Objectives. The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model. Methods. MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically. Results. The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF. Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups. Conclusions. G-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model. Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123–131. DOI: 10.1302/2046-3758.63.BJR-2016-0083

Objectives. Previously, we reported the improved transfection efficiency of a plasmid DNA-chitosan (pDNA-CS) complex using a phosphorylatable nuclear localization signal-linked nucleic kinase substrate short peptide (pNNS) conjugated to chitosan (pNNS-CS). This study investigated the effects of pNNS-CS-mediated miR-140 and interleukin-1 receptor antagonist protein (IL-1Ra) gene transfection both in rabbit chondrocytes and a cartilage defect model. Methods. The pBudCE4.1-miR-140, pBudCE4.1-IL-1Ra, and negative control pBudCE4.1 plasmids were constructed and combined with pNNS-CS to form pDNA/pNNS-CS complexes. These complexes were transfected into chondrocytes or injected into the knee joint cavity. Results. High IL-1Ra and miR-140 expression levels were detected both in vitro and in vivo. In vitro, compared with the pBudCE4.1 group, the transgenic group presented with significantly increased chondrocyte proliferation and glycosaminoglycan (GAG) synthesis, as well as increased collagen type II alpha 1 chain (COL2A1), aggrecan (ACAN), and TIMP metallopeptidase inhibitor 1 (TIMP-1) levels. Nitric oxide (NO) synthesis was reduced, as were a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS-5) and matrix metalloproteinase (MMP)-13 levels. In vivo, the exogenous genes reduced the synovial fluid GAG and NO concentrations and the ADAMTS-5 and MMP-13 levels in cartilage. In contrast, COL2A1, ACAN, and TIMP-1 levels were increased, and the cartilage Mankin score was decreased in the transgenic group compared with the pBudCE4.1 group. Double gene combination produced greater efficacies than each single gene, both in vitro and in vivo. Conclusion. This study suggests that pNNS-CS is a good candidate for treating cartilage defects via gene therapy, and that IL-1Ra in combination with miR-140 produces promising biological effects on cartilage defects. Cite this article: R. Zhao, S. Wang, L. Jia, Q. Li, J. Qiao, X. Peng. Interleukin-1 receptor antagonist protein (IL-1Ra) and miR-140 overexpression via pNNS-conjugated chitosan-mediated gene transfer enhances the repair of full-thickness cartilage defects in a rabbit model. Bone Joint Res 2019;8:165–178. DOI: 10.1302/2046-3758.83.BJR-2018-0222.R1

Objectives. The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage. Methods. Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored. Results. The CBA group showed similar results to the autologous group in biomechanical properties, Moran’s criteria, histological tests and Wakitani histological scoring. Conclusions. These results suggest that tissue-engineered cartilage constructed using the CBA technique could be used effectively to repair cartilage defects in the weight-bearing area of joints. Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R. Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin binding technique for the repairing of cartilage defects in the weight-bearing area of knee joints in pigs. Bone Joint Res 2017;6:–295. DOI: 10.1302/2046-3758.65.BJR-2016-0277

Microfracture is frequently used as the first line of treatment for the repair of traumatic cartilage defects. We present the clinical and histological results 18 months to two-years after treatment in a 26-year-old male with a post-traumatic chondral defect of the medial femoral condyle managed by microfracture covered with chondrotissue, a cell-free cartilage implant made of a resorbable polyglycolic acid felt and hyaluronic acid

Introduction: Within the last few years numerous operative procedures have been described aiming a biological repair of damaged articular cartilage. Current techniques are: Microfracture, Osteochondral Autografting (Mosaicplasty) and Autologous Chondrocyte Transplantation (ACT). Several new studies have shown, that the defect size plays a major role in the clinical outcome of the different procedures. Thus, it makes sense to measure the size of a cartilage defect before indicating a certain method for biological repair. Material and Methods: We have developed a software (beta-version) for measuring the size of a cartilage defect during a routine arthroscopy in a real-time mode. The programme is based on an Infrared-Navigation tool (Orthopilot, B.Braun-Aesculap, Germany). In order to proof the reliability and the usefulness of this device, we carried out following study: in each of 6 cadaver-knees we performed 2 full-thickness cartilage defects (MFC and LFC) of different size. In a first run 3 surgeons had to scope the joint and estimate the defect size with means of a scaled probe-hook. In a second run we performed a measurement of the defect with the Orthopilot™; finally an open measurement after arthrotomy was done to act as reference. Results: Measurement of the cartilage defect size was clearly superior to an estimation by probehook. Especially the inter-observer difference between the surgeons was widely spread, whereas the max. mismeasurement with the Orthopilot was 2mm. Discussion: Our study has shown, that navigational-assisted determination of chondral defects is superior to a simple estimation of a defect size by a probehook. Considering that the defect size is a crucial point in choosing the appropriate procedure for the treatment of cartilage defects, navigation devices like the CDM-software is maybe a helpful tool in making the right decision for a suitable method of biological cartilage repair

We describe the outcome at a mean follow-up of 8.75 years (7.6 to 9.8) of seven patients who had undergone osteochondral autologous transplantation for full-thickness cartilage defects of the shoulder between 1998 and 2000. These patients have been described previously at a mean of 32.6 months when eight were included. One patient has been lost to follow-up. The outcome was assessed by the Constant shoulder score and the Lysholm knee score to assess any donor-site morbidity. Standard radiographs and MR scores were obtained and compared with the pre-operative findings and the results from the previous review. No patient required any further surgery on the shoulder. The mean Constant score improved significantly until the final follow-up (p = 0.018). The Lysholm score remained excellent throughout. There was a significant progression of osteoarthritic changes from the initial surgery to the first and final follow-up but this did not appear to be related to the size of the defect, the number of cylinders required or the Constant score (p = 0.016). MRI showed that all except one patient had a congruent joint surface at the defect with full bony integration of all osteochondral cylinders. The results have remained satisfactory over a longer period with very good objective and subjective findings

Aims

The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model.

In 16 mature New Zealand white rabbits mesenchymal stem cells were aspirated from the bone marrow, cultured in monolayer and implanted on to a full-thickness osteochondral defect artificially made on the patellar groove of the same rabbit. A further 13 rabbits served as a control group. The rabbits were killed after 14 weeks. Healing of the defect was investigated histologically using haematoxylin and eosin and Safranin-O staining and with immunohistochemical staining for type-II collagen. We also used a reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA of type-I and type-II collagen. The semiquantitative histological scores were significantly higher in the experimental group than in the control group (p < 0.05). In the experimental group immunohistochemical staining on newly formed cartilage was more intense for type-II collagen in the matrix and RT-PCR from regenerated cartilage detected mRNA for type-II collagen in mature chondrocytes. These findings suggest that repair of cartilage defects can be enhanced by the implantation of cultured mesenchymal stem cells

In an experimental study in rabbits, bone and cartilage regeneration could be achieved with a new class of resorbable bio-implants. These implants consist of an open porous structure made from polylacitdes and an open porous fleece made from polyglactin/polydioxanon. Both layers were not separated from each other, thus allowing mesenchymal cells to penetrate freely from bone into both the bone substitute and the cartilage substitute layer. It could be shown that ostochondral defects of 4mm diameter and 6mm depth in the condyle of the knee of rabbits healed by the process of mesenchymal cell differentiation into osteocytes and chondrocytes triggered by mechanical load induction only. Evaluation of the newly formed cartilage by light microscopy and immunohistology showed hyaline like features. However, in many clinical cases chondral defects occur without substantial accompanying bone loss. In these situations, reconstruction of the cartilage defects only seems to be sufficient. However, fixation of such fleeces onto the bone is difficult. On one hand, adherence of the fleece to the underlying bone is crucial, on the other hand an open connection from the bone to the fleece must be accomplished in order to allow mesenchymal cells to penetrate the fleece. Therefor, any kind of glue fixation is not appropriate. To overcome this problem, a new fixation method was developed which allows a safe connection of the fleece onto the bone while providing an open contact of the fleece to the bone marrow for unhampered migration of mesenchymal cells. The new “Cartilage patches” consist of a fleece (serving as the cartilage substitute layer) made from polyglactin/polydioxanon which had proven its applicability in the above mentioned experiments. Fixation of fleece was achieved by “darts” which were glued onto the fleece. The darts were made from polylacitdes, thus providing sufficient mechanical stability in the bone. During operation, small holes are cut into the bone by a special instrument. The holes are located in such a way that the darts of the cartilage patch fit into them, such resulting in a stable fixation of the fleece onto the underlying bone. Blood containing mesenchymal cells from the bone marrow is able to flow from the holes into the fleece. In a biomechanical analysis the adherence of the cartilage patches were tested with respect to shear resistance and pull-out stabillity. The results of the tests show that the new cartilage patches withstand the mechanical stress exerted onto articular surfaces and can serve as a new class of cartilage substitute layers. In an animal experiment the applicability of the cartilage patches in reconstruction of cartilage defects in the knee joint of sheep will be proven

We reviewed retrospectively 11 patients who had been treated surgically by open autologous osteochondral grafting for symptomatic chondral or osteochondral defects of the dome of the talus between 1996 and 1999. The mean ages of the eight men and three women were 34.2 and 25.9 years, respectively, with a mean time to follow-up of 24 months. The results of functional outcome were prospectively obtained using the MODEMS AAOS foot and ankle follow-up questionnaire, the AOFAS ankle-hindfoot scale and the Hannover scores for the ankle.

