Introduction: The infrapatellar fat pad was first described in 1904 by Albert Hoffa. Sometimes disregarded, it is apparent that the infrapatellar fat pad is of importance to knee joint function as fat at this site is only lost in severely emaciated individuals. Also, recent MRI studies have described various pathological changes affecting the fat pad. This study examined the anatomy of the infrapatellar fat pad in relation to knee symptoms and surgical approaches. Materials and Methods: 8 preserved knees were dissected via semicircular parapatellar incisions extending from the tibial tubercle to the superior patellar border and including the quadriceps muscle 13 cm above the superior border of the patella. The synovial membrane of the joint and the ligamentum mucosum were divided and the tibial tubercle was then excised. The resultant tissue complex was removed and the fat pad dissected away from surrounding structures. The appearance, volume and presence of any clefts in the pad were recorded. The cadaveric dissections were then compared to direct observation of the fat pad during total knee replacement, during arthroscopy and on MR imaging. Results: The infrapatellar fat pad was found to be present in all cases. It had a consistent shape consisting of a central mass with medial and lateral extensions. The ligamentum mucosum was attached to the intercondylar notch of the femur in all cases and measured an average of 15.7mm at its base. A horizontal cleft was found in 6 cases and a vertical cleft was found in 7 cases. Both have been previously noted. A tag extended superiorly from the posterior aspect of the fat pad in 7 cases. The volume of the fat pad had quite a large range among individual cadavers (average volume was 24 ml, range: 12–36ml). The intra-individual variation was smaller with an average difference of 4ml (range:2.7ml) between knees. Discussion: The infrapatellar fat pad has been implicated in a wide variety of conditions affecting the knee joint. It has been shown to be involved in arthofibrosis of the knee following surgery, patellar tendonitis, formation of intra-articular fibrous bands, and a site of an ossifying chondroma. It seems that fat pad pathology is usually secondary to other knee joint pathology and primary involvement is rare. The presence of clefts in the fat pad is of importance as a distended cleft may mimic an abnormality and an abnormality in the cleft may be overlooked on imaging of the knee joint. The appearance of the fat pad on direct visualisation in the living person presented a fat pad with a more globular appearance than that seen in the cadaver. The clefts were clearly visualised on MRI. Conclusion: The infrapatellar fat pad is a structure that is consistently present in the knee joint. It consists of a central body with medial and lateral and medical extensions. It usually contains a vertical cleft located superiorly and a horizontal cleft located inferiorly as well as a tag of fat extending superiorly, which forms the roof of the vertical cleft. The infrapatellar fat pad is attached to the intercondylar notch of the femur by the ligamentum mucosum and is firmly anchored to the patella by dense fibrous tissue

Purpose: The study was designed to evaluate the biomechanical and neurohistological properties of the infrapatellar fat especially concerning its potential role in the anterior knee pain syndrome. Methods: Isokinetic knee extension from 120 of flexion to full extension was simulated on 10 human knee cadaver specimens (6 male, 4 female, average age at death 44 years). Joint kinematics was evaluated by ultrasound sensors (CMS 100TM, Zebris, Isny, Germany), and retro-patellar contact pressure was measured using a thin-film resistive ink pressure system (K-ScanTM 4000, Tekscan, Boston). The infrapatellar tissue pressure was analyzed using a closed sensor cell. The patellar contact pressure was measured before and after resection of the infrapatellar fat pad. The distribution of nerve fibres in the infrapatellar fat pad was assed immunohistologically in a second part of the study. Results: Infrapatellar tissue pressure significantly increased during knee extension < 20 and flexion > 100 ranging from 343 (223) mbar at O- to 60 (64) mbar at 60 of flexion. Total resection of the infrapatellar fat pad resulted in a significant decrease in tibial external rotation of 3° in full knee extension (p=0.011), combined with a significant medial translation of the patella between 29 and 69° knee flexion (p=0.017 to 0.028). Retropatellar contact pressure was significantly (p< 0.05) reduced at all flexion angles, at 120° knee flexion more than in full knee extension. Studying all the detectable nerves present in 50 fields (x200 objective) we found an average of 6.4 substance-P- (25%) of a total of 24.7 nerve fibres in the infrapatellar fat pad. There was a significantly (p< 0.01) higher number of substance-P-fibers (24.4 (28%) of 105.7) in the superficial synovial tissue. The number of S-100-fibers was significantly (p< 0.05) higher in the central and lateral part of the fat pad. Conclusions: Based on these results, we conclude that resection of the infrapatellar fat pad could potentially reduce clinical symptoms in the anterior knee pain syndrome, and that, contrary to commonly believed, the infrapatellar fat pad may have a biomechanical function and play a role in the anterior knee pain syndrome

Introduction: Autologous chondrocytes harvested from articular cartilage are being used for the repair of focal cartilage defects. The procedure involves injury to the cartilage and alternative sources of stem cells for use in repair are being explored. Stem cells have been found in many tissue including bone marrow and the infrapa-tellar fat pad. Infrapatellar fat pad derived stem cells present a viable and easily accessible source of stem cells for the repair of cartilage defects and tissue engineering applications. Hypoxia has been shown to improve chondrogenesis in stem cells derived from the bone marrow. We explore the hypothesis that this effect would also apply to stem cells derived from the infrapatellar fat pad. Materials and methods: Cell aggregates from early passage stem cells isolated from the infrapatellar fat pad were placed in chondrogenic media for 14 days either in a normoxic (20% oxygen) or hypoxic (5% oxygen) environment. Gene expression analysis, DNA and glycosoaminoglycan assays and immunohistochemi-cal studies were performed on the aggregates to assess chondrogenesis. Results: Cells grown under hypoxic conditions showed significantly improved chondrogenesis as determined by relatively higher gene expression of proteoglycans, collagens and SOX genes. The cell aggregates also had a higher glycosoaminoglycan content and glycosoamino-glycan content per DNA. Immunohistochemical studies confirm enhanced production of collagen types I and II and aggrecan. Discussion: These findings confirm the previously documented effects of hypoxic culture conditions on stem cells and extend the findings to include infrapatellar fat pad derived stem cells. Our findings suggest that oxygen tension has a role in regulating the function of stem cells as they undergo chondrogenesis. In culture these cells appear to function optimally in an atmosphere of reduced oxygen that more closely approximates documented in vivo oxygen tension. This has important implications in future tissue engineering applications of these cells

