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

The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation. Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice. Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue. TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation

The avascular nature of articular cartilage relies on diffusion pathways to obtain essential nutrients and molecules for cellular activity. Understanding these transport pathways is essential to maintaining and improving the health of articular cartilage and ultimately synovial joints. Several studies have shown that joint articulation is associated with fluid and solute uptake although it remains unclear what role sliding motion independently plays. This study investigates the role of sliding with a non-stationary contact area on the uptake of small molecular weight tracers into articular cartilage. Ten-millimeter diameter cartilage-bone plugs were obtained from porcine knee joints and sealed into purpose made diffusion chambers. The chambers were designed to eliminate diffusion from the radial edge and only allow diffusion through the articular surface. The bone side of the chamber was filled with PBS to maintain tissue hydration while the cartilage side was filled with 0.01mg/ml fluorescein sodium salt (FNa) prepared using PBS. Sliding loads with a non-stationary contact area were applied across the articular surface by a custom apparatus using a 4.5 mm diameter spherical indenter. A moving contact area was chosen to represent physiological joint motions. Reciprocal sliding was maintained at a rate of 5 mm/s for 2 and 4 hours. Control samples were subject to passive diffusion for 0, 4, and 88 hours. After diffusion tests, samples were snap frozen and 20 µm cross-sectional cuts were taken perpendicular to the sliding direction. Samples were imaged using a Zeiss AxioImager M2 epifluorescent microscope under 5× magnification with a filter for FNa. Intensity profiles were mapped from the articular surface to the subchondral bone. Unloaded control samples demonstrated minimal solute uptake at 4 hours penetrating less than 5% of the total cartilage depth. By 88 hours solute penetration had reached the subchondral bone although there was minimal accumulation within the cartilage matrix indicated by the relatively low intensity profile values. Samples that had been subjected to reciprocal sliding demonstrated accelerated penetration and solute accumulation compared to unloaded samples. After 1 hour of reciprocal sliding, the solute had reached 40% of the cartilage depth, this increased to approximately 80% at 4 hours, with much higher intensities compared to unloaded controls. Sliding motion plays an important role in the uptake of solutes into the cartilage matrix. Maintaining joint motion both post injury and in the arthritic process is a critical component of cartilage nutrition. Samples that had been subject to reciprocal sliding demonstrated accelerated solute penetration and accumulation in the cartilage matrix, exceeding steady state concentrations achieved by passive diffusion

The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture. Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy. Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP. Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects

Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and mechanical strength when compared to normal cartilage. The phenotype of cartilage derived from MSCs has been reported to be influenced by the microenvironmental biophysical cues, such as the surface topography and substrate stiffness. In this study, the effect of nano-topographic surfaces to direct MSC chondrogenic differentiation to chondrocytes of different phenotypes was investigated, and the application of these pre-differentiated cells for cartilage repair was explored. Specific nano-topographic patterns on the polymeric substrate were generated by nano-thermal imprinting on the PCL, PGA and PLA surfaces respectively. Human bone marrow MSCs seeded on these surfaces were subjected to chondrogenic differentiation and the phenotypic outcome of the differentiated cells was analyzed by real time PCR, matrix quantification and immunohistological staining. The influence of substrate stiffness of the nano-topographic patterns on MSC chondrogenesis was further evaluated. The ability of these pre-differentiated MSCs on different nano-topographic surfaces to form zonal cartilage was verified in in vitro 3D hydrogel culture. These pre-differentiated cells were then implanted as bilayered hydrogel constructs composed of superficial zone-like chondro-progenitors overlaying the middle/deep zone-like chondro-progenitors, was compared to undifferentiated MSCs and non-specifically pre-differentiated MSCs in a osteochondral defect rabbit model. Nano-topographical patterns triggered MSC morphology and cytoskeletal structure changes, and cellular aggregation resulting in specific chondrogenic differentiation outcomes. MSC chondrogenesis on nano-pillar topography facilitated robust hyaline-like cartilage formation, while MSCs on nano-grill topography were induced to form fibro/superficial zone cartilage-like tissue. These phenotypic outcomes were further diversified and controlled by manipulation of the material stiffness. Hyaline cartilage with middle/deep zone cartilage characteristics was derived on softer nano-pillar surfaces, and superficial zone-like cartilage resulted on softer nano-grill surfaces. MSCs on stiffer nano-pillar and stiffer nano-grill resulted in mixed fibro/hyaline/hypertrophic cartilage and non-cartilage tissue, respectively. Further, the nano-topography pre-differentiated cells possessed phenotypic memory, forming phenotypically distinct cartilage in subsequent 3D hydrogel culture. Lastly, implantation of the bilayered hydrogel construct of superficial zone-like chondro-progenitors and middle/deep zone-like chondro-progenitors resulted in regeneration of phenotypically better cartilage tissue with higher mechanical function. Our results demonstrate the potential of nano-topographic cues, coupled with substrate stiffness, in guiding the differentiation of MSCs to chondrocytes of a specific phenotype. Implantation of these chondrocytes in a bilayered hydrogel construct yielded cartilage with more normal architecture and mechanical function. Our approach provides a potential translatable strategy for improved articular cartilage regeneration using MSCs