The grafts were harvested from the ipsilateral knee. Good to excellent results were obtained for the ankle without adverse effects on the knee. We believe that autologous osteochondral grafting should be considered for the patient with a symptomatic osteochondral defect of the talus.

We investigated the clinical, arthroscopic and biomechanical outcome of transplanting autologous chondrocytes, cultured in atelocollagen gel, for the treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a minimum period of 25 months. Transplantation eliminated locking of the knee and reduced pain and swelling in all patients. The mean Lysholm score improved significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good or excellent outcome. There were few adverse features, except for marked hypertrophy of the graft in three knees, partial detachment of the periosteum in three and partial ossification of the graft in one. Biomechanical tests revealed that the transplants had acquired a hardness similar to that of the surrounding cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases

Abstract. Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or AMIC-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for PFJ instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or Autologous Matrix-Induced Chondrogenesis(AMIC)-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for patellofemoral instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre

Abstract. Objectives. Little is known about the impact of cartilage defects on knee joint biomechanics. This investigation aimed to determine the gait characteristics of patients with symptomatic articular cartilage lesions of the knee. Methods. Gait analyses were performed at the Regional North-West Joint Preservation Centre. Anthropometric measurements were obtained, then 16 retroreflective markers representing the Plug-in-Gait biomechanical model were placed on pre-defined anatomical landmarks. Participants walked for two minutes at a self-selected speed on a treadmill on a level surface, then for 2 minutes downhill. A 15-camera motion-capture system recorded the data. Knee kinematics were exported into Matlab to calculate the average kinematics and spatiotemporal parameters per patient across 20 gait cycles. Depending on the normality of the data, paired t-tests or Wilcoxon ranked tests were performed to compare both knees (α = 0.05). Results. 20 patients participated; one of whom has bilateral cartilage defects. All 20 data sets were analysed for level walking; 18 were analysed for downhill walking. On a level surface, patients walked at an average speed of 3.1±0.8km/h with a cadence of 65.5±15.3 steps/minute. Patients also exhibited equal step lengths (0.470±0.072m vs 0.471±0.070m: p=0.806). Downhill, the average walking speed was 2.85±0.5km/h with a cadence of 78.8±23.1 steps/minute and step lengths were comparable (0.416±0.09m vs 0.420±0.079m: p=0.498). During level walking, maximum flexion achieved during swing did not differ between knees (54.3±8.6° vs 55.5±11.0°:p=0.549). Neither did maximal extension achieved at heel strike (3.1±5.7° vs 5.4±4.7°:p=0.135). On average, both knees remained in adduction throughout the gait cycle, with the degree of adduction greater in flexion in the operative knee. However, differences in maximal adduction were not significant (22.4±12.4° vs 18.7±11.0°:p=0.307). Maximal internal-external rotation patterns were comparable in stance (0.9±7.7° vs 3.5±9.8°: p=0.322) and swing (7.7±10.9° vs 9.8±8.3°:p=0.384). During downhill walking, maximum flexion also did not differ between operative and contralateral knees (55.38±10.6° vs 55.12±11.5°:p=0.862), nor did maximum extension at heel strike (1.32±6.5° vs 2.73±4.5°:p=0.292). No significant difference was found between maximum adduction of both knees (15.87±11.0° vs 16.78±12.0°:p=0.767). In stance, differences in maximum internal-external rotation between knees were not significant (5.39±10.7° vs 6.10±11.8°:p=0.836), nor were they significant in swing (7.69±13.3° vs 7.54±8.81°:p=0.963). Conclusions. Knee kinematics during level and downhill walking were symmetrical in patients with a cartilage defect of the knee, but an increased adduction during flexion in the operative knee may lead to pathological loading across the medial compartment of the knee during high flexion activities. Future work will investigate this further and compare the data to a healthy young population. We will also objectively assess the functional outcome of this joint preservation surgery to monitor its success. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Cartilage defects of the hip cause significant pain and may lead to arthritic changes that necessitate hip replacement. We propose the use of fresh osteochondral allografts as an option for the treatment of such defects in young patients. Here we present the results of fresh osteochondral allografts for cartilage defects in 17 patients in a prospective study. The underlying diagnoses for the cartilage defects were osteochondritis dissecans in eight and avascular necrosis in six. Two had Legg-Calve-Perthes and one a femoral head fracture. Pre-operatively, an MRI was used to determine the size of the cartilage defect and the femoral head diameter. All patients underwent surgical hip dislocation with a trochanteric slide osteotomy for placement of the allograft. The mean age at surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months (3 to 74). The mean Harris hip score was significantly better after surgery (p < 0.01) and 13 patients had fair to good outcomes. One patient required a repeat allograft, one patient underwent hip replacement and two patients are awaiting hip replacement. Fresh osteochondral allograft is a reasonable treatment option for hip cartilage defects in young patients. Cite this article: Bone Joint J 2014;96-B(11 Supple A):11–16

Osteoarthritis (OA) affects bone cartilage and underlying bone. Mechanically, the underlying bone provides support to the healthy growth of the overlying cartilage. However, with the progress of OA, bone losses and cysts occur in the bone and these would alter the biomechanical behaviour of the joint, and further leading to bone remodelling adversely affect the overlying cartilage. Human femoral head and femoral condyle were collected during hip or knee replacement operation due to the end stage of osteoarthritis (age 50–70), and the cartilage patches were graded and marked. A volunteer patient, with minor cartilage injury in his left knee while the right knee is intact, was used as control. Peripheral quantitative computed tomography (pQCT) was used to scan the bone and to determine the volumetric bone mineral density (vBMD) distribution. The examination of retrieved tissue explants from osteoarthritic patients revealed that patches of cartilage were worn away from the articular surface, and patches of intact cartilage were left. The cysts, ranging from 1 to 10mm were existed in all osteoarthritic bones, and were located close to cartilage defects in the weight-bearing regions, and closely associated with the grade of cartilage defect as measured by pQCT. The bone mineral density (vBMD) distribution demonstrated that the bones around cysts had much higher vBMD than the trabecular bone away from the cysts. Compared to the subchondral bone under thicker cartilage, subchondral bone within cartilage defect has higher vBMD. This may result from the mechanical stimulation as a result of bone-bone direct contact with less protection of cartilage in cartilage defect regions. This study showed an association between cartilage defect and subchondral bone mineral density distribution. Cysts were observed in all osteoarthritic samples and they are located close to cartilage defects in the weight-bearing regions. Cartilage defect altered the loading pattern of the joints, this leading to the bone remodelling and resultant bone structural changes as compared to the normal bone tissues. This work was financially supported by The ARUK Proof of Concept Award (grant no: 21160)

Osteoarthritis (OA), the most prevalent chronic joint disease, represents a relevant social and economic burden worldwide. Human umbilical cord mesenchymal stem cells (HUCMSCs) have been used for injection into the joint cavity to treat OA. The aim of this article is to clarify whether Huc-MSCs derived exosomes could inhibit the progression of OA and the mechanism in this process. A rabbit OA model was established by the transection of the anterior cruciate ligament. The effects of HUCMSCs or exosomes derived from HUCMSCs on repairing articular cartilage of knee osteoarthritis was examined by micro-CT. Immunohistochemical experiments were used to confirm the expression of relevant inflammatory molecules in OA. In vitro experiments, Transwell assay was used to assess the migration of macrophages induced by TNF-a. Results showed that a large number of macrophages migrated in arthcular cavity in OA model in vivo, while local injection of HUCMSCs and exosomes did repair the articular cartilage. Immunohistochemical results suggested that the expression of CCL2 and CD68 in the OA rabbit model increased significantly, but was significantly reduced by HUCMSCs or exosomes. Transwell assay showed that both HUCMSCs and exosomes can effectively inhibit the migration of macrophage. In conclusion, the exosomes derived by HUCMSCs might might rescue cartilage defects in rabbit through its anti-inflammatory effects through inhibiting CCL2

Femoroacetabular impingement is a prearthritic deformity frequently associated with early chondral damage. Several techniques exist for restoring larger cartilage defects. While AMIC proved to be an effective treatment in knee and ankle, there are only short-term data available in hip. This study aimed to investigate the mid-term clinical outcome of patients with chondral lesions treated by AMIC and evaluate the quality of repair tissue via MRI. This retrospective, single center study includes 18 patients undergoing surgical hip dislocation for FAI between 2013 and 2016. Inclusion criteria were: cam or pincer-type FAI, femoral or acetabular chondral lesions > 1 cm. 2. , (IRCS III-IV). Due to exclusion criteria and loss-to-follow-up 9 patients (10 hips) could be included. Patient reported outcome measures included Oxford Hip Score (OHS) & Core Outcome Measure Index (COMI)). MRIs were evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. None of the patients underwent revision surgery except screw removals from the greater trochanter. Followup data indicate a satisfactory to good hip function at 5 years: PROMS improved from pre- to postop at 5 years: OHS from 38.1 to 43.4, COMI from to 1.8 and UCLA from 4 to 8.1 respectively. MOCART score was 67.5 postoperatively. Subgrouping showed slightly better results for acetabular defects (Ø 69.4) compared femoral defects (Ø 60). Based on the reported mid-term results, we consider AMIC as a valuable treatment option for larger chondral defects of the hip