Aims: The purpose of the study was to determine the distribution and speciþcation of nerve þbers in the infrapatellar fat pad especially concerning nociceptive substance-P þbres. Methods: The infrapatellar fat pad was taken as a fresh specimen out of 21 patients (4 male, 17 female, mean age 69 years) during total knee arthroplasty. It was dissected in þve deþned parts, þxed and embedded in parafþn. Immunohistochemical techniques using antibodies against S-100 protein and substance-P were employed to determine and specify the nerve þbres. Results: Studying all the detectable nerves present in 50 þelds (x200 objective) we found an average of 6,4 substance-P- (25%) of a total of 24,7 nerve þbres in the infrapatellar fat pad. There was a significantly (p< 0,01) higher number of substance-P-þbers (24,4 (28%) of 105,7) in the surfacing synovial tissue. The number of S-100-þbers was signiþcantly (p< 0,05) higher in the central and lateral part of the fat pad. Conclusions: The occurance and distribution of nerve þbres in the infrapatellar fat pad suggests a nociceptive function. A neurohistological role in the anterior knee pain syndrome is assumed

Aims: This biomechanical study was performed to evaluate the consequences of a total infrapatellar fat pad resection on knee kinematics and patellar contact pressure. Methods: Knee motion between 120∞ of flexion and full extension was performed in a knee kinemator on 10 fresh frozen knee specimens (6 male, 4 female, average age 44 years). The joint kinematics was evaluated by ultrasound sensors (Zebris-system), the patellar contact pressure was measured using a thin-film resistive ink pressure system (Tekscan). All data were taken before and after resection of the infrapatellar fat pad and statistically analyzed. Results: A total resection of the infrapatellar fat pad resulted in a significant (p< 0,05) decrease of the tibial external rotation in knee extension combined with a significant (p< 0,05) medial translation of the patella. The patellar contact pressure was significantly (p< 0,05) reduced, in knee flexion more than in knee extension. Conclusions: We conclude that a resection of the infrapatellar fat pad might reduce clinical symptoms in the anterior knee pain syndrome. A biomechanical function of the infrapatellar fat is suspected

There is an ever-increasing clinical need for the regeneration and replacement of tissue to replace soft tissue lost due to trauma, disease and cosmetic surgery. A potential alternative to the current treatment modalities is the use of tissue engineering applications using mesenchymal stem cells that have been identified in many tissue including the infrapatellar fat pad. In this study, stem cells isolated from the infrapatellar fat pad were characterised to ascertain their origin, and allowed to undergo adipogenic differentiation to confirm multilineage differentiation potential. The infrapatellar fat pad was obtained from total knee replacement for osteoarthritis. Cells were isolated and expanded in monolayer culture. Cells at passage 2 stained strongly for CD13, CD29, CD44, CD90 and CD105 (mesenchymal stem cell markers). The cells stained poorly for LNGFR and STRO1 (markers for freshly isolated bone marrow derived stem cells), and sparsely for 3G5 (pericyte marker). Staining for CD34 (haematopoetic marker) and CD56 (neural and myogenic lineage marker) was negative. For adipogenic differentiation, cells were cultured in adipogenic inducing medium consisting of basic medium with 10ug/ml insulin, 1uM dexamthasone, 100uM indomethacin and 500uM 3-isobutyl-1-methyl xanthine. By day 16, many cells had lipid vacuoles occupying most of the cytoplasm. On gene expression analyses, the cells cultured under adipogenic conditions had almost a 1,000 fold increase in expression of peroxisome proliferator-activated receptor gamma-2 (PPAR gamma-2) and 1,000,000 fold increase in expression of lipoprotein lipase (LPL). Oil red O staining confirmed the adipogenic nature of the observed vacuoles and showed failure of staining in control cells. Our results show that the human infrapatellar fat pad is a viable potential autogeneic source for mesenchymal stem cells capable of adipogenic differentiation as well as previously documented ostegenic and chondrogenic differentiation. This cell source has potential use in tissue engineering applications

1. Three patients are reported in whom a sudden acute internal derangement of the knee was caused by torsion of a pedunculated portion of the infrapatellar fat pad. 2. The symptoms and signs are described. 3. The pathological changes and the pathogenesis are discussed

There is an ever-increasing clinical need for the regeneration and replacement of tissue to replace soft tissue lost due to trauma, disease and cosmetic surgery. A potential alternative to the current treatment modalities is the use of tissue engineering applications using mesenchymal stem cells that have been identified in many tissue including the infrapatellar fat pad. In this study, stem cells isolated from the infrapatellar fat pad were characterised to ascertain their origin, and allowed to undergo adipogenic differentiation to confirm multilineage differentiation potential. The infrapatellar fat pad was obtained from total knee replacement for osteoarthritis. Cells were isolated and expanded in monolayer culture. Cells at passage 2 stained strongly for CD13, CD29, CD44, CD90 and CD105 (mesenchymal stem cell markers). The cells stained poorly for LNGFR and STRO1 (markers for freshly isolated bone marrow derived stem cells), and sparsely for 3G5 (pericyte marker). Staining for CD34 (haematopoetic marker) and CD56 (neural and myogenic lineage marker) was negative. {BR}For adipogenic differentiation, cells were cultured in adipogenic inducing medium consisting of basic medium with 10ug/ml insulin, 1uM dexamthasone, 100uM indomethacin and 500uM 3-isobutyl-1-methyl xanthine. By day 16, many cells had lipid vacuoles occupying most of the cytoplasm. On gene expression analyses, the cells cultured under adipogenic conditions had almost a 1,000 fold increase in expression of peroxisome proliferator-activated receptor gamma-2 (PPAR gamma-2) and 1,000,000 fold increase in expression of lipoprotein lipase (LPL). Oil red O staining confirmed the adipogenic nature of the observed vacuoles and showed failure of staining in control cells. Our results show that the human infrapatellar fat pad is a viable potential autogeneic source for mesenchymal stem cells capable of adipogenic differentiation as well as previously documented ostegenic and chondrogenic differentiation. This cell source has potential use in tissue engineering applications

Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice. After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissue-engineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects

Introduction: Anterior knee pain is a very common presenting symptom. Fat pad syndrome is an uncommon and a difficult condition to manage. The diagnosis is usually reached after a period of physiotherapy and investigation to rule out the more common aetiologies of anterior knee pain. Patients & Methods: All patients who underwent excision of the infrapatellar fat pad following a diagnosis of Fat pad syndrome are included. Each patient was evaluated to exclude patellofemoral problems and intraarticular pathologies as the cause of anterior knee pain. Each patient underwent MR imaging and all the excised specimens were sent for histological analysis. Results: The MR imaging provided with the provisional diagnosis in all patients. All the specimens were examined by a single senior histopathologist to correlate with the provisional diagnosis. The histology confirmed Hoffa’s syndrome in 5 patients and in the remaining 15 patients a spectrum of rare diagnoses as suspected by Magnetic Resonance imaging. The more notable conditions were two synovial sarcomas, three haemangiomas and a Giant cell tumour of the tendon sheath. All patients were treated successfully with complete excision. No recurrences were recorded at the end of 3 year follow-up and all patients were symptom free. Conclusion: The work up of a patient with suspected infrapatellar fat pad syndrome must include MR imaging and the exact underlying pathology should be confirmed with histological analysis of the excised fat pad as the rare causes include soft tissue malignancy

Introduction. With an ongoing increase in total knee arthroplasty (TKA) procedural volume, there is an increased demand to improve surgical techniques to achieve ideal outcomes. Considerations of how to improve post-operative outcomes have included preservation of the infrapatellar fat pad (IPFP). Although this structure is commonly resected during TKA procedures, there is inconsistency in the literature and among surgeons regarding whether resection or preservation of the IPFP should be achieved. Additionally, information about how surgical handling of the IPFP influences outcomes is variable. Therefore, the purpose of this systematic review was to evaluate the influence of IPFP resection and preservation on post-operative flexion, pain, Insall-Salvati Ratio (ISR), Knee Society Score (KSS), patellar tendon length (PTL), and satisfaction in primary TKA. Methods. A systematic literature search was performed to retrieve all reports that evaluated IPFP resection or preservation during total knee arthroplasty (TKA). The following databases were queried: PubMed, EBSCO host, and SCOPUS, resulting in 488 unique reports. Two reviewers independently reviewed the studies for eligibility based on pre-established inclusion and exclusion criteria. A total of 11 studies were identified for final analysis. Patient demographics, type of surgical intervention, follow-up duration, and clinical outcome measures were collected and further analyzed. This systematic review reported on 11,996 total cases. Complete resection was implemented in 3,723 cases (31%), partial resection in 5,458 cases (45.5%), and preservation of the IPFP occurred in 2,815 cases (23.5%). Clinical outcome measures included patellar tendon length (PTL) (5 studies), knee flexion (4 studies), pain (6 studies), Knee Society Score (KSS) (3 studies), Insall-Salvati Ratio (ISR) (3 studies), and patient satisfaction (1 study). Results. There were no differences found following IPFP resection for patient satisfaction (p=0.92), ISR (all p-values >0.05), and KSS (all p-values >0.05). Mixed evidence was found for patellar tendon length, pain, and knee flexion following IPFP resection vs. preservation. Conclusion. Given the current literature and available data, there were several clinical outcome measures that indicated better patient results with preservation of IPFP during primary TKA in comparison to the resection of IPFP. Specifically, resection resulted in inferior outcomes for patellar tendon length, knee flexion, and pain measurements. However, more extensive research is needed to better determine that preservation is the superior surgical decision. This includes a need for more randomized controlled trials (RCTs). Future studies should focus on conditions in which preservation or resection of IPFP would be best indicated during TKA in order to establish guidelines for best surgical outcomes in those patients. For any figures or tables, please contact authors directly

Introduction: In this study infrapatellar fat pad (IPFP) derived stem cells were expanded with and without Fibroblast Growth Factor-2 (FGF-2) supplementation and were compared with regards to their ability to proliferate and differentiate into chondrocytes. Materials and Methods: Cells were isolated from the IPFP tissue and expanded in monolayer culture with and without rhFGF-2 supplementation (final concentration 10ng/ ml). Cell aggregates were placed in chondrogenic media for two weeks. Gene expression studies were carried out using quantitative real time PCR. Immunohistochemical labelling was performed with antibody localisation determined by an immunoperoxidase procedure. The pellets were also weighed and digested in papain for DNA and glycosoaminoglycan (GAG) analysis. Results: Cells expanded in FGF-2 supplemented media were smaller and proliferated more rapidly. The FGF-2 supplemented cell aggregates also showed 100 times higher expression of collagen type II (COL2A1). Immunohistochemical studies showed that pellets made from FGF-2 treated cells stained more strongly for collagen II and more weakly for collagen I. Pellets made with FGF-2 treated cells were larger, continued with enhanced proliferation and contained more proteoglycan. Conclusion: Our findings show enhanced proliferation and chondrogenic differentiation in IPFP derived stem cells expanded in FGF-2 supplemented media

Although chondrocytes have been used for autologous implantation in defects of articular cartilage, limited availability and donor-site morbidity have led to the search for alternative cell sources. Mesenchymal stem cells from various sources represent one option. The infrapatellar fat-pad is a promising source. Advantages include low morbidity, ease of harvest and ex-vivo evidence of chondrogenesis. Expansion of MSCs from human fat-pad in FGF-2 has been shown to enhance chondrogenesis. To further elucidate this process, we assessed the role of TGF-?3, FGF-2 and oxygen tension on growth kinetics of these cells during expansion.

