in the synovial joint causes perpetual damage and progressively leads to the development of osteoarthritis. Previous in vitro and in vivo studies have demonstrated the efficacy of mesenchymal stem cells isolated from adipose tissue in modulating inflammation. In this study, we analyzed the role of these cells in modifying the pathological microenvironment present in knee osteoarthritis. This is an interventional, prospective, randomized, controlled study. Starting from June 2017, 39 patients with grade III and IV knee osteoarthritis of Kellgren-Lawrence were enrolled, aged between 45 and 75 years, with pain greater than or equal to 6 according to the VAS scale, without ligament instability, with an axial deviation not greater than 10° and with a BMI between 18 and 30. The control group underwent an arthroscopic debridement, while the experimental group underwent an arthroscopic debridement and a subsequent intra-articular injection of autologous micro-fragmented adipose tissue. Patients were evaluated before surgery and at 6 months after the procedure, by radiological analysis (MRI) and functional outcome measures. The main purpose of the study is to evaluate the symptomatic improvement by comparing the functional outcome scores between the two groups. At 6 months after treatment, preliminary results on 39 patients showed pain reduction and functional improvements in the experimental group without a significant difference due to the low number of patients. The radiological and biochemical analyses are still ongoing. To date, the study has not revealed any side effects. These preliminary results demonstrate an encouraging positive trend in the experimental group. Patient recruitment is still ongoing to finalize the statistical analyses and to confirm our hypothesis.