Acetabular reconstruction with impaction bone grafting and a cemented polyethylene aims to reconstitute the bone stock in hip revision. This is an effective but expensive, resource intensive and time consuming technique. Most surgeons remove the articular cartilage from the femoral head allograft. The aim of this study is to reproduce the results using the whole femoral head with the articular cartilage for acetabular impaction grafting. 38 acetabular revisions using impacted morselised bone graft retaining the articular cartilage and a cemented cup were studied retrospectively. The operations were performed by the senior author in Wrightington Hospital, UK with a posterior hip approach. The mean follow up was 4.1 years (range, 1–10 years). Clinical and radiological assessment was made using the Oxford hip score, Hodgkinson's criteria (1988) for socket loosening and the Gie classification (1993) for evaluation of allograft incorporation. Thirty-six (94.7%) sockets were considered radiologically stable (type 0, 1, 2 demarcations) and two (5.3%) sockets were radiologically loose (type 3 demarcations) but there was no socket migration. Twenty-one (55.3%) cases showed good trabecular remodeling (grade 3). Fourteen (36.8 %) cases showed trabecular remodeling (grade 2). Only three (7.9%) cases showed poor allograft incorporation (grade 1). Mean pre-operative hip score was 41 and post-operative hip score was 21. There was one (2.6%) wound infection treated with oral antibiotics and one (2.6%) periprosthetic femoral fracture treated with cables. Furthermore, there was one (2.6%) case of pulmonary embolism and three (7.89%) cases of asymptomatic heterotopic ossification. One year mortality rate was 2.6% (one case) from heart failure but not associated with the surgery. There have been no socket re-revisions (100% survival) at an average of 4 years. At a mean follow up of 4 years, results with the aforementioned technique are comparable to other major studies. Compared to the 40% of minimal loss in obtaining pure cancellous graft less than 10% of initial graft mass is lost without removing the articular cartilage. Particularly when the supply of allograft and operative time are limited retaining the articular cartilage of the femoral head is a safe and effective alternative to be considered

Background. Continuous post-operative infusion of local anaesthetic solutions has been implicated as the causative factor in many cases of chondrolysis. Recent in-vitro studies have shown that even a single exposure to local anaesthetic can cause apoptosis and mitochondrial dysfunction leading to chondrocyte death. Glucosamine has been shown to have a protective and reparative effect on articular cartilage. Aims. To compare the effect of a single exposure of different local anaesthetic solutions on human articular cartilage and to investigate the protective and reparative effects of Glucosamine on articular cartilage exposed to 0.5% Bupivacaine. Methods. Chondral explants (n=354) were obtained from femoral heads of hip fracture patients undergoing hemiarthroplasty. Each specimen was exposed to one of 8 test solutions for one hour. The specimens were then incubated in culture medium containing radio-labelled 35-sulphur for 16 hours. The uptake of 35-S by each specimen was measured to give an estimate of proteoglycan metabolism. Test solutions. 1. 1% Lidocaine 2. 2% Lidocaine 3. 0.25% Bupivacaine, 4. 0.5% Bupivacaine, 5. 0.5% Levo-Bupivacaine 6. Control solution of M199 culture medium. 7. To investigate its protective effect, 100 micrograms of Glucosamine was added along with 0.5% Bupivacaine 8. To investigate its reparative effect, Glucosamine was added after exposure to Bupivacaine for an hour. Results. Compared to the control solution, the inhibition of proteoglycan metabolism was 64% with 1% Lidocaine(p< 0.001), 79% with 2% Lidocaine(p< 0.001), 61% with 0.25% Bupivacaine(p< 0.001), 85% with 0.5% Bupivacaine(p< 0.001) and 77% with 0.5% Levo-Bupivacaine(p< 0.001). Adding Glucosamine reduced Bupivacaine toxicity to 43%(p< 0.001). Glucosamine marginally repaired the damage caused by Bupivacaine, with inhibition of proteoglycan metabolism at 70%(p=0.004). Conclusion. All local anaesthetic solutions were toxic to articular cartilage. The addition of Glucosamine to 0.5% Bupivacaine protected against its toxicity to articular cartilage