The purpose of this study in to investigate the role of infrapatellar fat pad on primary total knee arthroplasty. We evaluated 100 patients who had been undergone TKA from August 2002 to July 2003, with open box posterior substituting femoral component implant (Scorpio PS Knee. ™. ). The study was performed prospectively and randomly allocated. We divided two groups. Group 1 (50 knees) was preserved infrapatellar fat pad and repaired fad at wound closure. Group 2 (50 knees) was excised infrapatellar fat pad as possible and repaired only joint capsule. We analyzed and compared clinical results of Knee Society knee (KS) score, function score, patellar score and Insall-Salvati ratio in both groups. The complications of each group were evaluated. Patients were followed up for mean 40 months(17~52 months). Mean KS score was 91.9 (91.94±5.58) in Group 1 and 90.9(90.92±6.38) in Group 2. Mean function score was 81.6(81.64±13.18) in Group 1 and 83.7(83.79±17.71) in Group 2. Mean patellar score was 29.9(29.89±9.10) in Group 1 and 27.9(27.90±1.80) in Group 2. And mean patellar height as Insall-Salvati ratio was 1.19(1.19±0.17) in Group 1 and 1.23(1.23±0.11) in Group 2. The differences between the Group 1 and Group 2 in all of index were statistically insignificant. In complications, 2 cases of recurrent hemarthrosis were observed in Group 1 patients. We concluded The difference of clinical outcomes whether infrapatellar fat pad was excised or not were statistically insignificant. However, preservation of infrapatellar fat pad on open boxed PS TKA showed unique complications such as recurrent hemarthrosis which might be caused by fat pad adhesion to intercondylar notch. We propose that infrapatellar fat pad on primary PS TKA with open box design would like to be excised for prevention of unique complications

Articular cartilage is often damaged, and its treatment is usually performed by surgical operation. Today, tissue engineering offers an alternative treatment option for injuries or diseases with increasing importance. Infrapatellar fat pad (IPFP) is a densely vascularized and innervated extra synovial tissue that fills the anterior knee compartment. Adipose-derived stem cells from infrapatellar fat pad (IPFP-ASCs) have multipotency means that they can differentiate into connective tissue cells and have age-independent differentiation capacity as compared to other stem cells. In this study, the osteochondral tissue construct was designed with different inner pattern due to original osteochondral tissue structure and fabrication of it was carried out by 3D printing. For this purpose, alginate (3% w/v) and carboxymethylcellulose (CMC) (9%w /v) were used as bioink. Also, IPFP-ASCs were isolated with enzymatic degradation. Osteogenic and chondrogenic differentiation of IPFP-ASCs were investigated with Alizarin Red and Alcian Blue staining, respectively. IPFP-ASCs-laden osteochondral graft differentiation will be induced by controlled release of growth factor BMP-2 and TGF-β. Before this step, nanocapsules formation with double emission technique with model protein BSA was carried out with different concentration of PCL (5%,10% and 20%). The morphology and structure of the nanocapsules were determined with scanning electron microscopy (SEM). Also, we successfully designed and printed alginate and CMC based scaffold with 20 layers. Chondrogenic and osteogenic differentiation of IPFP-ASCs with suitable culture conditions was obtained. The isolation of IPFP-ASCs, formation of the nanocapsules, and 3D printing of osteochondral graft were carried out successfully

Introduction. Mesenchymal stem cells (MSC) are an attractive cell population for regeneration of mesenchymal tissue such as bone and cartilage. Various studies have demonstrated the repair capacity of MSCs and even their usefulness in treating critical size defects. Much of the work conducted on adult stem cells has focused on MSCs found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. The aim of the present study is to evaluate the differentiation capability of adipose-tissue derived stem cells (ASC) extracted from the infrapatellar fat pad. Materials and Methods. Human infrapatellar fat pad tissue was obtained from patients undergoing total joint replacement for osteoarthritis with full ethical consent. A multipotent progenitor cell population was derived after collagenase digestion from the adipose tissue. The ASCs were induced to differentiate towards adipogenic, chondrogenic, and osteogenic lineages for 21 days both in normoxic and hypoxic cell culture conditions. The differentiation and multilineage potential was assessed according to cell morphology and in vitro detection of tissue-specific differentiation molecules. Results. After 3 weeks in culture the staining for oil-red-o, alcian bue, and alizarin-red confirmed the differentiation capability of ASC's to adipogenic, chondrogenic, and osteogenic lineages, respectively. The hypoxic cell culture condition was found to support the ASCs' chondrogenic differentiation capability and subsequently enhanced the proteoglycan release from the cells. Fluorescence-activated cell sorting (FACS) confirmed the presence of stromal precursor cell marker STRO-1 in the ASC population. Discussion. Subcutaneous adipose tissue is particularly attractive reservoir for progenitor cells because it is easily accessible, rather abundant, and self-replenishing. The results of this study demonstrate that ASCs can be derived from infrapatellar fat pad and that they have potential for musculoskeletal tissue repair and regeneration. Further studies are underway to evaluate how to adopt a biomaterial to deliver these cells into the defect area to facilitate the healing response

