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Aim: To test the agreement between a newly developed micro-magnetic resonance imaging (MRI) analysis of the subchondral bone and the micro-computed tomography (CT) approach. ----- Methods: Samples obtained from 10 patients with osteoarthritis undergoing total hip arthroplasty were scanned with a 7.0 T micro-MRI. Proton density- weighted images and proton density-weighted images with fat suppression were obtained. The results were validated with a micro-CT device. Micro-MRI and micro-CT scans of the same sample were aligned, and regions of interest were delineated on equal areas of the sample. Bone volume fraction was calculated by using in-house plugins. The agreement between the methods was tested with Bland- Altman analysis. ----- Results: The agreement between the methods was good, with average difference of 2.167%. The differences between the methods were not significant (P=0.272, t test). ----- Conclusion: The novel micro-MRI approach could be used for subchondral bone analysis. With further optimization for clinical MRI machines, the approach can be also used in the diagnostics of hip osteoarthritis.

Background: Intra-articular osteoid osteoma (iaOO) can be found in 5.2% up to 10% of cases. They may cause non-specific symptoms, mimicking degenerative or traumatic pathologies. If iaOO is left untreated, it may lead to severe muscle atrophy, tenderness, swelling, and limited range of motion. Therefore, surgical treatment is recommended. The main goal of surgical treatment is complete removal or destruction of iaOO. ----- Aim: To evaluate the efficiency of arthroscopic removal of iaOO of the knee in our cases and cases available in the literature. ----- Methods: Analysis of available hospital records of four patients with iaOO of the knee treated by arthroscopic removal from August 2005 to December 2015 at our Department was performed. All patients had a diagnosis of iaOO confirmed by histopathologic analysis. Additional literature review of cases of iaOO of the knee available on PubMed and Google Scholar was made. All cases of iaOO of the knee treated by arthroscopic or arthroscopically assisted removal were reviewed in order to further evaluate the efficiency of the method. ----- Results: The average age of patients included in our study was 23.2 (range 16-37) years. The average duration of the symptoms prior to surgery was 14.2 (range 6-24) months. All of the patients had persistent knee pain. Three patients reported worsening of pain during the night, while two reported worsening of pain during activity. Three patients reported alleviation of pain on non-steroidal anti-inflammatory drugs (NSAIDs), while one patient reported partial alleviation of pain on NSAIDs. No intraoperative complications were noted, and the postoperative period was uneventful in all patients. The patients reported immediate pain relief in the postoperative period. No recurrence of the disease was noted in any of the patients during the follow-up period of at least 24 mo. The literature review revealed 14 cases with an average age of 27.6 (range 16-48) years and onset of symptoms 27.7 (range 6-108) months prior to surgery, with recurrence of the disease noted in a single case. ----- Conclusion: Arthroscopic removal is an efficient treatment method that allows excision of iaOO that is neither insufficient nor excessive, thus avoiding disease recurrence while obtaining adequate material for histopathologic analysis.

Background: Primary synovial chondromatosis (PSC) is a progressive disorder of unknown etiology resulting in formation of multiple loose bodies. If left untreated, it may lead to degenerative changes or malignant transformation to chondrosarcoma. Methods: Seventeen patients who underwent combined posterior and anterior ankle arthroscopy within the same operative session and had histologically confirmed PSC were included in this retrospective study. American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score was used to evaluate ankle function preoperatively and at a final follow-up. A 3-question survey was used to evaluate patient’s satisfaction at the final follow-up. Results: In 14 patients, loose bodies were found in both compartments of the ankle, in 2 only in the anterior compartment, and in 1 only in the posterior compartment. All patients had evident signs of synovial inflammation in both compartments. The AOFAS Ankle-Hindfoot score increased from the preoperative median score of 65 (range, 29-90) to 95 (range, 65-100) at the final follow-up. Fourteen patients reported they were extremely satisfied with the outcome, 1 was moderately satisfied, and 2 were dissatisfied. No cases of recurrence of synovitis or loose body formation were noted, nor any signs of malignant transformation during the follow-up period. Conclusion: We believe the risk of recurrence of PSC, which is in close relation to malignant transformation, can be minimized by performing a complete synovectomy of the ankle. Our experience and review of literature makes us believe that ankle PSC should be regarded as a whole joint disorder. Performing a combined posterior and anterior arthroscopic procedure within the same operative session should always be considered in patients with ankle PSC. Level of Evidence: Level IV, retrospective case series.