Anterior knee pain is one of the most frequently reported musculoskeletal complaints in all age groups. However, patient's complaints are often nonspecific, leading to difficulty in properly diagnosing the condition. One of the causes of pain is the degeneration of the articular cartilage. As the cartilage deteriorates, its ability to distribute the joint reaction forces decreases and the stresses may exceed the pain threshold. Unfortunately, the assessment of the cartilage condition is often limited to a detailed interview with the patient, careful physical examination and x-ray imaging. The X-ray screening may reveal bone degeneration, but does not carry sufficient information of the soft tissues' conditions. More advanced imaging tools such as MRI or CT are available, but these are expensive, time consuming and are only suitable for detection of advanced arthritis. Arthroscopic surgery is often the only reliable option, however due to its semi-invasive nature, it cannot be considered as a practical diagnostic tool. However, as the articular cartilage degenerates, the surfaces become rougher, they produce higher vibrations than smooth surfaces due to higher friction during the interaction. Therefore, it was proposed to detect vibrations non-invasively using accelerometers, and evaluate the signals for their potential diagnostic applications. Vibration data was collected for 75 subjects; 23 healthy and 52 subjects suffering from knee arthritis. The study was approved by the IRB and an Informed Consent was obtained prior to data collection. Five accelerometers were attached to skin around the knee joint (at the patella, medial and lateral femoral condyles, tibial tuberosity and medial tibial plateau). Each subject performed 5 activities; (1) flexion-extension, (2) deep knee bend, (3) chair rising, (4) stair climbing and (5) stair descent. The vibration and motion components of the signals were separated by a high pass filter. Next, 33 parameters of the signals were calculated and evaluated for their discrimination effectiveness (Figure 1). Finally the pattern recognition method based on Baysian classification theorem was used for classify each signal to either healthy or arthritic group, assuming equal prior probabilities. The variance and mean of the vibration signals were significantly higher in the arthritic group (p=2.8e-7 and p=3.7e-14, respectively), which confirms the general hypothesis that the vibration magnitudes increase as the cartilage degenerates. Other signal features providing good discrimination included the 99. th. quantile, the integral of the vibration signal envelope, and the product of the signal envelope and the activity duration. The pattern classification yielded excellent results with the success rate of up to 92.2% using only 2 features, up to 94.8% using 3 (Figure 2), and 96.1% using 4 features. The current study proved that the vibrations can be studied non-invasively using a low-cost technology. The results confirmed the hypothesis that the degeneration of the cartilage increases the vibration of the articulating bones. The classification rate obtained in the study is very encouraging, providing over 96% accuracy. The presented technology has certainly a potential of being used as an additional screening methodology enhancing the assessment of the articular cartilage condition

Aim. This study aims to elucidate the effects of radiofrequency chondroplasty (RFC), a surgical technique for the treatment of damaged articular cartilage, at a microscopic scale. Here we report about two aspects of the study – a morphological analysis of the treated surface using nonlinear microscopy and Raman spectroscopy, and an investigation into changes in permeability to large and small molecules. Cartilage samples were obtained from. Methods. 14 total knee replacement surgeries, which were first treated in vivo with a RFC wand (Arthrocare) using standard arthroscopy technique. Samples for the morphological study were imaged for endogenous fluorescence and collagen, and then imaged using a scanning Raman spectroscope. Samples for the permeability study were incubated in medium containing either Rhodamine or fluorescein labeled albumin, before being sectioned and imaged under a confocal microscope. The morphological study revealed a strong increase in fluorescence in the surface 10 µm, and depletion in collagen signal in the same region, which restores linearly over the adjacent 20–30 µm. Raman spectroscopy showed a spike in β-carrotein in the highly fluorescent surface. Permeability studies show a decrease in permeability to water and an increase in permeability to large molecules, suggesting a remodelling of matrix pores and implications for cell nutrition