Achieving deep flexion of knee after total knee arthroplasty (TKA) is particularly desirable in some Asian and Middle Eastern who have daily or religious customs typically use full knee flexion. After TKA, some patients complained about anterior knee pain during deep knee flexion. We evaluated the efficacy of arthroscopic fat pad resection in a series of patients suffering from anterior knee pain associated with high flexion achievement after TKA. The efficacy of fat pad resection via arthroscopy for treating anterior knee pain associated with high flexion angle (average = 133.1°) was evaluated in eight knees of eight patients among 207 knees performed between 1996 and 1999. The mean age of patients was 71.1 years when the primary TKA was performed. All implatants were posterior stabilized type (IB-II, Nexgen PS and LPS). The symptom of anterior knee pain during deep knee flexion developed within one year after TKA in all cases. In addition to pain in eight knees, two patients have crepitation as the knee was flexed and extended and three patients had hydrarthrosis. Impingement and fibrosis of fat pad were confirmed, and fibrous structures were removed by arthroscopy. Before arthroscopy, the symptom obviously subsided after injection of local anesthesia into infrapatellar fat pad. Patellar clunk syndrome is also soft tissue impingement and suprapatellar fibrous nodule becomes entrapped intercondylar notch on the femoral component during knee flexion. On this point, these cases does not cause by patellar clunk syndrome. After fat pad resection, the symptom disappeared, and keeps symptom-free after a mean follow-up of six years five months in all cases. Any complications following fat pad resection, such as patella baja and necrosis, were not experienced. Those cases achieving higher flexion angle tended to experience severe pain and shorter time interval between TKA and arthroscopic surgery, suggesting impingement of the infrapatellar fat pad is closely related to deep flexion after TKA. These results demonstrate that the anterior knee pain due to repetitive infrapatellar fat pad impingement is one of the complications during deep knee flexion after TKA, and the arthroscopic fat pad resection is useful to relief the anterior knee pain. Because of our experience with patients encountering anterior knee pain, we have begun to remove 70 to 80% of the fat pad during the primary TKA procedure since 1999, and until today, none developed anterior knee pain thought to be associated with fat pad impingement, patellar baja nor patellar necrosis. We suggest that fat pad resection is necessary to prevent the anterior knee pain due to fat pad impingement during deep flexion in TKA

The incidence of osteoarthritis (OA) is increasing in our younger population. OA development early in life is often related to cartilage damage, caused by (sport) injury or trauma. Detection of early knee OA is therefore crucial to target early treatment. However, early markers for OA prognosis or diagnosis are lacking. Hoffa's fat pad (HFP) is an emerging source for knee biomarkers, as it is easily accessible and shows important interaction with the homeostasis of the knee. In this study, we used Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) as a first approach. MALDI-MSI allows the study of tissue-specific molecular distributions. Therefore, we used MALDI-MSI to analyze the lipid profiles in the HFP of three patients with OA and three patients undergoing cartilage regenerative treatment. We demonstrate that the lipid profile of patients with OA is different from patients with cartilage defects.

HFP of each patient were snap frozen directly after surgical resection and cryosectioned at 15 μm. Each slide was sublimed with Norharmane matrix and analyzed by MALDI-MSI in positive and negative ion modes at a lateral resolution of 50 μm on a RapifleX Tissue Typer. The difference between patient groups were analyzed using principle component analysis and linear discriminant analysis. Lipid identifications were obtained on an Orbitrap Elite™ Hybrid Ion Trap-Orbitrap Mass Spectrometer in data dependent acquisition mode and analyzed using Lipostar software.

Linear discriminant analysis showed a specific lipid profile for each group (variance 33.94%). Score projections revealed a differential lipid spatial distribution of OA patients compared to cartilage defect patients. Among the lipids that differed significantly, for instance, the m/z 760.59 [M+H]⁺ was associated to osteoarthritis and identified as glycerophospholipid (PC 34:1), a main component of biological membranes. Additionally, the samples were found to be intra-tissue heterogeneous, with molecular profiles found in adipose-, connective- and synovial tissue.

These results suggest that lipid profiles in HFP could be useful for early OA detection. However, intra-tissue heterogeneity in HFP should be recognized when using HFP as a biomarker source.

3D printing and Bioprinting technologies are becoming increasingly popular in surgery to provide a solution for the regeneration of healthy tissues. The aim of our project is the regeneration of articular cartilage via bioprinting means, to manage isolated chondral defects. Chrondrogenic hydrogel (chondrogel: GelMa + TGF-b3 and BMP6) was prepared and sterilised in our lab following our standard protocols. Human adipose-derived mesenchymal stem cells were harvested from the infrapatellar fat pad of patients undergoing total knee joint replacements and incorporated in the hydrogel according to our published protocols. The chondrogenic properties of the chondrogel have been tested (histology, immunohistochemistry, PCR, immunofluorescence, gene analysis and 2. nd. harmonic generation microscopy) in vitro and in an ex-vivo model of human articular defect and compared with standard culture systems where the growth factors are added to the media at repeated intervals. The in-vitro analysis showed that the formation of hyaline cartilage pellet was comparable between the two strategies, with a similar metabolic activity of the cells. These results have been confirmed in the ex-vivo model: hyaline-like cartilage was observed within the chondral defect in both the chondrogel group and the control group after 28 days in culture. The use of bioprinting techniques in vivo requires the ability of stem cells to access growth factors directly in the environment they are in, as opposed to in vitro techniques where these factors are provided externally at recurrent intervals. This study showed the successful strategy of incorporating chondrogenic growth factors for the formation of hyaline-like cartilage in vitro and in an ex-vivo model of chondral loss. The incorporation of chondrogenic growth factors in a hydrogel is a possible strategy for articular cartilage regeneration