Aim To analyze clinical and functional effects of intra-articular injection of autologous micro-fragmented lipoaspirate (MLA) in patients with late stage knee osteoarthritis (KOA). Secondary aims included classifying cell types contributing to the treatment effect, performing detailed MRI-based classification of KOA, and elucidating the predictors for functional outcomes. Methods This prospective, non-randomized study was conducted from June 2016 to February 2018 and enrolled 20 patients with late stage symptomatic KOA (Kellgren Lawrence grade III, n = 4; and IV, n = 16) who received an intra-articular injection of autologous MLA in the index knee joint. At baseline radiological KOA grade and MRI were assessed in order to classify the morphology of KOA changes. Stromal vascular fraction cells obtained from MLA samples were stained with antibodies specific for cell surface markers. Patients were evaluated at baseline and 12-months after treatment with visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Results Three patients (15%) received a total knee replacement and were not followed up completely. Seventeen patients (85%) showed a substantial pattern of KOOS and WOMAC improvement, significant in all accounts. KOOS score improved from 46 to 176% when compared with baseline, WOMAC decreased from 40 to 45%, while VAS rating decreased from 54% to 82% (all P values were

Developmental dysplasia of the hip (DDH) represents a morphological abnormality characterized by the incongruity of femoral head and acetabulum. It ranges from mild dysplastic changes to complete dislocation. DDH has been associated with several hereditary and environmental risk factors, which could explain the incidence variability among different countries. Numerous genes may be involved in the disease etiology and progression. However, there are controversies in the literature regarding some of these genes. DDH-induced secondary osteoarthritis (OA) is characterized by changes in the macromolecule content of the cartilage and the expression of cartilage degradation markers. In addition, it exhibits a pattern of specific histological changes, with several reported differences between primary and DDH-induced secondary OA. The articular cartilage of patients with DDH shows specific radiological characteristics, including changes visible already in infancy, but also at pre- arthritic stages, early stages of OA, and in fully developed DDH- induced secondary OA. Although DDH has been extensively researched in different disease stages, the etiology of the disorder still remains uncertain. This review focuses on the current knowledge on the histomorphological status of the cartilage and the genetic background of DDH.

Liver fibrosis is a progressive pathological process resulting in an accumulation of excess extracellular matrix proteins. We discovered that bone morphogenetic protein 1-3 (BMP1-3), an isoform of the metalloproteinase Bmp1 gene, circulates in the plasma of healthy volunteers and its neutralization decreases the progression of chronic kidney disease in 5/6 nephrectomized rats. Here, we investigated the potential role of BMP1-3 in a chronic liver disease. Rats with carbon tetrachloride (CCl4)-induced liver fibrosis were treated with monoclonal anti-BMP1-3 antibodies. Treatment with anti-BMP1-3 antibodies dose- dependently lowered the amount of collagen type I, downregulated the expression of Tgfb1, Itgb6, Col1a1, and Acta2 and upregulated the expression of Ctgf, Itgb1, and Dcn. Mehanistically, BMP1-3 inhibition decreased the plasma levels of transforming growth factor beta 1(TGFb1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFb1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis.