Subchondral drillings for articular cartilage defects usually result in fibrocartilage repair, which is inferior biomechanically compared to hyaline cartilage. We postulate that intra-articular injections with autologous marrow-derived stem cells (MSC) and hyaluronic acid (HA) can improve the quality of repair cartilage. We tested this hypothesis in a goat model by creating an articular cartilage defect in the stifle joint and conducted subchondral drillings. The animals were divided into three groups: Group A (control) no injections, Group B (HA) weekly injection of 1 ml sodium hyaluronate for three weeks, Group C (HA+MSC) similar to Group B but with 2 mls autologous MSC in addition to HA. MSC were obtained by bone marrow aspiration, centrifuged, and divided into aliquots, which were cryopreserved. Fifteen animals were equally divided between the groups and sacrificed at 24 weeks after surgery where the joint was harvested and examined macroscopically and histologically. Of the 15 animals, two had died in Group A and one was excluded from Group C due to an infection. In Group A, repair constituted mainly of scar tissue, while in Group B, there was less scar tissue, with small amounts of proteoglycan and collagen II at the osteochondral junction. In contrast, repair cartilage from Group C animals demonstrated almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology as assessed by Gill scoring was significantly better in Group C with one-way ANOVA giving an F-statistic of 10.611 with a p-value of 0.004, which was highly significant. Post-operative intra-articular injections of autologous MSC in combination with HA following subchondral drillings into chondral defects resulted in better cartilage repair

Background. Autologous chondrocyte implantation (ACI) and mosaicplasty (MP) are two methods of repair of symptomatic articular cartilage defects in the adult knee. This study represents the only long-term comparative clinical trial of the two methods. Methods. A prospective, randomised comparison of the two modalities involving 100 patients with symptomatic articular cartilage lesions was undertaken. Patients were followed for ten years. Pain and function were assessed using the modified Cincinnati score, Bentley Stanmore Functional rating system and visual analogue scores. ‘Failure’ was determined by pain, a poor outcome score and arthroscopic evidence of graft disintegration. Results. Patients had a mean age at index operation of 31. There was a long mean pre-op duration of symptoms of seven years and the defects had an average of 1.5 operations (excluding arthroscopy) to the articular cartilage lesion prior to the cartilage repair surgery. The aetiology of the articular cartilage defects was mainly trauma; some patients had osteochondritis dissecans or chondromalacia patellae. Five patients were lost to follow-up. A total of 23 out of 42 mosaicplasty patients failed, 10 out of 58 ACI patients failed (p<0.001). Most patients did well for the first two years when there was a steep failure of mosaicplasty patients, after which the failure rate was more constant. There was a low steady failure rate of ACI over the 10 years. Older patients treated by ACI did worse than younger patients; age was less of a prognostic indicator in MP. Patients irrespective of gender or aetiology of the defect fared better with ACI than MP. Conclusion. At ten years, patients who underwent cartilage repair using ACI fared significantly better than those who underwent mosaicplasty

Introduction. We describe five results of a novel single stage arthroscopic technique for the treatment of articular cartilage defects of the knee. This involves micro drilling and application of Atelo-collagen (Coltrix) and fibrin gel scaffold. Materials and Method. The preclinical study involved two groups of rabbits treated with micro-drilling, and micro-drilling with Atelo-collagen and fibrin gel. New cartilage was subjected to staining with H&E for tissue morphology, toluidine blue (collagen) and safranin O (GAG), immunohistochemistry with antibodies for collagen type I and II, and scanning and transmission electron microscopy to analyse the microstructural morphologies. The micro-drilling with Atelo-collagen, fibrin gel scored better than the micro-drilling alone. Patients (n=30) with symptomatic ICRS grade III/IV chondral defects (lesion size 2–8cm. 2. ) are recruited for this prospective study. The surgical procedure involved micro-drilling and application of Atelo–collagen and fibrin gel under CO. 2. insufflation. Patients underwent morphological evaluation with MRI (T2*-mapping and d-GEMRIC scans). Clinical assessment was done with Lysholm, IKDC and KOOS scores. Radiological assessment was performed with MOCART score. Results. At five years, Lysholm score was 74, compared to 49 pre-operatively (p<0.05). KOOS (symptomatic) improved to 92 from 62 (p<0.05). IKDC (subjective) went to 78 from 40 (p<0.05). The mean T2* relaxation-times for the repair tissue and native cartilage were 26 and 29.9 respectively. Average MOCART score for all lesions was 70. Conclusion. This technique shows encouraging clinical results at five-year follow-up. The morphological MRI shows good cartilage defect filling and the biochemical MRI suggests hyaline like repair tissue