From October 2005 to March 2014, we performed 46 arthroscopic surgeries for painful knee after knee arthroplasty. We excluded 16 cases for this study such as, unicompartmental knee arthroplasty, infection, patellar clunk syndrome, patellofemoral synovial hyperplasia, aseptic loosening, and follow-up period after arthroscopic surgery less than 6 months. Thirty cases matched the criteria. They had knee pain longer than 6 months after initial total knee arthroplasty (TKA), they had marked tenderness at medial and/or lateral tibiofemoral joint space, and also they complained walking pain with or without resting pain. Twenty one cases had initial TKA at our institute. In consideration of total number of TKA (n=489) in the period at our institute, incident rate of painful knee after initial TKA was 4.3%. Of 30 cases, 3 cases were male, and 27 cases were female. Types of implant were 4 in cruciate retaining type, 1 in cruciate substituting type, and 25 in posterior stabilized type. Age at the arthroscopy was 72 years old (51–87 years old), and period form initial TKA to pain perception was 18 months(1 – 144 months), and period from initial TKA to arthroscopic surgery was 29 months (6 – 125 months), and follow-up period after arthroscopy was 36 months (6 – 93 months). All arthroscopic debridement were performed through 3 portals, anteromedial, anterolateral, and proximal superomedial portal. Scar tissue impingements more than 5 mm wide were found in 87% of the cases both medial and lateral femorotibial joint spaces. Infrapatellar fat pad were covered with whitish scar tissue in all cases, and the scar tissue were connecting with the scar tissue which found at medial or lateral femorotibial joint spaces. We removed all scar tissue with motorized shaver or punches. At final follow-up, complete pain free in 63%, marked improvement in 3%, half improvement in 20%, slight improvement in 3%, and no change in 10% of the cases. Previously in the literatures, two reasons of the pain after total knee arthroplasty had been reported, patellar clunk syndrome, and patellar synovial hyperplasia. All cases reported this study had marked tenderness at tibiofemoral joint space. It was difficult to explain the tenderness by previously reported pathological mechanisms. We had to find another pathological mechanism to explain the pain of our cases. Painful knee due to scar tissue formation known as “infrapatellar contracture syndrome” after anterior cruciate ligament reconstruction surgery was previously reported. We hypothesized similar scar tissue formation should occur after TKA that caused painful knee. Continuity of the solid scar tissue between infrapatellar fat pad with the scar tissue at tibiofemoral joint space should be the cause of impingement at femorotibial joint even small size of scar tissue. From this study, we have to recognize that painful knee after TKA is not infrequent complication. And, if we could deny infection, and aseptic loosening in painful knee after TKA, arthroscopic debridement was good option to solve the pain. We could expect improvement of the pain more than half in 87% of cases

Abstract. Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties. We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the infrapatellar fat pad using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes

Abstract. Focal articular cartilage defects do not heal and, left untreated, progress to more widespread degenerative changes. A promising new approach for the repair of articular cartilage defects is the application of cell-based regenerative therapies using mesenchymal stromal cells (MSCs). MSCs are however present in a number of tissues and studies suggest that they vary in their proliferation, cell surface characterisation and differentiation. As the phenotypic properties of MSCs vary depending on tissue source, a systematic comparison of the transcriptomic signature would allow a better understanding of these differences between tissues, and allow the identification of markers specific to a MSC source that is best suited for clinical application. Tissue was used from patients undergoing total knee replacement surgery for osteoarthritis following ethical approval and informed consent. MSCs were isolated from bone, cartilage, synovium and infrapatellar fat pad. MSC number and expansion were quantified. Following expansion in culture, MSCs were characterised using flow cytometry with several cell surface markers; the cells from all sources were positive for CD44, CD90 and CD105. Their differentiation potential was assessed through tri-lineage differentiation assays. In addition, bulk mRNA-sequencing was used to determine the transcriptomic signatures. Differentially expressed (DE) genes were predicted. An enrichment analysis focused on the DE genes, against GO and pathway databases (KEGG and Reactome) was performed; protein-protein interaction networks were also inferred (Metascape, Reactome, Cytoscape). Optimal sourcing of MSCs will amplify their cartilage regeneration potential. This is imperative for assessing future therapeutic transplantation to maximise the chance of successful cartilage repair. A better understanding of differences in MSCs from various sources has implications beyond cartilage repair

Two cases of ganglion arising in the alar folds of the infrapatellar fat pad are reported. Both patients had symptoms of internal derangement of the knee, sufficient to justify operation

Anterior knee pain post Total knee Replacement (TKR) has been reported to be as high as 49%. The source is poorly understood; both the peripatellar soft tissues and the infrapatellar fat pad have been implicated. Immunohistochemical studies demonstrate hyperinnervation of the peripatellar soft tissues. In theory circumferential electrocautery denervates the patella. However there is little evidence that this practice translates into improved clinical outcomes. This study aimed to find the effect on clinical outcome, of intraoperative circumpatellar electrocautery in patients undergoing TKR. 200 patients undergoing primary TKR were randomised to circumferential circumpatellar electrocautery or nothing. Patients were assessed for Visual (VAS) for anterior knee pain and Oxford Knee Score (OKS) preoperatively, 3 months, 6 months and 1 year post-procedure. Patients and assessors were blinded to treatment allocation until the end of the study. There were 91 patients in the electrocautery group and 94 controls. The mean VAS improvement from pre-op to one year was 3.8 in both groups. The mean improvement in OKS was 16.6 points in the control and 17.7 in the electrocautery group (p= 0.40). There were no significant differences between the two groups in terms of VAS or OKS at any other time. Although previous studies have conflicting outcomes, to our knowledge this is the first prospective randomised controlled blinded trial of significant power, to evaluate the effect of peripatellar diathermy in TKR. We conclude that denervation electrocautery of the patella makes no difference to the clinical outcomes of TKR

Introduction. Mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. We have previously demonstrated that the infrapatellar synovial fat pad is a rich source of mesenchymal stem cells and these cells are able to undergo chondrogenic differentiation. Although synovial fat pad derived mesenchymal stem cells may represent a heterogenous population, clonal populations derived from the synovial fat pad have not previously been studied. Materials and Methods. Mesenchymal stem cells were isolated from the infrapatellar synovial fat pad of a patient undergoing total knee arthroplasty and expanded in culture. Six clonal populations were also isolated before initial plating using limiting dilution and expanded. The cells from the mixed parent population and the derived clonal populations were characterised for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium for 14 days. Gene expression analyses; glycosoaminoglycan and DNA assays; and immunohistochemical staining were determined to assess chondrogenic responses. Results. Cells from the mixed parent population and the derived clonal populations stained strongly for markers of adult mesenchymal stem cells including CD44, CD90 and CD105, and they were negative for the haematopoietic marker CD34 and for the neural and myogenic marker CD56. Interestingly, a variable number of cells were also positive for the pericyte marker 3G5 both in the mixed parent and clonal populations. The clonal populations exhibited a variable chondrogenic response; one clonal cell population exhibited a significantly greater chondrogenic response when compared with the mixed parent population. Discussion. Pericytes are a candidate stem cell in many tissue and our results show that all six clonal populations derived from the heterogenous synovial fat pad population express the pericyte marker 3G5. The variable chondrogenic responses suggest inherent differences between these populations. The chondrogenic potential of the synovial fat pad could be optimised by the identification of clonal populations with a propensity to differentiate