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

Abstract. Background. Osteochondral allograft (OCA) transplantation is a clinically and cost-effective option for symptomatic cartilage defects. In 2017 we initiated a program for OCA transplantation for complex chondral and osteochondral defects as a UK tertiary referral centre. Aim. To characterise the complications, re-operation rate, graft survivorship and clinical outcomes of knee OCA transplantation. Methodology. Analysis of a prospectively maintained database of patients treated with primary OCA transplantation from 2017 to 2021 with a minimum of one-year follow-up. Patient reported outcome measures (PROMs), complications, re-operations and failures were evaluated. Results. 37 patients with 37 knee OCA procedures were included (mean age 31.6 years [16–49 years]). Mean BMI 26.6 kg/m2 (19.1–35.9 kg/m2). The mean chondral defect size was 3cm2 (1.2–7.3 cm2). Mean duration of follow-up was 3.1 years (1–5.3 years). 16 patients underwent meniscal allograft transplantation (MAT), 6 underwent osteotomy and 4 underwent ligament reconstruction as concurrent procedures. Significant improvements in mean PROMs were noted at 12 months. 16 patients had reoperations of which 5 had more than one surgery. Of these patients 6 were related to OCA (mainly debridement and revision OCA in one patient), and the remainder were related to additional procedures including removal of plate in 2 patients. The overall failure rate was 1 in 37 patients (3%). Conclusions. Early experience of OCA as a treatment option for complex chondral and osteochondral lesions in the knee shows satisfactory results. The reoperation rate is high but at mean follow-up of 3.1 years the survival rate was 97%

The regenerative capacity of hyaline cartilage is greatly limited. To prevent the onset of osteoarthritis, cartilage defects have to be properly treated. Cartilage, tissue engineered by mean of bioactive glass (BG) scaffolds presents a promising approach. Until now, conventional BGs have been used mostly for bone regeneration, as they are able to form a hydroxyapatite (HA) layer and are therefore, less suited for cartilage reconstruction. The aim of this study is to compare two BGs based on a novel BG composition tailored specifically for cartilage (CAR12N) and patented by us with conventional BG (BG1393) with a similar topology. The highly porous scaffolds consisting of 100% BG (CAR12N, CAR12N with low Ca2+/Mg2+ and BG1393) were characterized and dynamically seeded with primary porcine articular chondrocytes (pACs) or primary human mesenchymal stem cells (hMSCs) for up to 21 days. Subsequently, cell viability, DNA and glycosaminoglycan contents, cartilage-specific gene and protein expression were evaluated. The manufacturing process led to a comparable high (over 80%) porosity in all scaffold variants. Ion release and pH profiles confirmed bioactivity for them. After both, 7 and 21 days, more than 60% of the total surfaces of all three glass scaffold variants was densely colonized by cells with a vitality rate of more than 80%. The GAG content was significantly higher in BG1393 colonized with pACs. In general, the GAG content was higher in pAC colonized scaffolds in comparison to those seeded with hMSCs. The gene expression of cartilage-specific collagen type II, aggrecan, SOX9 and FOXO1 could be detected in all scaffold variants, irrespectively whether seeded with pACs or hMSCs. Cartilage-specific ECM components could also be detected at the protein level. In conclusion, all three BGs allow the maintenance of the chondrogenic phenotype or chondrogenic differentiation of hMSCs and thus, they present a high potential for cartilage regeneration

Autologous osteochondral grafting has demonstrated positive outcomes for treating articular cartilage defects by replacing the damaged region with a cylindrical graft consisting of bone with a layer of cartilage, taken from a non-loadbearing region of the knee. Despite positive clinical use, factors that cause graft subsidence or poor integration are relatively unknown. The aim of this study was to develop finite element (FE) models of osteochondral grafts within a tibiofemoral joint and to investigate parameters affecting osteochondral graft stability. Initial experimental tests on cadaveric femurs were performed to calibrate the bone properties and graft-bone frictional forces for use in corresponding FE models, generated from µCT scan data. The effects of cartilage defects and osteochondral graft repair were measured by examining contact pressure changes using in vitro tests on a single cadaveric human tibiofemoral joint. Six defects were created in the femoral condyles which were subsequently treated with osteochondral autografts or metal pins. Matching µCT scan-based FE models were created, and the contact patches were compared. Sensitivity to graft bone properties was investigated. The bone material properties and graft-bone frictional forces were successfully calibrated from the initial tests with good resulting levels of agreement (CCC=0.87). The tibiofemoral joint experiment provided a range of cases to model. These cases were well captured experimentally and represented accurately in the FE models. Graft properties relative to host bone had large effects on immediate graft stability despite limited changes to resultant cartilage contact pressure. Model confidence was built through extensive validation and sensitivity testing, and demonstrated that specimen-specific properties were required to accurately represent graft behaviour. The results indicate that graft bone properties affect the immediate stability, which is important for the selection of allografts and design of future synthetic grafts. Acknowledgements. Supported by the EPSRC-EP/P001076

Abstract. Introduction. The incidence of significant acute chondral injuries with patella dislocation is around 10–15%. It is accepted that chondral procedures should only be performed in the presence of joint stability. Methodology. Patients were identified from surgeon/hospital logs. Patient demographics, lesion size and location, surgical procedure, patient reported outcome measures, post-operative MR imaging and complications were recorded. PROMs and patient satisfaction was obtained. Results. 20 knees (18 patients) were included. Mean age was 18.6 years (range; 11–39) and the mean follow-up was 16.6 months (range; 2–70). The defect locations were the lateral femoral condyle (9/20; 45%), patella (9/20; 45%), medial femoral condyle (1/20; 5%) and the trochlea (1/20; 5%). The mean defect size was 2.6cm2. Twelve knees were treated with cartilage fixation, 5 with microfracture and 3 with OATS. At follow up, the overall mean Lysholm score was 77.4 (± 17.1) with no chondral regenerative procedure being statistically superior. There was no difference in Lysholm scores between those patients having acute medial patellofemoral ligament reconstruction versus medial soft tissue plication (p=0.59). Five (25%) knees required re-operation (one arthroscopic arthrolysis; one patella chondroplasty; two removal of loose bodies; one implant adjustment). Overall 90% responded as being satisfied with surgery. Conclusion. Our aggressive pathway to identify and treat acute cartilage defects with early operative intervention and patella stabilisation has shown high rates of satisfaction and Lysholm scores with no major revisions. The full range of chondral restoration options should be considered by surgeons managing these patients

Damage to articular cartilage is difficult to treat, as it has a low capacity to regenerate. Biomimetic natural polymer scaffolds can potentially be used to regenerate cartilage. Collagen hyaluronic acid (CHyA) scaffolds have been developed in our laboratory to promote cell infiltration and repair of articular cartilage. However, the low mechanical properties of such scaffolds potentially limit their use to the treatment of small cartilage defects. 3D-printed polymers can provide a reinforcing framework in these scaffolds, thus allowing their application in the treatment of larger defects. The aim of this study was to create mechanically functional biomaterial scaffolds by incorporating a CHyA matrix into 3D-printed polymer meshes resulting in an integrated porous material composite with improved mechanical properties for repair of large cartilage defects. 3D-printed meshes were developed to facilitate an architecture suitable for nutrient flow, cell infiltration, and even CHyA incorporation. And the meshes were freeze dried in custom made moulds to create a pore structure suitable for chondrogenesis. Uniaxial compressive testing of the scaffolds revealed improved mechanical properties following reinforcement with printed meshes, with the compressive modulus increasing from 0.8kPa (alone) to 0.5MPa (reinforced structure). The reinforced scaffolds maintained interconnected pores with the mean pore diameter increasing from 130 to 175µm. The reinforcement had no negative impact on MSC viability, with 90.1% viability in reinforced scaffolds at day 7. The compressive modulus of the reinforced CHyA scaffold is close to native articular cartilage, suggesting that this approach can be used for treatment of large cartilage defects