Background:. Full thickness cartilage defect of the knee frequently resulted in fibrous tissue formation, and larger lesions often lead to degenerative arthritis of the knee. Many techniques are designed to repair the cartilage defect including chondrocyte transplantation, microfracture and osteochondral graft. Each method has achieved some success but no universal results. Autologus osteochondral graft has gained in clinical popularity because of its technical feasibility and cost effectiveness. Purpose:. The purpose of this retrospective study was to evaluate the medium-term results of autologous osteochondral graft for focal contained articular cartilage defects of the knee in 25 patients with 26 knees with 2- to 7-year follow-up. Patients and Methods:. The cohort consisted of 17 men and 8 women with an average age of 31.3 ± 11.8 (range 20 to 65) years. One patient had bilateral knees. The diagnosis included 9 osteonecrosis, 10 osteochondritis dessicans, and 7 traumatic defects. A 1.0 mm oversized 10 mm long ossteochondral plug was harvested from either from the sulcus terminalis or the intercondylar notch, and implanted into the recipient site The numbers of osteochondral plug ranged from 1 to 3. In larger lesions, osteochondral grafts were implanted in the weight bearing area, and microfracture in non-weight bearing area. Postoperative management included crutch walking with non-weight bearing for 6 weeks, then partial weight bearing for another 6 weeks before full weight bearing. Range of knee motion, quadriceps and hamstring strengthening exercises were encouraged. The evaluations included functional assessment, radiograph of the knee and second look arthroscopy. Results:. At follow-up of 52.9 ± 20.3 (range 25 to 84) months, the results were 50% excellent, 35% good, 11% fair and 4% poor. Overall satisfactory results were noted in 85%. The improvements in pain and function of the knee ranged from 8 to 16 weeks after surgery. There was no correlation of the clinical results with the diagnosis of the lesion. However, the lesion size greater than 500 mm. 2. is associated with failure. Radiographic degenerative changes were noticed in 6 (23%) and 7 (27%) in medial compartment, 5 (19%) and 5 (19%) in lateral compartment, and 1 (4%) and 2 (8%) in the patellofemoral compartment pre- and postoperatively (P > 0.05). Twelve knees underwent a second look arthroscopy. Of the 11 asymptomatic knees, 8 knees with the defect smaller than 500 mm. 2. showed complete bonding of the graft to the adjacent host cartilage, and 3 cases showed minimal fissuring and fibrous tissue formation between graft and host tissue. One symptomatic knee with greater than 500 mm. 2. lesion showed extensive fibrous tissue between the graft and host cartilage. Conclusion:. Autologous osteochondral graft provides good or excellent results in 85% of patients with focal contained chondral and osteochondral defects of the knee. There was no correlation of the clinical results with the nature of the disease and the size of the lesion smaller than 500 mm. 2. Any lesion larger than 500 mm. 2. is prone to poor clinical outcome