Introduction: There is an ever-increasing clinical need for the regeneration and replacement of tissue to replace soft tissue lost due to trauma, disease and cosmetic surgery. A potential alternative to the current treatment modalities is the use of tissue engineering applications using mesenchymal stem cells that have been identified in many tissues including the fat pad. In this study, stem cells isolated from the fat pad were characterised and their differentiation potential assessed. Materials and Methods: The infrapatellar fat pad was obtained from total knee replacement for osteoarthritis. Cells were isolated, expanded and stained for a number of stem cell markers. For adipogenic differentiation, cells were cultured in adipogenic inducing medium (10ug/ml insulin, 1uM dexamthasone, 100uM indomethacin and 500uM 3-isobutyl-1-methyl xanthine). Gene expression analyses and Oil red O staining was performed to assess adipogenesis. Results: Cells at passage 2 stained strongly for CD13, CD29, CD44, CD90 and CD105 (mesenchymal stem cell markers). The cells stained sparsely for 3G5 (peri-cyte marker). On gene expression analyses, the cells cultured under adipogenic conditions had almost a 1,000 fold increase in expression of peroxisome proliferator-activated receptor gamma-2 (PPAR gamma-2) and 1,000,000 fold increase in expression of lipoprotein lipase (LPL). Oil red O staining revealed triglyceride accumulation within typical adipogenic morphology, confirming the adipogenic nature of the observed vacuoles, and showed failure of staining in control cells. Discussion: Fat pad derived stem cells expressed a cell surface epitope profile of mesenchymal stem cells, and exhibited the potential to undergo adipogenic differentiation. Our results show that the human fat pad is a viable potential autogeneic source for mesenchymal stem cells capable of adipogenic differentiation as well as previously documented ostegenic and chondrogenic differentiation. This cell source has potential use in tissue engineering applications

Introduction. Mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. We have previously demonstrated that the infrapatellar synovial fat pad is a rich source of mesenchymal stem cells and these cells are able to undergo chondrogenic differentiation. Although synovial fat pad derived mesenchymal stem cells may represent a heterogenous population, clonal populations derived from the synovial fat pad have not previously been studied. Materials and Methods. Mesenchymal stem cells were isolated from the infrapatellar synovial fat pad of a patient undergoing total knee arthroplasty and expanded in culture. Six clonal populations were also isolated before initial plating using limiting dilution and expanded. The cells from the mixed parent population and the derived clonal populations were characterised for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium for 14 days. Gene expression analyses; glycosoaminoglycan and DNA assays; and immunohistochemical staining were determined to assess chondrogenic responses. Results. Cells from the mixed parent population and the derived clonal populations stained strongly for markers of adult mesenchymal stem cells including CD44, CD90 and CD105, and they were negative for the haematopoietic marker CD34 and for the neural and myogenic marker CD56. Interestingly, a variable number of cells were also positive for the pericyte marker 3G5 both in the mixed parent and clonal populations. The clonal populations exhibited a variable chondrogenic response; one clonal cell population exhibited a significantly greater chondrogenic response when compared with the mixed parent population. Discussion. Pericytes are a candidate stem cell in many tissue and our results show that all six clonal populations derived from the heterogenous synovial fat pad population express the pericyte marker 3G5. The variable chondrogenic responses suggest inherent differences between these populations. The chondrogenic potential of the synovial fat pad could be optimised by the identification of clonal populations with a propensity to differentiate down particular differentiation pathways, and this has implications on the future tissue engineering applications of these cells for cartilage repair

Summary. The donor-matched comparison between mesenchymal stem cells from knee infrapatellar and subcutaneous adipose tissue revealed their preferential commitment towards the chondrogenic and osteogenic lineage, respectively. These peculiarities could be relevant for the development of successful bone and cartilage cell-based applications. Introduction. Mesenchymal stem cells (MSCs) have been proposed in bone and cartilage tissue engineering applications as an alternative to terminally differentiated cells. In the present study we characterised and performed a donor-matched comparison between MSCs resident within the infrapatellar fat pad (IFP-MSCs) and the knee subcutaneous adipose tissue (ASCs) of osteoarthritic patients. These two fat depots, indeed, can be considered appealing candidates for orthopaedic cell-based therapies since they are highly accessible during knee surgery. Materials and Methods. IFP-MSCs and ASCs were obtained from 25 osteoarthritic patients undergoing total knee replacement. Undifferentiated cells were compared for their clonogenic ability and surface markers expression. Adipogenic, osteogenic and chondrogenic differentiative potentials were evaluated after IFP-MSCs and ASCs induction towards the various lineages by means of histological, biochemical and gene expression analysis of characteristic markers. Results. We found that undifferentiated IFP-MSCs and ASCs displayed a high clonogenic ability and the typical immunophenotype of MSCs (CD13. +. /CD29. +. /CD44. +. /CD73. +. /CD90. +. /CD105. +. /CD166. +. /CD31. −. /CD45. −. ), without any difference in terms of surface markers expression between these two cell populations. When both cell types were cultured in adequate adipo-, osteo- and chondro- differentiative media, IFP-MSCs and ASCs showed similar adipogenic potential, though undifferentiated ASCs had superior LEP expression compared to undifferentiated IFP-MSCs (p<0.01). ASCs showed a higher response to osteogenic induction in comparison with IFP-MSCs as demonstrated by significantly higher levels of calcified matrix deposition (p<0.05) and alkaline phosphatase activity (p<0.05). After 14 days of chondrogenic induction of cells cultured in pellets, we observed greater amounts of glycosaminoglycans (p<0.01) in IFP-MSCs pellets compared to ASCs pellets. Chondrogenic differentiation of IFP-MSCs showed also a superior gene expression of ACAN (p<0.001), SOX9, COMP (p<0.001) and COL2A1 (p<0.05) compared to ASCs. Furthermore, IFP-MSCs showed significantly lower levels of COL10A1 (p<0.05) and COL1A1 (p<0.01) and lower alkaline phosphatase release (p<0.05) compared to ASCs, supporting the hypothesis of a superior chondrogenic commitment of IFP-MSCs. Discussion/Conclusion. The observed dissimilarities between IFP-MSCs and ASCs suggest that despite similar features at the undifferentiated state, MSCs deriving from different anatomical sites within the same joint can display a specific commitment. The peculiar commitment of IFP-MSCs and ASCs towards the chondrogenic and osteogenic lineage suggests that they may be preferentially used for cartilage and bone applications, respectively

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Aims

This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA).