Mincing cartilage with commercially available shavers is increasingly used for treating focal cartilage defects. This study aimed to compare the impact of mincing bovine articular cartilage using different shaver blades on chondrocyte viability. Bovine articular cartilage was harvested using a scalpel or three different shaver blades (2.5 mm, 3.5 mm, or 4.2 mm) from a commercially available shaver. The cartilage obtained with a scalpel was minced into fragments smaller than 1 mm. 3. All four conditions were cultivated in a culture medium for seven days. After Day 1 and Day 7, metabolic activity, RNA isolation, and gene expression of anabolic (COL2A1, ACAN) and catabolic genes (MMP1, MMP13), Live/Dead staining and visualization using confocal microscopy, and flow cytometric characterization of minced cartilage chondrocytes were measured. The study found that mincing cartilage with shavers significantly reduced metabolic activity after one and seven days compared to scalpel mincing (p<0.001). Gene expression of anabolic genes was reduced, while catabolic genes were increased after day 7 in all shaver conditions. The MMP13/COL2A1 ratio was also increased in all shaver conditions. Confocal microscopy revealed a thin line of dead cells at the lesion site with viable cells below for the scalpel mincing and a higher number of dead cells diffusely distributed in the shaver conditions. After seven days, there was a significant decrease in viable cells in the shaver conditions compared to scalpel mincing (p<0.05). Flow cytometric characterization revealed fewer intact cells and proportionally more dead cells in all shaver conditions compared to the scalpel mincing. Mincing bovine articular cartilage with commercially available shavers reduces the viability of chondrocytes compared to scalpel mincing. This indicates that mincing cartilage with a shaver should be considered a matrix rather than a cell therapy. Further experimental and clinical studies are required to standardize the mincing process with a shaver. Acknowledgements: This study received unrestricted funding from KARL STORZ SE & Co. KG

We studied whether the presence of lateral osteophytes on plain radiographs was a predictor for the quality of cartilage in the lateral compartment of patients with varus osteoarthritic of the knee (Kellgren and Lawrence grade 2 to 3). The baseline MRIs of 344 patients from the Osteoarthritis Initiative (OAI) who had varus osteoarthritis (OA) of the knee on hip-knee-ankle radiographs were reviewed. Patients were categorised using the Osteoarthritis Research Society International (OARSI) osteophyte grading system into 174 patients with grade 0 (no osteophytes), 128 grade 1 (mild osteophytes), 28 grade 2 (moderate osteophytes) and 14 grade 3 (severe osteophytes) in the lateral compartment (tibia). All patients had Kellgren and Lawrence grade 2 or 3 arthritis of the medial compartment. The thickness and volume of the lateral cartilage and the percentage of full-thickness cartilage defects in the lateral compartment was analysed. There was no difference in the cartilage thickness or cartilage volume between knees with osteophyte grades 0 to 3. The percentage of full-thickness cartilage defects on the tibial side increased from < 2% for grade 0 and 1 to 10% for grade 3. The lateral compartment cartilage volume and thickness is not influenced by the presence of lateral compartment osteophytes in patients with varus OA of the knee. Large lateral compartment osteophytes (grade 3) increase the likelihood of full-thickness cartilage defects in the lateral compartment. Cite this article: Bone Joint J 2015;97-B:1634–9

Long-term regeneration of cartilage defects treated with tissue engineering constructs often fails because of insufficient integration with the host tissue. We hypothesize that construct integration will be improved when implants actively interact with and integrate into the subchondral bone. Growth and Differentiation Factor 5 (GDF-5) is known to support maturation of chondrocytes and to enhance chondrogenic differentiation and hypertrophy of mesenchymal stromal cells (MSC). Therefore, we investigated whether GDF-5 is capable to stimulate endochondral ossification of MSC in vitro and in vivo and would, thus, be a promising candidate for augmenting fibrin glue in order to support integration of tissue engineering constructs into the subchondral bone plate. To evaluate the adhesive strength of fibrin glue versus BioGlue. ®. , a commercially available glue used in vascular surgery, an ex vivo cadaver study was performed and adhesion strength was measured via pull-out testing. MSC were suspended in fibrin glue and cultivated in chondrogenic medium with and without 150 ng/mL GDF-5. After 4 weeks, the formed cartilage was evaluated and half of the constructs were implanted subcutaneously into immunodeficient mice. Endochondral ossification was evaluated after 2 and 4 weeks histologically and by microCT analysis. BioGlue. ®. and GDF-5-augmented fibrin glue were tested for 4 weeks in a minipig cartilage defect model to assess their orthotopic biocompatibility. Pull-out testing revealed sufficient adhesive strength of fibrin glue to fix polymeric CellCoTec constructs in 6 mm cartilage defects, however, BioGlue. ®. showed significantly higher adhesive power. In vitro chondrogenesis of MSC under GDF-5 treatment resulted in equal GAG deposition and COLIIa1 and ACAN gene expression compared to controls. Importantly, significantly increased ALP-activity under treatment with GDF-5 on day 28 indicated enhanced hypertrophic differentiation compared to controls. In vivo, MSC-fibrin constructs pre-cultured with GDF-5 developed a significantly higher bone volume on day 14 and 28 compared to controls. When pre-cultured with GDF-5 constructs showed furthermore a significantly higher bone compactness (bone surface/bone volume coefficient) than controls, and thus revealed a higher maturity of the formed bone at 2 weeks and 4 weeks. Orthotopic biocompatibility testing in minipigs showed good defect filling and no adverse reactions of the subchondral bone plate for defects treated with GDF-5-augmented fibrin glue. Defects treated with BioGlue. ®. , however, showed considerable subchondral bone lysis. Thus, BioGlue. ®. – despite its adhesive strength – should not be used for construct fixation in cartilage defects. GDF-5-augmented fibrin glue is considered promising, because of a combination of the adhesive strength of fibrin with an enhanced osteochondral activity of GDF-5 on MSC. Next step is to perform a large animal study to unravel whether GDF-5 stimulated endochondral ossification can improve scaffold integration in an orthotopic cartilage defect model

Introduction. Osteoarthritis (OA), a painful, debilitating joint disease, often caused by excessive joint stress, is a leading cause of disability (World Health Organisation, 2003) and increases with age and obesity. A 5° varus malalignment increases loading in the medial knee compartment from 70% to 90% (Tetsworth and Paley, 1994). Internal unloading implants, placed subcutaneously upon the medial aspect of the knee joint, are designed to offload the medial compartment of the knee without violating natural joint tissues. The aim of this study is to investigate the effect of an unloading implant, such as the Atlas™ knee system, on stress within the tibiofemoral joint with different grades of cartilage defects. Methods. To simulate surgical treatment of medial knee OA, a three-dimensional computer-aided design of an Atlas™ knee system was virtually fixed to the medial aspect of a validated finite element knee model (Mootanah, 2014), using CATIA v5 software (Dassault Systèmes, Velizy Villacoublay, France). The construct was meshed and assigned material properties and boundary conditions, using Abaqus finite element software (Dassault Systèmes, Velizy Villacoublay, France). A cartilage defect was simulated by removing elements corresponding to 4.7 mm. 2. The international cartilage repair society (ICRS) Grade II and III damage were simulated by normalized defect depth of 33% and 67%, respectively. The femur was mechanically grounded and the tibia was subjected to loading conditions corresponding to the stance phase of walking of a healthy 50-year-old 68-Kg male with anthropometrics that matched those of the cadaver. Finite element analyses were run for peak shear and von Mises stress in the medial and lateral tibiofemoral compartments. Results. Von Mises stress distribution in the tibial cartilage, with ICRS Grade II and III defects, without the unloading implant, at the end of weight acceptance (15% of the gait cycle) were analysed. The internal unloading implant reduces peak von Mises stress by 40% and 43% for Grade II and Grade III cartilage defects, respectively. The corresponding reductions in shear stress are 36% and 40%. Consistent reduction in peak von Mises stress values in the medial cartilage-cartilage and cartilage-meniscus contact areas were predicted throughout the stance phase of the gait cycle for ICRS Grade II defect. Similar results were obtained for Grade III defect and for peak shear stress values. There were no overall increases in peak von Mises stress values in the lateral tibial cartilage. Discussion and Conclusions. The internal unloading implant is capable of reducing von Mises and shear stress values in the medial tibial cartilage with ICRS Grade II and III defects at the cartilage-cartilage and cartilage-meniscus interfaces throughout the stance phase of the gait cycle. This did not result in increased stress values in the lateral tibial cartilage. Our model did not account for the viscoelastic effects of the cartilage and meniscus. Results of this study are based on only one knee specimen. The internal unloading implant may protect the cartilage in individuals with medial knee osteoarthritis, thereby delaying the need for knee replacements