Over the last decade Computer Assisted Orthopaedic Surgery (CAOS) has emerged particularly in the area of minimally invasive Uni-compartmental Knee Replacement (UKR) surgery. Image registration is an important aspect in all computer assisted surgery including Neurosurgery, Cranio-maxillofacial surgery and Orthopaedics. It is possible for example to visualise the patient's medial or lateral condyle on the tibia in the pre-operated CT scan as well as to locate the same points on the actual patient during surgery using intra-operative sensors or probes. However their spatial correspondence remains unknown until image registration is achieved. Image registration process generates this relationship and allows the surgeon to visualise the 3D pre-operative scan data in-relation to the patient's anatomy in the operating theatre. Current image registration for most CAOS applications is achieved through probing along the articulating surface of the femur and tibial plateau and using these digitised points to form a rigid body which is then fitted to the pre-operative scan data using a best fit type minimisation. However, the probe approach is time consuming which often takes 10–15 minutes to complete and therefore costly. Thus the rationale for this study was to develop a new, cost effective, contactless, automated registration method which would entail much lesser time to produce the rigid body model in theatre from the ends of the exposed bones. This can be achieved by taking 3D scans intra-operatively using a Laser Displacement Sensor. A number of techniques using hand held and automated 3D Laser scanners for acquiring geometry of non-reflective objects have been developed and used to scan the surface geometry of a porcine femur with four holes drilled in it. The distances between the holes and the geometry of the bone were measured using digital vernier callipers as well as measurements acquired from the 3D scans. These distances were measured in an open source package MESHLAB version 1.3.2 used for the interpretation, post-processing and analysis of the 3D meshes. Absolute errors ranging from of 0.1 mm to 0.4 mm and the absolute percentage errors ranging from 0.48% to 0.75% were found. Additionally, a pre-calibrated dental model was scanned using a 650 nm FARO™ Laser arm using the global surface registration approach in Geomagic Qualify package and our 3D Laser scanner. Results indicate an average measurement error of 0.16 mm, with deviations ranging from 0.12mm to −0.13 mm and a standard deviation of 0.2 mm. We demonstrated that by acquiring multiple scans of the targets, complete 3D models along with their surface texture can be developed. The overall scanning process, including time required for the post-processing of the data requires less than 20 minutes and is a cost-efficient approach. Moreover, the majority of that time was used in post processing the acquired data which could be potentially reduced through the use of bespoke application software. This project has provided proof of concept for a new automated, non-invasive and cost efficient registration technique with the potential of providing a quantitative assessment of the articular cartilage integrity during lower limb arthroplasty

Chondral defects of the knee are common and often seen in young and active individuals. A novel single stage arthroscopic technique for the treatment of articular cartilage defects in the knee is described. This involves microfracture and application of concentrated bone marrow aspirate cells (BMAC) with fibrin and Hyaluronic Acid as a gel. After a representative preclinical study, the 5 year results of a prospective clinical study are presented. The pre-clinical study involved two groups of rabbits with standardised lesions treated with microfracture alone and microfracture combined with fibrin/HA/BMAC application. New cartilage from both groups was subjected to staining with H&E for tissue morphology, toluidine blue (collagen) and safranin O (GAG), immunohistochemistry with antibodies for collagen type I and II, and scanning and transmission electron microscopy to analyse the microstructural morphologies. The fibrin/HA/BMAC group scored better than the microfracture group on all tests. A subsequent prospective clinical study patients (n=60) with symptomatic ICRS grade III/IV chondral defects (lesion size 2–8cm2). The surgical procedure involved debridement of the lesion, micro-fracture and application of fibrin/HA/BMAC gel under CO2 insufflation. Patients underwent morphological evaluation with MRI (T2*-mapping and d-GEMRIC scans). Clinical assessment employed the Lysholm, IKDC and KOOS scores while radiological assessment was performed with MOCART score. At 5 years, Lysholm score was 78, compared to 51 pre-operatively (p<0.05). KOOS (symptomatic) improved to 90 from 66 (p<0.05). IKDC (subjective) went to 80 from 39 (p<0.05). The mean T2* relaxation-times for the repair tissue and native cartilage were 26 and 29.9 respectively. Average MOCART score for all lesions was 70. This technique shows encouraging clinical results at 5 year follow-up. The morphological MRI shows good cartilage defect filling and the biochemical MRI suggests hyaline like repair tissue