Aims

Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

Objectives

The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo.

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells.

Cite this article: Bone Joint Res 2020;9(12):857–869.

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Aims

The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice.

Aims

Multimodal infiltration of local anaesthetic provides effective control of pain in patients undergoing total knee arthroplasty (TKA). There is little information about the added benefits of posterior capsular infiltration (PCI) using different combinations of local anaesthetic agents. Our aim was to investigate the effectiveness of the control of pain using multimodal infiltration with and without infiltration of the posterior capsule of the knee.

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon.

Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1β than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1β was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-β1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1β had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process.

Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament.

Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired t-test, p = 0.002). There was a significant reduction of mid-substance signal six months after the minimal debridement technique (paired t-test, p = 0.00007). No statistically significant differences were found in tunnel placement, incidence of Cyclops lesions, blood loss, IKDC scores, range of movement or Lachman test between the two groups.

We evaluated the clinical results and complications after extra-articular resection of the distal femur and/or proximal tibia and reconstruction with a tumour endoprosthesis (MUTARS) in 59 patients (mean age 33 years (11 to 74)) with malignant bone or soft-tissue tumours. According to a Kaplan–Meier analysis, limb survival was 76% (95% confidence interval (CI) 64.1 to 88.5) after a mean follow-up of 4.7 years (one month to 17 years). Peri-prosthetic infection was the most common indication for subsequent amputation (eight patients). Survival of the prosthesis without revision was 48% (95% CI 34.8 to 62.0) at two years and 25% (95% CI 11.1 to 39.9) at five years post-operatively. Failure of the prosthesis was due to deep infection in 22 patients (37%), aseptic loosening in ten patients (17%), and peri-prosthetic fracture in six patients (10%). Wear of the bearings made a minor revision necessary in 12 patients (20%). The mean Musculoskeletal Tumor Society score was 23 (10 to 29). An extensor lag > 10° was noted in ten patients (17%).

These results suggest that limb salvage after extra-articular resection with a tumour prosthesis can achieve good functional results in most patients, although the rates of complications and subsequent amputation are higher than in patients treated with intra-articular resection.

Cite this article: Bone Joint J 2013;95-B:1425–31.

The August 2012 Knee Roundup³⁶⁰ looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy.

We retrospectively reviewed the records of 1150 computer-assisted total knee replacements and analysed the clinical and radiological outcomes of 45 knees that had arthritis with a pre-operative recurvatum deformity. The mean pre-operative hyperextension deformity of 11° (6° to 15°), as measured by navigation at the start of the operation, improved to a mean flexion deformity of 3.1° (0° to 7°) post-operatively. A total of 41 knees (91%) were managed using inserts ≤ 12.5 mm thick, and none had mediolateral laxity > 2 mm from a mechanical axis of 0° at the end of the surgery. At a mean follow-up of 26.4 months (13 to 48) there was significant improvement in the mean Knee Society, Oxford knee and Western Ontario and McMaster Universities Osteoarthritis Index scores compared with the pre-operative values. The mean knee flexion improved from 105° (80° to 125°) pre-operatively to 131° (120° to 145°), and none of the limbs had recurrent recurvatum.

These early results show that total knee replacement using computer navigation and an algorithmic approach for arthritic knees with a recurvatum deformity can give excellent radiological and functional outcomes without recurrent deformity.

The efficacy of circumpatellar electrocautery in reducing the incidence of post-operative anterior knee pain is unknown. We conducted a single-centre, outcome-assessor and patient-blinded, parallel-group, randomised, controlled trial to compare circumpatellar electrocautery with no electrocautery in total knee replacement in the absence of patellar resurfacing. Patients requiring knee replacement for primary osteoarthritis were randomly assigned circumpatellar electrocautery (intervention group) or no electrocautery (control group). The primary outcome measure was the incidence of anterior knee pain. A secondary measure was the standardised clinical and patient-reported outcomes determined by the American Knee Society scores and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. A total of 131 knees received circumpatellar electrocautery and 131 had no electrocautery.

The overall incidence of anterior knee pain at follow-up at one year was 26% (20% to 31%), with 19% (12% to 26%) in the intervention group and 32% (24% to 40%) in the control group (p = 0.02). The relative risk reduction from electrocautery was 40% (9% to 61%) and the number needed to treat was 7.7 (4.3 to 41.4). The intervention group had a better mean total WOMAC score at follow-up at one year compared with the control group (16.3 (0 to 77.7) versus 21.6 (0 to 76.7), p = 0.04). The mean post-operative American Knee Society knee scores and function scores were similar in the intervention and control groups (knee score: 92.4 (55 to 100) versus 90.4 (51 to 100), respectively (p = 0.14); function score: 86.5 (15 to 100) versus 84.5 (30 to 100), respectively (p = 0.49)).

Our study suggests that in the absence of patellar resurfacing electrocautery around the margin of the patella improves the outcome of total knee replacement.

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with β-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)₂D₃, a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced.

Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.

We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon in vitro. Infiltrative fibroblasts were isolated from the patellar tendons of rabbits six weeks after an in situ freeze-thaw treatment which killed the intrinsic fibroblasts. These intrinsic cells were also isolated from the patellar tendons of rabbits which had not been so treated.

Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of α5β1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.