Abstract. Objectives. Bone marrow aspirate concentrate (BMAC), together with fibrin glue (Tisseel, Baxter, UK) and Hyaluronic acid (HA) were used as a one-step cell therapy treating patients with ankle cartilage defects in our hospital. This therapy was proven to be safe, with patients demonstrating a significant improvement 12 months post-treatment. Enriched mesenchymal stem cells (MSCs) in BMAC are suggested inducers of cartilage regeneration, however, currently there is no point-of-care assessment for BMAC quality; especially regarding the proportion of MSCs within. This study aims to characterise the cellular component of CCR-generated BMAC using a point-of-care device, and to investigate if the total nucleated cell (TNC) count and patient age are predictive of MSC concentration. Methods. During surgery, 35ml of bone marrow aspirate (BMA) was collected from each patients’ iliac crest under anaesthesia, and BMAC was obtained via a commercial kit (Cartilage Regeneration kit, CCR, Innotec. ®. , UK). BMAC was then mixed with thrombin (B+T) for injection with HA and fibrinogen. In our study, donor-matched BMA, BMAC and B+T were obtained from consented patients (n=12, age 41 ± 16years) undergoing surgery with BMAC therapy. TNC, red blood cell (RBC) and platelet (PLT) counts were measured via a haematology analyser (ABX Micros ES 60, Horiba, UK), and the proportion of MSCs in BMA, BMAC and B+T were assessed via colony forming unit-fibroblast (CFU-F) assays. Significant differences data in matched donors were tested using Friedman test. All data were shown as mean ± SD. Results. Mean TNC counts in BMA and BMAC were not significantly different (14.0 ± 4.4 million/ml and 19.4 ± 32.9 million/ml, respectively, P>0.9999). However, TNC counts were significantly lower in B+T compared to BMAC (9.7 ± 24.5 million/ml and 19.4 ± 32.9 million/ml, respectively, P=0.0167). Similarly, PLT counts were decreased in B+T compared to BMAC (40.7 ± 30.7 million/ml and 417.5 ± 365.5 million/ml, respectively, P<0.0001), however, PLTs were significantly concentrated in BMAC compared to BMA (417.5 ± 365.5 million/ml and 114.8 ± 61.6 million/ml, respectively, P=0.0429). RBC counts were significantly decreased in BMAC and B+T compared to BMA (P=0.0322 and P<0.0001, respectively). Higher concentration of MSCs were observed in BMAC compared to BMA (0.006% ± 0.01% and 0.00007% ± 0.0001%, respectively, P=0.0176). Similar to TNCs and PLTs, the proportion of MSCs significantly decreased in B+T compared to BMAC (0.0004% ± 0.001% and 0.006% ± 0.01%, respectively, P=0.0023). Furthermore, patient age and TNC counts did not correlate with MSC concentration (Spearman's Rank test, P=0.3266 and P=0.4880, respectively). Conclusions. BMAC successfully concentrated PLTs, but BMAC preparations were highly variable. Mixing BMAC and thrombin however, as described in the CCR protocol, resulted in a dramatic reduction in TNCs, PLTs and MSCs. TNC counts and patient age could not be used to predict the MSC proportion in the BMAC based on current data. Future work aims to look at the biomolecule profile of BMAC plasma, and to correlate them to patient clinical outcomes. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

In knee osteoarthritis (OA) patients, a focal cartilage defect is commonly found, especially in the medial compartment. In addition, cartilage softening is often observed at the defect rim. Both factors may alter the loading distribution and thereby the contact pressures, previously related to cartilage degeneration. To determine contact pressure in-vivo during motion, computational modelling can be used. The aim of this study was to analyse knee cartilage pressures during walking in healthy and damaged cartilage using a multi-scale modelling approach. Using 3D motion capture and musculoskeletal models, multi-body simulations of the stance phase of gait calculated knee kinematics and muscle, ligament and contact forces. These were subsequently imposed to a finite element (FE) model including tibial and femoral bones and cartilage. FE analyses were performed using intact cartilage as well as including a medial tibial cartilage defect, with and without softening of the defect rim. Specifically during loading response, a medial cartilage defect reduced the contact surface (−28%) and thereby increased the contact pressure (+33%) compared to intact cartilage, particularly on the medial compartment (+75% in contact pressure). Including softening of the cartilage rim increased the contact area (+22%) and decreased contact pressures (−9%) compared to the defect. This indicates that a focal defect increases the cartilage loading. This is partially compensated by softening of the cartilage rim. Therefore, the role of focal defects in altered cartilage loading and consequent OA development always needs to be discussed acknowledging the cartilage status at the defect rim

Over the last 10 years ACI (Autologous Chondrocyte Implantation) has become an important surgical technique for treating large cartilage defects. The original method has been improved by using cell seeded scaffolds for implantation. The aim of our prospective study was to evaluate the efficiency of a matrix based ACI (MACI) with a collagen type I scaffold for repairing large cartilage defects of the knee. We present the clinical and radiological results of 22 pts. one year after collagen scaffold based ACI. Out of 39 pts. treated with ACI for cartilage defects of the knee 22 had reached the one year follow up. We documented preoperatively and postoperatively (3, 6 and 12 months) the clinical situation with the IKDC Knee Examination Form. MRI scans were evaluated at all time points. 41% of the pts. were female, 59% male. The average age was 33 yrs. (min:15; max:49), the average BMI 25,4 (min:19; max:36). One third of the cartilage defects were localized retropatellar, the remaining on the medial or lateral femoral condyle. The average defect size was 5.7 cm2. In about 75% of the cases an additional surgical procedure was performed (ACL-reconstruction, lateral release, meniscal surgery). One major complication (a deep wound infection) occured. The IKDC score improved over time during follow up significantly. Patients with retropatellar defects have a poorer outcome compared to femoral defects. The MRI showed an improvement of the implanted scaffold over time as well. The present study confirms the benefits of MACI in young patients with large cartilage defects of the knee. The matrix based ACI is a surgically less demanding technique then the traditional ACI. We expect a good long term outcome from MACI comparable to that of traditional ACI

PURPOSE. Recently, in tissue engineering several methods using stem cells have been developed to repair chondral and osteochondral defects. Most of these methods rely on the use of scaffolds. Studies in the literature have demonstrated, first in animals and then in humans, that the use of mesenchymal stem cells withdrawn by several methods from adipose tissue allows to regenerate hyaline articular cartilage. In fact, it has been cleared that adipose-derived cells have multipotentiality equivalent to bone marrow-derived stem cells and that they can very easily and very quickly be isolated in large amounts enabling their immediate use in operating room for one-step cartilage repair techniques. The purpose of this study is to evaluate the therapeutic effect of adipose-derived stem cells on cartilage repair and present our experience in the treatment of knee cartilage defects by the novel AMIC REPAIR TECHNIQUE AUGMENTED by immersing the collagen scaffold with mesenchymal stem cells withdrawn from adipose tissue of the abdomen. MATERIALS AND METHODS. Fat tissue processing involves mechanical forces and does not mandatorily require any enzymatic or chemical treatment in order to obtain the regenerative cells from the lipoaspirate. In our study, mesenchymal adipose stem cells were obtained by non-enzymatic filtration or microfragmentation of lipoaspirates of the abdomen adipose tissue that enabled the separation of the stromal vascular fraction and were used in one-step reconstruction of knee cartilage defects by means of this new AUGMENTED AMIC TECHNIQUE. The focal defects underwent bone marrow stimulation microfractures, followed by coverage with collagen double layer resorbable membrane (Chondro-gide. TM. -Geistlich Pharma AG, Wolhusen, Switzerland) soaked in the cells obtained from fat in 18 patients, aged between 31 and 58 years, at the level of the left knee in 10 cases and in the right in eight, with follow-up ranging between 12 and 36 months. RESULTS: Surgical procedures have been completed without technical problems neither intraoperative or early postoperative complications. The evaluation scores (IKDC, KOOS and VAS) showed a significant improvement, more than 30%, at the initial 6 months follow-up and furtherly improved in the subsequent follow-ups. Also the control MRIs showed a progressive filling and maturation of the repair tissue of the defects. CONCLUSIONS. Since we are reporting a short and medium-term experience, it is not, of course, possible to provide conclusive assessment considerations on this technique, as the experience has to mature along with the progression of follow-ups. The simplicity together with the absence of intraoperative difficulties or immediate complications and the experience gained by other authors, first in animals and then in early clinical cases, makes it, however, possible to say that this can be considered one of the techniques to which resort for one-step treatment of cartilage defects in the knee because it improves patient's conditions and has the potential to regenerate hyaline-like cartilage. Future follow-up works will confirm the results

Healthy cartilage is essential for optimal joint function. Although, articular cartilage defects are highly prevalent in the active population and might hamper joint function, the effect of articular cartilage defects on knee contact forces and pressures is not yet documented. Therefore, the present study compared knee contact forces and pressures between patients with a tibiofemoral cartilage defect and healthy controls. This might provide additional insights in movement adaptations and the role of altered loading in the progression from defect to OA. Experimental gait data was collected in 15 patients with isolated articular cartilage defects (8 medial-affected, 7 lateral-affected) and 19 healthy asymptomatic controls and was processed using a musculoskeletal model to calculate contact forces and pressures. Differences between medial-affected, lateral-affected and controls were evaluated using Kruskal-Wallis tests and individually compared using Mann-Whitney-U tests (alpha <0.05). The lateral-affected group walked significantly slower compared to the healthy controls. No adaptations in the movement pattern that resulted in decreased loading on the injured condyle were observed. Additionally, the location of loading was not significantly affected. The current results suggest that isolated cartilage defects do not induce changes in the knee joint loading pattern. Consequently, the involved condyle will be equally loaded, indicating that a similar amount of force should be distributed over the remaining cartilage surrounding the articular cartilage defect and may cause local degenerative changes in the cartilage. This in combination with inflammatory responses might play a key role in the progression from articular cartilage defect to a more severe OA phenotype