Alkaptonuria (AKU) is a rare autosomal recessive metabolic disease caused by a disorder of phenylala- nine and tyrosine metabolism, resulting in accumulation and deposition of homogentisic acid (HGA) in the body. This deposition further causes progressive functional disorders in different organ systems, with the locomotor system being the most affected one. A specific triad of symptoms occurs in patients suffering from AKU: 1. at birth, a change of urine color is present when urine is exposed to air, 2. oc- currence of dark pigmentations in connective tissues becomes visible over time, 3. complications of the locomotor, urogenital and cardiovascular systems present gradually. Arthropathia ochronotica occurs in patients suffering from AKU due to precipitation and deposition of HGA in the joint tissue (cartilage, tendons, ligaments, menisci, etc.). The accumulation can be seen as small foci of blue-black pigmentations. HGA deposits in collagen fibers, causing tendons and liga- ments thickening. This causes them to be less resistant to mechanical forces, resulting in frequent rup- tures caused by minimal trauma. Also, the deposition facilitates cartilage degeneration, often requiring an operative treatment. The knees are the most commonly affected joints, while changes can be seen in the spine and other large joints. As there is no specific treatment, alleviation of symptoms is the only treatment option. It has the goal of increasing individual functionality and quality of life. As an option for end-stage treatment, joint replacement surgery proved to be effective. In the future, an enzyme replacement therapy or gene therapy may be developed to treat AKU successfully., Alkaptonurija (AKU) je rijetka autosomno recesivna metabolička bolest uzrokovana poremećajem metabolizma fenilalanina i tirozina, što rezultira nakupljanjem i taloženjem homogentizinske kiseline (HGA) u tijelu. Ovo taloženje uzrokuje progresivne funkcionalne poremećaje u različitim organskim sustavima, pri čemu je najčešće zahvaćen lokomotorni sustav. Specifična trijada simptoma javlja se u bolesnika koji pate od AKU: 1. pri rođenju je vidljiva promjena boje urina kada je urin izložen zraku, 2. pojava tamnih pigmentacija u vezivnom tkivu s vremenom postaje vidljiva, 3. postepeno se razvijaju komplikacije koje zahvaćaju lokomotorni, urogenitalni i kardiovaskularni sustav. Artropatija ohronotica javlja se u bolesnika koji pate od AKU zbog taloženja HGA u zglobnom tkivu (hrskavica, tetive, ligamenti, meniskusi itd.). Akumulacija se može vidjeti kao mala žarišta plavo-crnih pigmentacija. HGA se taloži u kolagenskim vlaknima, uzrokujući zadebljanje tetiva i ligamenata. Zbog toga su ona manje otporna na mehaničke sile, što rezultira čestim puknućima uzrokovanim minimalnom traumom. Također, taloženje ubrzava degeneraciju hrskavice, što dovodi do češće potrebe za operativnim liječenjem. Koljena su najčešće zahvaćena, dok se promjene također mogu vidjeti na kralježnici i drugim velikim zglobovima. Kako ne postoji specifično liječenje, ublažavanje simptoma jedina je opcija liječenja. Cilj mu je povećati individualnu funkcionalnost i kvalitetu života. Kao opcija za završnu fazu liječenja, ugradnja umjetnih zglobova pokazala se sigurnom i učinkovitom. U budućnosti se očekuje razvoj enzimske ili genske terapije za uspješno ciljano liječenje AKU.

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45− fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34−CD73±CD90±CD105−CD146± mature endothelial cells, CD31−CD34−CD73±CD90+CD105−CD146+ pericytes, CD31−CD34+CD73±CD90+CD105−CD146+ transitional pericytes, and CD31−CD34+CD73highCD90+CD105−CD146− supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated.

The lack of adequate mechanical stimulation and appropriate contact between acetabulum and femoral head results with developmental dysplasia of the hip (DDH). In DDH, hip joint forms normally during the organogenesis, but deforms during the fetal development. Acetabulum remains comparable in width with normal acetabulum, but has increased length and decreased depth, resulting in a poor coverage of the femoral head. In cases of severe hip subluxation and luxation due to DDH, the femoral head articulates with the external side of the iliac bone, forming a neoacetabulum in the position that was genetically predetermined to become bony tissue. A neoacetabulum is therefore formed under intermittent mechanical pressure, but never has the depth of a physiological acetabulum due to different forces at this new location. Over time, the depth of the neoacetabulum increases, and a crest is formed that obstructs reposition of the femoral head into the anatomic acetabulum. We hypothesize that the neoacetabulum on the iliac bone in DDH patients is formed of hyaline cartilage, despite the lack of genetic predisposition for hyaline cartilage formation in this area. We assume that as the femoral head migrates during development in such patients, joint capsular tissue interposes between the external side of the iliac bone and the femoral head, and a cartilaginous metaplasia of the capsule follows. This results in elongation of the acetabular cartilage in the same direction as the femoral head migrated. This assumption is based on the finding that in patients with hip luxation such interposed joint capsule showed signs of cartilaginous transformation. Furthermore, in the inner part of such joint capsules, proteoglycan production was notably higher than that of other non-cartilaginous tissue. Also, high expression of cartilaginous genes, which are usually not expressed in this tissue, was observed. Confirmation of this hypothesis would put a new perspective on the pathogenesis of DDH and could lead to better management or even prevention of this condition.

