Aims. The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects. Methods. HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks. Results. In vitro, the HAAM scaffolds had a network structure and possessed abundant collagen. The HAAM scaffolds had good cytocompatibility, and hAMSCs grew well on the HAAM scaffolds. In vivo, the macroscopic scores of the HAAM + JCFs group were significantly higher than those of the other groups. In addition, histological assessments demonstrated that large amounts of hyaline-like cartilage formed in the osteochondral defects in the HAAM + JCFs group. Integration with surrounding normal cartilage and regeneration of subchondral bone in the HAAM + JCFs group were better than those in the other groups. Conclusion. HAAM scaffolds combined with JCFs promote the regenerative repair of osteochondral defects. Cite this article: Bone Joint Res 2022;11(6):349–361

Objectives. We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Materials and Methods. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically. Results. At 16 weeks post-operatively, histological scores amongst treatment groups were not statistically different (TMPG: overall 12.7, cartilage 8.6, bone 4.1; TM: overall 14.2, cartilage 9.5, bone 4.9; ED: overall 13.6, cartilage 9.1, bone 4.5). Metal scaffolds were incorporated into the surrounding bone, both in TM and TMPG. The sGAG yield was lower in the neo-cartilage regions compared with the articular cartilage (AC) controls (TMPG 20.8/AC 39.5, TM 25.6/AC 33.3, ED 32.2/AC 40.2 µg sGAG/1 mg respectively), with statistical significance being achieved for the TMPG group (p < 0.05). Hypercellularity of the neo-cartilage was found in TM and ED, as the dsDNA content was significantly higher (p < 0.05) compared with contralateral AC controls (TM 126.7/AC 71.1, ED 99.3/AC 62.8 ng dsDNA/1 mg). The highest type II collagen content was found in neo-cartilage after TM compared with TMPG and ED (TM 60%/TMPG 40%/ED 39%). Inter-treatment differences were not significant. Conclusions. TM is a highly suitable material for the reconstitution of osseous defects. TM enables excellent bony ingrowth and fast integration. However, combined with autologous periosteum, such a biocomposite failed to promote satisfactory neo-cartilage formation. Cite this article: E. H. Mrosek, H-W. Chung, J. S. Fitzsimmons, S. W. O’Driscoll, G. G. Reinholz, J. C. Schagemann. Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. Bone Joint J 2016;5:403–411. DOI: 10.1302/2046-3758.59.BJR-2016-0070.R1

Aims. Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. Methods. The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. Results. The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. Conclusion. Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677–689

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p < 0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors

Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 (. sd. 0) to a mean of 1.9 (. sd. 0.3) and the ‘Matrix’ score from a mean of 3.0 (. sd. 0) to a mean of 2.5 (. sd. 0.5). This progressed further at T3, with the International Cartilage Repair Society ‘Surface’ grading, the ‘Matrix’ grading, ‘Cell Distribution’ and ‘Cell Viability’ grading further decreasing and the Mankin score rising from a mean of 1.3 (. sd. 1.4) to a mean of 5.1 (. sd. 1.6). Human biopsies achieved Mankin grading of a mean of 4.2 (. sd. 1.6) and were comparable with the ovine histology at T1 and T3. The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined. The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment

We reviewed, retrospectively, 13 patients who had undergone open anterograde autologous bone grafting of the talus for symptomatic osteochondral defects of the dome of the talus. The mean age of the seven men and six women was 38.4 years. The defects included the full thickness of articular cartilage, extended through the subchondral plate and were associated with subchondral cysts. Six patients (46%) were clinical failures requiring further surgery. Of the remaining seven, functional outcome results were obtained at a mean of 51.9 months after surgery. The mean outcome scores for the Musculoskeletal Outcomes Data Evaluation and Management System foot and ankle questionnaire and the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale were 87.0 and 84.3, respectively. There was an overall 46.2% patient satisfaction rate. We believe that the technique of autologous bone grafting presented should be used with extreme caution, when considered as the primary treatment for the adult patient with a symptomatic advanced osteochondral defect of the talus

We describe a new method of biological repair of osteochondral defects. In rabbit knees an osteochondral defect was reconstructed with a callo-osseous graft made of a superficial sheet of medullary fracture callus attached to a base of cancellous bone. This was taken from the iliac bone of the same animal which had been osteotomised ten days earlier. The reparative tissues were evaluated for 24 weeks by quantitative histology, biochemical analysis of the uronic acid content, and immunohistochemical staining of collagen constituents. The callo-osseous graft provided significantly faster and better repair of the articular surface than an untreated defect or a callo-osseous graft in which the cells had been devitalised by irradiation before transplantation. Our findings indicate that the callo-osseous graft contributes to the repair process by providing both favourable extracellular matrices and pluripotential mesenchymal cells. Our study tested the hypothesis that early medullary callus generates hyaline cartilage instead of bone after transfer to an articular surface