Abstract. Objective. Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, these focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. Methods. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Nineteen studies were included in our review; four examined the use of human sMSCs and the remainder were conducted using sMSCs harvested from animals. Results. Despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures, all studies reported successful cartilage repair with sMSC transplantation. Conclusion. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high-quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Osteoarthritis is the most common chronic condition of the joints. It is characterized by the degeneration of articular cartilage, formation of osteophytes and alterations in the synovium. This process has a severe impact on the quality of life of the patients and the currently available treatments are unsatisfactory and often merely focused on pain relief. In our group we are working on the development of in situ cross-linkable hydrogel platforms that could be used for resurfacing the damaged articular cartilage using a minimally invasive arthroscopic procedure. Stable fixation of the gel at the joint surface, facilitating the ingrowth of local stem and progenitor cell populations and supporting intrinsic repair mechanisms are considered minimal design parameters. To achieve this, we are exploring the use of enzymatically cross-linkable natural polymer-tyramine conjugates. Dextran-tyramine conjugates were prepared by activation of dextran-OH and subsequent reaction with tyramine. Hyaluronic acid-tyramine and protein-tyramine conjugates were prepared using DMTMM coupling. In situ crosslinking is achieved by mixing the polymer conjugates with the enzyme HRP and minute, non-toxic amounts of H2O2 as oxidizing agent. Support of cartilage formation was studied after mixing of the polymer conjugates with mesenchymal stem cells, chondrocytes or combinations of both prior to crosslinking. Cell ingrowth was studied by implanting the hydrogels in an ex-vivo cartilage defect while mechanically loading the explant in a bioreactor and cell migration in the hydrogels was evaluated by tracking the sprouting of fluorescently labelled cell-spheroids. We prepared dextran-tyramine conjugates with a degree of substitution of 10 tyramine residues per 100 monosaccharide units. The conjugated hyaluronic acid-tyramine had a degree of substitution of 10% of the carboxylic acid groups, while for the proteins the substitution was dependent on the protein type. Enzymatically crosslinked hydrogels, based on dextran and hyaluronic acid, with the addition of co-cross linkable proteins show excellent properties for application in the regeneration of damaged cartilage

Cartilage is known to have limited intrinsic repair capabilities and cartilage defects can progress to osteoarthritis (OA). OA is a major economic burden of the 21st century, being among the leading causes of disability. The risk of disability from knee OA is as great as that derived from cardiovascular disease; a fact that becomes even more concerning when considering that even isolated cartilage defects can cause pain and disability comparable to that of severe OA. Several cartilage repair procedures are in current clinical application, including microfracture, osteochondral autograft transfer, osteochondral allograft transplantation, and autologous chondrocyte implantation (ACI). Given the economic challenges facing our health care system, it appears prudent to choose procedures that provide the most durable long-term outcome. Comparatively few studies have examined long-term outcomes, an important factor when considering the substantial differences in cost and morbidity among the various treatment options. This study reviews the clinical outcomes of autologous chondrocyte implantation at a minimum of 10 years after treatment of chondral defects of the knee. Mean age at surgery was 36 ± 9 years; mean defect size measured 8.4 ± 5.5cm2. Outcome scores were prospectively collected pre- and postoperatively at the last follow up. We further analyzed potential factors contributing to failure in hopes of refining the indications for this procedure. Conclusions: ACI provided durable outcomes with a survivorship of 71% at 10 years and improved function in 75% of patients with symptomatic cartilage defects of the knee at a minimum of 10 years after surgery. A history of prior marrow stimulation as well as the treatment of very large defects was associated with an increased risk of failure

Abstract. Objectives. The ability to predict which patients will improve following routine surgeries aimed at preventing the progression of osteoarthritis is needed to aid patients being stratified to receive the most appropriate treatment. This study aimed to investigate the potential of a panel of biomarkers for predicting (prior to treatment) the clinical outcome following treatment with microfracture or osteotomy. Methods. Proteins known to relate to OA severity, with predictive value in autologous cell implantation treatment or that had been identified in proteomic analyses (aggrecanase-1/ ADAMTS-4, cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), Lymphatic Vessel Endothelial Hyaluronan Receptor-1, matrix metalloproteinases-1 and −3, soluble CD14, S100 calcium binding protein A13 and 14-3-3 protein theta) were assessed in the synovial fluid (SF) of 19 and 13 patients prior to microfracture or osteotomy, respectively, using commercial immunoassays. Levels of COMP and HA were measured in the plasma of these patients. To find predictors of postoperative function, multiple linear regression analyses were performed. Results. Linear regression analyses demonstrated that a lower concentration of HA in pre-operative SF was predictive of improved knee function (higher Lysholm score) following microfracture surgery. Further, lower pre-operative activity of ADAMTS-4 in SF was a significant, independent predictor of higher post-operative Lysholm score (improved joint function) following osteotomy surgery. Conclusion. This study is novel in identifying biomarkers with the potential to predict clinical outcome in patients treated with microfracture or osteotomy of the knee. Lower concentrations of HA and undetectable activity of ADAMTS-4 in the joint fluid of individuals with cartilage defects/early-OA may be used in algorithms to stratify patients to the most appropriate surgery. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. Local cartilage defects in the knee are painful and mostly followed by arthritis. In order to avoid impaired mobility, the osteochondral defect might be bridged by a synthetic compound material: An osteoconductive titanium foam as an anchoring material in the subchondral bone and an infiltrated polymer as gliding material in contact with the surrounding natural cartilage. Materials and Methods. Titanium foam cylinders (Ø38 mm) with porosities ranging from 57% to 77% were produced by powder metallurgy with two different grain sizes of the space holder (fine: 340 ± 110 μm, coarse: 530 ± 160 μm). The sintered titanium foam cylinders were infiltrated with UHMWPE powder on one end and UHMWPE bulk at the other end, at two different temperatures (160 °C, 200 °C), using a pressure of 20 MPa for 15 minutes. Smaller cylinders (Ø16 mm) were retrieved from the compound material by water jet cutting. The infiltration depths were determined by optical microscopy. The anchoring of the UHMWPE was measured by a shear test and the mechanical properties of the titanium foam were verified by a subsequent compression test. The tribological behaviour was investigated in protein containing liquid using fresh cartilage pins (Ø5 mm) sliding against a UHMWPE disc with or without a notch to simulate the gap between the implant and the surrounding cartilage. Friction coefficients were determined in a rotation tribometer and the cartilage wear in a multidirectional six-station tribometer from AMTI (load 10 – 50 N, sliding speed 20 mm/s, 37 °C). Results. UHMWPE could be infiltrated into titanium foam by 1.1 – 1.3 mm with fine pores and by 1.5 – 1.8 mm with coarse pores. The infiltration was neither dependent on the type of UHMWPE (powder or bulk) nor on the temperature. The polymer was so well anchored inside the titanium foam pores that the shear forces for the compounds exceeded the shear strength obtained for a UHMWPE-cylinder. This effect was due to the increased stiffness of the compound plug. Uniaxial compression of the titanium foams after the shear-off of the polymer revealed yield strengths ranging from 50 – 88 MPa for porosities of 62 – 73%. The Ø16 mm samples yielded beyond physiological loads in the knee (≥ 10x body weight) and behaved in a strain hardening and fully ductile manner, reaching deformations of at least 50 % of their initial height without the appearance of macroscopically visible cracks. For smaller plug diameters down to Ø8 mm, however, the lower porosity / higher strength foam should be used to limit elastic deformation of the compound to < 0.1 mm. Pore size did not significantly influence the strength and stiffness values. The elevated coefficient of friction between cartilage and UHMWPE of about 1 was not negatively affected by the presence of the gap. The height loss of the cartilage pin after 1 hour (respectively after 3600 reciproque wear cycles) was 0.2 ± 0.1 mm using a flat disc. For discs with a 1 mm wide V-notch, the wear increased to 0.9 ± 0.3 mm. Conclusions. The tested titanium foams are well suited to act as an anchoring material in the subchondral bone as mechanical properties can be tailored by choosing the adequate porosity and as bone ingrowth has previously been demonstrated for the used pore sizes. UHMWPE is not an ideal gliding partner against cartilage because the friction coefficients of frictions were high. The presence of a V-notched gap was detrimental for cartilage wear. More hydrophilic polymers like PCU should be tested as potential gliding materials