Anterior section of the hip joint capsule is innervated by femoral nerve and obturator nerve, and posterior section is innervated by the nerve to quadratus femoris muscle and occasionally by the superior gluteal (posterolateral region) and sciatic nerve (posterosuperior region). One of the regional anesthesia options for hip surgery is the fascia iliaca compartment block (FICB) that affects nerves important for hip innervation and sensory innervation of the thigh - femoral, obturator and lateral femoral cutaneous nerve. FICB can be easily performed and is often a good solution for management of hip fractures in emergency departments. Its use reduces morphine pre-operative requirement for patients with femoral neck fractures and can also be indicated for hip arthroplasty, hip arthroscopy and burn management of the region. Quadratus lumborum block (QLB ) is a block of the posterior abdominal wall performed exclusively under ultrasound guidance, with still unclarified mechanism of action. When considering hip surgery and postoperative management, the anterior QLB has shown to reduce lengthy hospital stay and opioid use, it improves perioperative analgesia in patients undergoing hip and proximal femoral surgery compared to standard intravenous analgesia regimen, provides early and rapid pain relief and allows early ambulation, thus preventing deep vein thrombosis and thromboembolic complications etc. However, some nerve branches responsible for innervation of the hip joint are not affected by QLB , which has to be taken into consideration. QLB has shown potential for use in hip surgery and perioperative pain management, but still needs to be validated as a reliable treatment approach., Prednji dio čahure zgloba kuka nerviraju n. femoralis i n. obturatorius, dok stražnji dio čahure inervira n. musculi quadratus femoris i povremeno n. glutealis superior (posterolateralni dio) i n. ischiadicus (posterosuperiorni dio). Jedna od mogućnosti za primjenu regionalne anestezije u kirurgiji zgloba kuka je blok odjeljka fascije iliace (FICB), koji zahvaća živce bitne za inervaciju kuka te senzornu inervaciju bedra – n. femoralis, n.obturatorius i n. cutaneus femoris lateralis. FICB se može izvesti relativno jednostavno i predstavlja dobru opciju za zbrinjavanje fraktura kuka u hitnim situacijama. Dokazano je kako smanjuje upotrebu morfija preoperativno u pacijenata s frakturom vrata femura, a može biti indicirani za artroplastiku kuka, artroskopije kuka te sanaciju opeklina u regiji bedra. Quadratus Lumborum blok (QLB ) spada u blokove stražnjeg abdominalnog zida te se provodi isključivo pod kontrolom ultrazvuka. Još uvijek nije razjašnjen točan mehanizam njegovog djelovanja. Dokazano je kako prednji QLB dovodi do smanjenja trajanja boravka u bolnici i smanjenja upotrebe opioida nakon operacija kuka. Također, pokazao se kao uspješnija metoda perioperativne analgezije u bolesnika u kojih se provodi zahvat na kuku ili proksimalnom femuru u usporedbi sa standardnom intravenskom analgezijom, te omogućuje ranu mobilizaciju pacijenata, što smanjuje pojavnost duboke venske tromboze i tromboembolijskih komplikacija. S druge strane, neki živčani ogranci koji sudjeluju u inervaciji zgloba kuka nisu zahvaćeni s QLB , što također treba uzeti u obzir. QLB se pokazao kao potencijalna opcija za anesteziju u kirurgiji kuka, no tek se treba dokazati njegova pouzdanost.