Subchondral drillings for articular cartilage repair give functional improvement that peaks at 24 months after surgery. We postulate that intra-articular injections with autologous peripheral blood stem cells (PBSC) and hyaluronic acid (HA) following subchondral drillings can improve the repair process. Thirty-four patients with full thickness chondral defects of the knee joint underwent subchondral drillings. The operated knees were then placed on continuous passive motion for a period of two hours per day for four weeks, with partial weight-bearing for the first six weeks. PBSC were harvested by apheresis and divided into aliquots which were cryopreserved. One week after surgery, weekly intra-articular injections of 2.5 mLs PBSC mixed with 2 mLs of sodium hyaluronate were given for five weeks after surgery. Patients were followed up for an average of 11 months (range 6–20) and assessed using serial MRI scans. Second look arthroscopy and chondral biopsies were obtained in five patients. International Knee Documentation Committee (IKDC) scores were compared with previous microfractures results from the Mithoefer cohort study using linear interpolation to generate time-based predicted values. The difference was compared using a two-tailed, one-sample T-test against a value of zero. Serial MRI scans showed healing of subchondral bone and evidence of cartilage regeneration that was confirmed on arthroscopy with good integration into surrounding cartilage with no delamination. Biopsy specimens showed attributes typical of hyaline cartilage with good cellular morphology, abundant proteoglycans and Type II collagen. No oedema or degenerative changes were seen. The IKDC data was on average 12.8 points (95% CI 6.5-19.1) higher than the Mithoefer group with p=0.0002. Intra-articular injections of PBSC and HA following subchondral drillings resulted in good repair tissue based on MRI, arthroscopic, and histological criteria, with IKDC scores superior to standard microfracture surgery

Introduction

Hemiarthroplasty is an attractive technique for young and active patients as it preserves more bone stock. Polycarbonate urethane (PCU) has recently been introduced as an alternative bearing material. DSM Biomedical BV (Geleen, The Netherlands) has modified Bionate^® PCU 80A (80AI) with C18 groups and produce Bionate^® II PCU 80A (80AII) to create a different biointerface and enhance its tribological properties. The aim of this study was to compare friction performance of the articulation of the cartilage against 80AI and 80AII in various lubricants.

Difficulties arise when counselling younger patients on the long-term sequelae of a minor knee chondral defect. This study assesses the natural history of patients with grade 2 Outerbridge chondral injuries of the medial femoral condyle at arthroscopy. We reviewed all arthroscopies performed by one surgeon over 12 years with Outerbridge grade 2 chondral defects. Patients aged 30 to 59 were included. Meniscal injuries found were treated with partial menisectomy. All patients had five-year follow up minimum. Primary outcome measure was further interventions of total or unicondylar arthroplasty or high tibial osteotomy. We analysed 3,344 arthroscopies. Average follow up was 10 years (Range 5–17 years). A total of 357 patients met inclusion criteria of which 86 had isolated medial femoral condyle disease. Average age was 50 at the time of arthroscopy. Average BMI at surgery was 31.7 and average chondral defect area was 450 mm². Isolated MFC chondral disease had a 10.5% intervention rate. Intervention occurred at a mean of 8.5 years post primary arthroscopy. In young patients Outerbridge II chondral injuries affecting ≥2 compartments have a high rate of further intervention within a decade. This information is crucial in counselling young patients on long-term sequelae of benign chondral lesions.

Purpose

The prevalence of focal chondral lesions reported inthe literature during knee arhroscopy can be as high as 63%. Of these, more than half are either grade III or grade IV lesions (Outerbridge). Full thickness cartilage lesions ranging from 2cm2 to 10cm2 are the most challenging to treat. To goal of this study was to evaluate clinical outcomes of pain, function and quality of life, along with radiological outcomes of cartilage repair using microfracture, autologous minced cartilage and polymeric scaffold.

Osteoarthritis (OA) is a disease of the synovial joint with synovial inflammation, capsular contracture, articular cartilage degradation, subchondral sclerosis and osteophyte formation contributing to pain and disability. Transcriptomic datasets have identified genetic loci in hip and knee OA demonstrating joint specificity. A limited number of studies have directly investigated transcriptional changes in shoulder OA. Further, gene expression patterns of periarticular tissues in OA have not been thoroughly investigated. This prospective case control series details transcriptomic expression of shoulder OA by analysing periarticular tissues in patients undergoing shoulder replacement for OA as correlated with a validated patient reported outcome measure of shoulder function, an increasing (clinically worsening) QuickDASH score. We then compared transcriptomic expression profiles in capsular tissue biopsies from the OA group (N=6) as compared to patients undergoing shoulder stabilisation for recurrent instability (the control group, N=26). Results indicated that top ranked genes associated with increasing QuickDASH score across all tissues involved inflammation and response to stress, namely interleukins, chemokines, complement components, nuclear response factors and immediate early response genes. Some of these genes were upregulated, and some downregulated, suggestive of a state of flux between inflammatory and anti-inflammatory signalling pathways. We have also described gene expression pathways in shoulder OA not previously identified in hip and knee OA, as well as novel genes involved in shoulder OA