Introduction: The debridement of deep cartilage defects is one of the most frequently used Methods: in arthroscopic surgery. This randomized study was undertaken to compare the effectiveness of simple mechanical debridement and the 52°C-controlled bipolar chondroplasty. Materials and Methods: A total of 60 patients (28 male, 32 female, average age 43.3 years, range 20 to 50 years) who were suffering from a grade III cartilage defect of the medial femoral condyle were included. Exclusion criteria were revision arthroscopy, injury or osteoarthritis (grade II or higher). After randomization, 30 patients underwent simple debridement of the cartilage defects, which was performed with a mechanical shaver (MSD = mechanical shaver debridement). The remaining patients underwent thermal chondroplasty, which was performed with a temperature-controlled bipolar device with a constant thermo-application of 51°C (RFC = Radio-Frequency-based Chondroplasty). The patients were evaluated by the Knee-injury and Osteoarthritis Outcome Score (KOSS) preoperatively and at time of follow-up. Activity levels were measured by the Tegner score (activity level before onset of the symptoms and at time of follow-up). Follow-up was undertaken 4 years after the arthroscopy. Results: No significant differences between the preoperative findings for the two groups were observed. One patient from the MSD group had died, and one female patient in the RFC group was lost to follow-up. A total of 18 patients had undergone revision operations due to persistent knee problems: in the MSD group, there were 8 endoprostheses, 4 osteotomies, and 2 revision arthroscopies; in the RFC group there was 1 one replacement, 2 osteotomies, and 1 revision arthroscopy with subtotal medial meniscectomy. The proportion of revisions was significantly higher in the MSD group (p=0.006). These patients were excluded from the evaluation. The remaining 40 patients from both groups benefited from the operation. The preoperative KOOS was 11.3 points in the MSD group and 15.5 points in the RFC group (p=0.279). Patients from the MSD group had a KOOS of 53.2 at the time of follow-up. In the RFC group the KOOS (71.8) was significantly higher (p< 0.001). Patients from both groups had to accept a decrease in their level of physical activity. However, patients from the RFC group had a significantly improved (p=0.005) Tegner activity score in comparison to the patients from the MSP group. The radiographic and MRI findings in the MSD group were also worse than in RFC patients. Conclusion: RFC is a potential method for the treatment of deep cartilage defects. The 4-year outcome is better than after MSD. Long-term results are still lacking

Abstract. Objective. Clinical treatments to repair articular cartilage (AC) defects such as autologous cartilage implantation (mosaicplasty) often suffer from poor integration with host tissue, limiting their long-term efficacy. Thus to ensure the longevity of AC repair, understanding natural repair mechanisms that allow for successful integration between cartilaginous surfaces, as has been reported in juvenile tissue, may be key. Here, we evaluated cartilage integration over time in a pig explant model of natural tissue repair by assessing expression and localisation of major ECM proteins, enzymatic cross-linkers including the five isoforms of lysyl oxidase (LOX), small leucine-rich repeat proteoglycans (SLRP's), and proteases (e.g. ADAMTS4). Methods. AC was retrieved from the femoral condyles of 8-week-old pigs. Full thickness 6mmØ AC discs were prepared, defects were induced, and explants cultured for up to 28 days. After fixation, sections were stained using Safranin-O and antibodies against Collagen types I & II, LOX, and ADAMTS4. Gene expression analyses were performed using qPCR. We also cultured devitalized samples, either with or without enzymatic treatment to deplete proteoglycans, for 28 days and similarly assessed repair. Results. Safranin-O staining demonstrated successful integration of cartilage defects over a 28-day period. No significant regulation in the expression of Col1a1, Col2a1, LOX or SLPR genes was observed at any time point. Immunofluorescence staining revealed that only ADAMTS4 localized at the injury surface in integrated samples. Interestingly, we also observed successful spontaneous integration of proteoglycan-depleted devitalized tissue. Conclusion. Cartilage integration in our pig cartilage explant model did not appear to be mediated by upregulation of major cartilage ECM components, enzymatic cross-linkers, or SLRPs. However, spontaneous integration of devitalized, proteoglycan-depleted AC, and localised upregulation of ADAMTS4 at the injured surface in successfully integrated samples, suggest that ADAMTS4 may enhances normal repair in injured AC through local aggrecan depletion, therefore enabling spontaneous cross-linking of collagen fibrils. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Objective. Full-thickness cartilage defects are commonly found in symptomatic knee patients, and are associated with progressive cartilage degeneration. Although the risk of defect progression to degenerative osteoarthritis is multifactorial, articular cartilage defects change contact mechanics and the mechanical response of tissue adjacent to the defect. The objective of this study was to quantify changes in intra-tissue strain patterns occurring at the defect rim and opposing tissue in an experimental model mimicking in vivo cartilage-on-cartilage contact conditions. Methods. Macroscopically intact osteochondral explants with smooth surfaces were harvested form the femoral condyles of 9 months old bovine knees. Two groups were tested; reference group with intact cartilage (n=8) and defect group with a full thickness cylindrical defect (diameter 8 mm) in one cartilage surface from each pair (n=8). The explants with defect articular surface and the opposing intact cartilage were compressed at ∼0.33 times body weight (350N) during cycles of 2s loading followed by 1.4s unloading. In plane tissue deformations were measured using displacement encoded imaging with stimulated echoes (DENSE) on a 9.4T MRI scanner. A two-sample t-test was used to assess statistical significance (p<0.05) of differences in maximal Green-Lagrange strains between the defect, opposing surface and intact reference cartilage. Results. Strain levels were elevated in the cartilage neighbouring the defect rim and in the opposing articulating surface. Similar to intact cartilage, compressive and tensile strains presented a depth dependent variation. The maximal strains profiles were highest in the superficial zone and decreased with depth for all explants, except for the shear strains in the cartilage opposing the defect which were constant. The maximal tensile strain in the middle and superficial zone were significantly higher for the defect cartilage (3.97±1.99% and 4.52±2.04%) compared to the intact reference (1.91±1.13% and 2.53±1.27%), indicating that the defect edges are bulging towards the defect. The shear strains were significantly higher (∼1.5x) throughout cartilage depth of the defect rim compared to the intact reference cartilage. However, in the cartilage opposing the defect, shear strains were significantly lower (∼0.5x) compared to the intact cartilage representing less matrix distortion. No significant difference in maximal compressive strains were observed between the opposing intact and defect at all cartilage depths. Conclusions. Presence of isolated full thickness cartilage defects will affect the cartilage deformations. Even under pure compressive loading alone, the altered contact mechanics resulted in excessive strains at tissue adjacent to the defect potentially damaging the cartilage and inducing tissue degeneration

The modified Hedgehog technique was previously used to reattach pure chondral shear-off fragments in the pediatric knee. In the modified Hedgehog technique, the calcified side of chondral fragments is multiple times incised and trimmed obliquely for an interlocking fit in the defect site. Fibrin glue with or without sutures is subsequently applied to fix the fragment to the defect. This preliminary report further elucidates the potential of the technique by evaluation of its application in young adults using patient reported outcome measures (PROMs) and high-field Magnetic Resonance Imaging (MRI) as outcome measures. Three patients with a femoral cartilage defect (2 medial, 1 lateral), and a concomitant pure chondral corpus liberum were operatively treated by the modified Hedgehog technique. Age at surgery ranged from 20.6–21.2 years, defect size ranged from 3.8–6.0 cm2. Patients were evaluated at three months and one year after surgery by PROMs and 7.0T MRI. PROMs included the Internation Knee Documentation (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale (VAS) questionnaires. 7.0T MRI (Magnetom, Siemens Healthcare, Erlangen, Germany) using a 28-channel proton knee coil (QED, Electrodynamics LLC, Cleveland, OH) included a proton density weighted turbo spin-echo sequence with fat suppression to assess morphological tissue structure andgagCEST imaging to measure the biochemical tissue composition in terms of glycosaminoglycans (GAG). Twelve months after surgery all patients reported no pain and showed full range of motion. While PROMs at three months showed large variability between patients, one year after surgery the scores were consistently improved. Over time, morphological MRI visualized improvements in integration of the cartilage fragment with the surrounding cartilage, which was supported by biochemical MRI showing increased GAG values at the defect edges. Statistics were not applied to the results because of the small sample size. The modified Hedgehog technique in young adults with an acute onset caused by a pure chondral corpus liberum can be considered promising. The improved PROM results over time were supported by 7.0T MRI that visualized improvements in tissue structure and biochemical composition. Inclusion of more patients in future studies would allow statistical analysis and more conclusive results. The etiology of loosening and time between onset of symptoms and surgery for successful graft integration may differ between pediatric and young adult patients and is subject for future studies

Hypothesis. Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate. The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than two years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms. Results. There were 522 defects in 321 patients (325 joints) treated with autologous chondrocyte implantation. On average, there were 1.7 lesions per patient. Of these joints, 111 had previously undergone surgery that penetrated the subchondral bone; 214 joints had no prior treatment that affected the subchondral bone and served as controls. Within the marrow stimulation group, there were 29 (26%) failures, compared with 17 (8%) failures in the control group. Conclusion. Defects that had prior treatment affecting the subchondral bone failed at a rate three times that of nontreated defects. The failure rates for drilling (28%), abrasion arthroplasty (27%), and microfracture (20%) were not significantly different—possibly because of the lower number of microfracture patients in this cohort (25 of 110 marrow-stimulation procedures). The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and, therefore, should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation. Unlike coventional wisdom, MSTs do ‘burn bridges’