Sesamoid bones play an essential role in first metatarsophalangeal (MTP) joint biomechanics, together with other articular surfaces, joint capsule, plantar fascia, ligaments and tendons. They are prone to different acute and chronic injuries, such as acute fracture, stress fractures, chondromalacia, avascular necrosis, bursitis degenerative changes, inflammation etc., all of which clinically manifest as a painful condition and are often diagnosed under a broad term called sesamoiditis. The mechanism of injury is most commonly associated with overuse of the anterior part of the sole of the foot accompanied by excessive dorsiflexion of the great toe. Sesamoiditis presents with pain and localized swelling in the projection of the tibial sesamoid bone, which is affected more frequently than the fibular one. Diagnostic radiology plays a key role in determination of etiology of the disease, as well as in planning of it’s treatment. Typical radiological examination includes weight-bearing dorsoplantar, lateral, oblique medial and oblique lateral radiographs of the foot, together with a direct axial radiograph of sesamoid bones. Computerized tomography is used for distinction of acute fractures and early stage of stress fractures from other pathological conditions. Magnetic resonance imaging allows differentiation between bony pathology and soft tissue conditions. Sesamoiditis management is primarily conservative and it depends on duration and severity of the condition. Orthotic insoles customized according to pedobarographic findings may be useful for solving biomechanical deformities that could have led to development of sesamoiditis. Specific pads placed under the first MTP joint in order to prevent the great toe from dorsiflexion proved to be a very effective conservative treatment option. Surgical treatment is considered if conservative methods fail to provide sufficient management of the condition., Sezamske kosti u području metatarzofalangealnog zgloba nožnog palca (hallux) dio su anatomsko-biomehaničkog kompleksa kojeg čine zglobna tijela, čahura, plantarna fascija, sveze i tetive mišića. U sklopu navedenog komplek- sa sezamske kosti podložne su raznim akutnim i kroničnim oštećenjima u smislu prijeloma, stres prijeloma, hon- dromalacije, avaskularne nekroze, burzitisa, degenerativnih promjena, upala itd., a što se sve klinički očituje kao bolno stanje i sve se podvodi pod široki pojam sesamoiditisa. Mehanizam koji dovodi do sesamoiditisa najčešće je vezan uz prenaprezanje prednjeg dijela stopala praćenog ekscesivnom dorzifleksijom nožnog palca. U kliničkoj sli- ci sesamoiditisa najčešći simptom je bol i lokalizirana oteklina i to u području tibijalne sezamske kosti koja je dale- ko češće zahvaćena u odnosu na fibularnu sezamsku kost. Radiološka dijagnostika je značajna kako u otkrivanju etiologije tako i u planiranju liječenja sesamoiditisa. Standardna radiološka pretraga obuhvaća antero-posteriornu snimku pod opterećenjem stopala, lateralnu snimku, kose snimke te aksijalnu snimku sezamskih kostiju. Komp- juterizirana tomografija pokazala se korisnom za razlikovanje akutnog prijeloma i ranog stadija stres prijeloma sezamske kosti od drugih patologija koje mogu zahvatiti sezamske kosti. MRI omogućuje diferencijaciju između koštanih promjena i promjena na mekom tkivu. Liječenje sezamoiditisa je prvenstveno konzervativno i uvelike ovisno o uznapredovalosti promjena u području cijelog metatarzofalangealnog kompleksa. Ortopedski ulošci nakon pedobarografske analize opterećenja stopala mogu otkloniti biomehaničke deformacije koje su potencijalno pridonijele razvoju sesamoiditisa. Posebni podlošci ispod metatarzofalangealnog zgloba palca u smislu sprečavanja dorzifleksije palca su vrlo korisni i efikasni u konzervativnom liječenju sesamoiditisa. Kirurško liječenje može biti preporučeno nakon neuspjelog konzervativnog liječenja.

Articular cartilage is a hyaline cartilage 2–4 mm thick. It is composed of 95% of dense extracellular matrix (ECM) and 5% of highly specialized cells called chondrocytes. Because of its avascular, aneural and alymphatic state, it has a limited repair potential. Articular cartilages’ main function is to provide smooth, lubricated surface for low friction articulation while minimizing the stress and strains on the matrix. Articular cartilage could be damaged by normal wear and tear or injury and it can cause severe pain, inflammation and some degree of disability. Its management consist of pharmacological (acetaminophen, NSAID, salicylate, selective COX-2 inhibitors or opioids) and non-pharmacological therapies. Non-pharmacological treatment includes physical therapy and decreasing the load in the joint by modifying patient’s habits. A new class of agents (symptomatic or disease modifying osteoarthritic drugs (S/DMOADs) including glucosamine and chondroitin sulfate is receiving wide publicity. At the same time, numerous published reports advising the use of hyaluronic acid injections: viscosupplementation in patients with symptomatic osteoarthritis. Operative treatment includes different surgical debridement and microfracture techniques, osteochondral autograft transfers, osteochondral allograft transplantation, etc. New techniques and concepts are being developed not only to treat damaged or diseased joint cartilage but also to find ways of achieving regeneration to normal cartilage that will give long-lasting improvements and allow patients to return to a fully active lifestyle. Nevertheless, as two stage procedures involving cell culture are expensive and cumbersome, there is an increasing push towards a single stage stem cell treatment. Currently, there are a number of new methods with cartilage repair aim, including autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation (MACI), intra-articular administration of autologous microfragmented fat tissue with Ad-MSCs, etc. In this chapter, we discuss some current treatments and the emerging strategies/techniques employed by researchers and physicians thriving to repair articular cartilage through biological means.

Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease.

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular administration of autologous microfragmented adipose tissue containing adipose- derived mesenchymal stem cells (Ad-MSCs) to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non- randomized, interventional, single-center, open- label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final product containing a derivate of micronized fatty tissue with pericytes and mesenchymal stem cells (Ad-MSCs) into the affected knee(s) was performed in all patients. Patients were assessed for Visual Analogue Scale (VAS), dGEMRIC MRI imaging and immunoglobulin G (IgG) glycans at the baseline, 3, 6 and 12 months after the treatment. T1 relaxation time in dGEMRIC due to infiltration of the anionic, negatively charged contrast Gd- DTPA2− into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC MRI imaging consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of (Ad-MSC) in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycans (GAGs) content in hyaline cartilage, which is in line with observed VAS and clinical results.