Focal knee resurfacing implants (FKRIs) are typically intended to treat focal cartilage defects in middle-aged patients. All currently available FKRIs are (partly) composed of metal, which potentially leads to degeneration of the opposing articulating cartilage and hampers follow-up using magnetic resonance imaging (MRI). The purpose of this study was to investigate the in vivo osseointegration process of a novel non-degradable thermoplastic polycarbonate-urethane (TPU) osteochondral implant. Bi-layered implants measuring 6 mm in diameter, with a double-curvature to match the approximate curvature of the goat medial femoral condyle were fabricated. TPU implants were composed of an articulating Bionate® II 80A top layer, and a Bionate® 75D bottom layer (DSM Biomedical, Geleen, the Netherlands) which is intended to osseointegrate. A biphasic calcium phosphate coating formulation, optimized during a prior in vitro study, was applied to half of the TPU implants, while the other half was left uncoated. Bi-layered metal implants (articulating cobalt-chromium top layer and titanium bottom layer) were used as positive control implants. Eight implants per group were implanted bilaterally in the medial femoral condyle of the stifle joints in 12 Dutch milk goats. 18F-sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET-CT) scanning was performed at 3 and 12 weeks postoperatively, and the corrected maximum standard uptake values (cSUVmax) was calculated to assess the peri-implant bone metabolism. After sacrifice 12 weeks postoperatively, bone histomorphometric analysis was performed to assess the bone-to-implant contact area (BIC). Student's T-test was used in case of normal distribution and the Mann-Whitney-U-test was used in case of abnormal distribution for comparison of BIC and cSUVmax. The BIC value of 10.27 ± 4.50% (mean ± SD) for the BCP-coated TPU implants was significantly (P=0.03) higher than the 4.50 ± 2.61% for the uncoated TPU implants. The uncoated TPU implants scored significantly (P=0.04) lower than the BIC of 12.81 ± 7.55% for the metal implants, whereas there was no significant difference between BCP-coated TPU implants and the metal implants (P=0.68). There was a strong correlation between the cSUVmax values and the BIC values at 12 weeks (Pearson's R=0.74, P=0.001). The cSUVmax values significantly decreased between 3 and 12 weeks for the metal implants (p=0.04). BCP-coated TPU implants followed a similar trend but did not reach statistical significance (p=0.07). cSUVmax in the uncoated TPU implants did not show a significant difference between the time-points (p=0.31). Osseointegration of BCP-coated TPU implants did not significantly differ from metal implants. 18F-NaF PET-CT is a feasible modality to assess osseointegration patterns and showed a similar trend between the BCP-coated and metal implants. Hence, an implant fully composed of TPU may avoid the typical metal-related drawbacks of currently available FKRIs. Long-term follow-up studies are advocated to address the effects of the implant to the opposing cartilage, and are therefore warranted

Early detection of knee osteoarthritis (OA) is critical for possible preventive treatment, such as weight loss, physical activity and sports advice and restoring biomechanics, to postpone total knee arthroplasty (TKA). Specific biomarkers for prognosis and early diagnosis of OA are lacking. Therefore, in this study, we analyzed the lipid profiles of different tissue types within Hoffa's fat pad (HFP) of OA and cartilage defect (CD) patients, using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). The HFP has already been shown to play an important role in the inflammatory process in OA by prostaglandin release. Additionally, MALDI-MSI allows us to investigate on tissue lipid distribution at molecular level, which makes it a promising tool for the detection of disease specific biomarkers for OA development. Samples of HFP were obtained of patients undergoing surgical treatment for OA (n=3) (TKA) or CD (n=3) (cartilage repair). In all cases, tissue was obtained without patient harm. HFP samples were washed in phosphate buffered saline (PBS) and snap-frozen directly after surgical dissection to remove redundant blood contamination and to prevent as much tissue degradation as possible. Tissue sections were cut at 15 µm thickness in a cryostat (Leica Microsystems, Wetzlar) and deposited on indium tin oxide glass slides. Norharmane (Sigma-Aldrich) matrix was sublimed onto the tissue using the HTX Sublimator (HTX Technologies, Chapel Hill). µMALDI-MSI was performed using Synapt G2Si (Waters) at 50 µm resolution in positive ion mode. MS/MS fragmentation was performed for lipid identification. Data were processed with in-house Tricks for MATLAB and analyzed using principle component analysis (PCA) and verlan. OA and CD HFP specific lipid profiles were revealed by MALDI-MSI followed by PCA and DA. With these analyses we were able to distinguish different tissue types within HFP of different patient groups. Further discriminant analysis showed HFP intra-tissue heterogeneity with characteristic lipid profiles specific for connective and adipose tissues, but also for synovial tissue and blood vessels, revealing the high molecular complexity of this tissue. As expected, lipid signals were lower at the site of the connective tissue, compared to the adipose tissue. In particular, tri-acyl glycerol, di-acyl glycerol, sphingomyelin and phosphocholine species were differently abundant in the adipose tissue of HFP of OA compared to CD. To our knowledge, this is the first study comparing lipid profiles in HFP of OA patients with CD patients using MALDI-MSI. Our results show different lipid profiles between OA and CD patients, as well as intra-tissue heterogeneity within HFP, rendering MALDI-MSI as a useful technology for OA biomarker discovery. Future research will focus on expanding the number of subjects and the improvement of lipid detection signals

Autologous matrix-induced chondrogenesis (AMIC) is a new treatment option for full-thickness cartilage defect repair using the well-known microfracturing technique combined with a porcine collagen type I/III matrix implant and partially autologous fibrin sealant. A retrospective study has being carried out to investigate the objective and subjective clinical outcome of this procedure over a period of up to 2 years after the operation. 18 patients (10 male, 8 female) with localised cartilage defects were treated with AMIC. The mean age was 37 13 years. Defects treated were localised retropatellar (6), on the medial femoral condyle (7), on the lateral femoral condyle (2) and multiple lesions (3). During the clinical follow-up these patients were evaluated with the help of 3 different scores (IKDC score, Cincinnati score, Lysholm-Gillquist score). For the collective of 18 patients, one or more years had elapsed since the operation at the time this study was completed. 10 patients were included into the 2-year evaluation. The IKDC Score showed a mean improvement from 28 to 58 out of 100 at 1-year and from 25.5 to 69 out of 100 at 2-years post-operative. The Cincinnati and Lysholm-Gillquist scores showed the same tendency with an improvement of about 40 pecent at 1 year and about 55 percent at 2 years compared to pre-operative value. The improvement in the IKDC Score as well as the Cincinnati and Lysholm-Gillquist suggest that AMIC is a promising alternative in the treatment of local cartilage defects in the knee with good short and possibly mid-term results. Further follow up will reveal, if the good results are durable and AMIC, as matrix enhanced microfracturing technique can become a valuable, recognised cartilage repair technique

Ouery: Matrix-coupled autologous chondrocyte transplantation (MACT) has become increasingly widespread in the therapy of cartilage defects. The objective of this controlled prospective study was to examine the mid-term results of MACT compared to those of Microfracturing (MF) for the treatment of cartilage defects in the knee joint and to determine possible advantages or disadvantages of the two methods. Method: In order to compare the two treatment methods, 40 patients with discrete cartilage defects were treated with MACT and 40 with MF between 4/01 – 4/03. As inclusion criterion, the patients had a chondral defect of at least 1.5 cm and as exclusion criterion, there could be no additional cartilage damage in the other areas of the knee. MRI examinations were performed preoperative (T2 gew. TSE-Sequence, fetts. FLASH-3D) and could be repeated after 6 and 12 months. Knee joint function, the activity level and the patient’s quality of life were evaluated in both groups pre- and postoperative using the modified Cincinnati Score and the Tegner Activity Index. Results: There was significant improvement in the scores used for the study in both the MF group and the MACT group. Comparison of the two groups revealed significantly greater clinical improvement in the MACT patients than in the MF patients (3.8 point increase MACT versus 2.6 point increase MF in the Cincinnati Score). Taking the size extent of the treated cartilage damage into account, there was, however, no relevant difference in defects less than 2,5 qcm. Conclusion: The study could demonstrate that both methods are successful in treating localized cartilage damage in the knee joint. Comparison of the two forms of therapy showed a greater extent of improvement in the MACT group. However, classification by the size of the defect revealed that this effect was relevant only in larger defects, so that the size of the defect should be a decisive criterion for the selection of therapy

Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects. Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation (ACI). We present our experience with ACI after prior marrow stimulation. This study reviewed prospectively collected data for the first 321 consecutive patients treated at our institution with ACI for full-thickness cartilage defects that have reached more than 2 years of follow-up. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures due to persistent symptoms. This includes treatment with revision ACI, allograft transplantation, partial or total knee replacement. 522 defects in 321 patients (325 joints) were treated with ACI. Patient average age was 35 (13–60), there were 185 men and 136 women, with a follow-up of 2–12 Years. On average, there were 1.7 lesions per patient (range, 1–5) with a transplant area of 4.8 cm2 per lesion and 8.1 cm2 per knee. 111 of these joints had previously undergone surgery that penetrated the subchondral bone: microfracture (n=25), abrasion chondroplasty (n=33), and drilling (n=53). 214 joints had no prior treatment that affected the subchondral bone and served as control. Within the marrow stimulation group, there were 27 (24%) failures compared with 17 (8%) failures in the control group. In our review of 321 patients, defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of non-treated defects. These data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair, and should be used judiciously in larger cartilage defects that could require future treatment with ACI