We have evaluated the clinical effectiveness of a metal resurfacing inlay implant for osteochondral defects of the medial talar dome after failed previous surgical treatment. We prospectively studied 20 consecutive patients with a mean age of 38 years (20 to 60), for a mean of three years (2 to 5) post-surgery. There was statistically significant reduction of pain in each of four situations (i.e., rest, walking, stair climbing and running; p ≤ 0.01). The median American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from 62 (interquartile range (IQR) 46 to 72) pre-operatively to 87 (IQR 75 to 95) at final follow-up (p < 0.001). The Foot and Ankle Outcome Score improved on all subscales (p ≤ 0.03). The mean Short-Form 36 physical component scale improved from 36 (23 to 50) pre-operatively to 45 (29 to 55) at final follow-up (p = 0.001); the mental component scale did not change significantly. On radiographs, progressive degenerative changes of the opposing tibial plafond were observed in two patients. One patient required additional surgery for the osteochondral defect. This study shows that a metal implant is a promising treatment for osteochondral defects of the medial talar dome after failed previous surgery. Cite this article: Bone Joint J 2013;95-B:1650–5

Autologous chondrocyte implantation (ACI) is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted

Objectives. The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. Methods. The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. Results. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. Conclusion. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56–64

We reviewed 38 patients who had been treated for anosteochondral defect of the talus by arthroscopic curettage and drilling. The indication for surgical treatment was persistent symptoms after conservative treatment for at least six months. A total of 22 patients had received primary surgical treatment (primary group) and 16 had had failed previous surgery (revision group). The mean follow-up was 4.8 years (2 to 11). Good or excellent results, as assessed by the Ogilvie-Harris score, were found in 86% in the primary group and in 75% in the revision group. Two further procedures were required, one in each group. Radiological degenerative changes were seen in one ankle in the revision group after ten years. Arthroscopic curettage and drilling are recommended for both primary and revision treatment of an osteochondral defect of the talus

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis.

All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage.

Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.

Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm². The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26).

Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed.

Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value.

Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect.

Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect.

The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm.

The management of failed autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI) for the treatment of symptomatic osteochondral defects in the knee represents a major challenge. Patients are young, active and usually unsuitable for prosthetic replacement. This study reports the results in patients who underwent revision cartilage transplantation of their original ACI/MACI graft for clinical or graft-related failure. We assessed 22 patients (12 men and 10 women) with a mean age of 37.4 years (18 to 48) at a mean of 5.4 years (1.3 to 10.9). The mean period between primary and revision grafting was 46.1 months (7 to 89). The mean defect size was 446.6 mm. 2. (150 to 875) and they were located on 11 medial and two lateral femoral condyles, eight patellae and one trochlea. . The mean modified Cincinnati knee score improved from 40.5 (16 to 77) pre-operatively to 64.9 (8 to 94) at their most recent review (p < 0.001). The visual analogue pain score improved from 6.1 (3 to 9) to 4.7 (0 to 10) (p = 0.042). A total of 14 patients (63%) reported an ‘excellent’ (n = 6) or ‘good’ (n = 8) clinical outcome, 5 ‘fair’ and one ‘poor’ outcome. Two patients underwent patellofemoral joint replacement. This study demonstrates that revision cartilage transplantation after primary ACI and MACI can yield acceptable functional results and continue to preserve the joint. Cite this article: Bone Joint J 2014;96-B:54–8

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. Methods. A bilateral osteochondral defect was created in the femoral trochlear groove of 14 New Zealand white rabbits. The right knees were filled with PRP gel and the contralateral knees remained untreated and served as control sides. Some animals were killed at week 3 and others at week 12 postoperatively. The joints were harvested and assessed by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) MRI scoring system, and examined using the International Cartilage Repair Society (ICRS) macroscopic and ICRS histological scoring systems. Additionally, the collagen type II content was evaluated by the immunohistochemical staining. Results. After 12 weeks post-surgery, the defects of the PRP group were repaired by hyaline cartilage-like tissue. However, incomplete cartilage regeneration was observed in the PRP group for three weeks. The control groups showed fibrocartilaginous or fibrous tissue, respectively, at each timepoint. Conclusion. Our study proved that the use of PRP gel without any adjuncts could successfully produce a good healing response and resurface the osteochondral defect with a better quality of cartilage in a rabbit model. Cite this article: Bone Joint Res 2021;10(3):192–202

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887

Objectives. Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (. sd. ) and compared at different time points between the two groups using the Mann-Whitney U test, with a value < 0.05 considered statistically significant. Results. Higher cumulative macroscopic and histological scores were observed in stem cell treated defects throughout the study period with significant differences noted at four and 24 weeks (9.25, . sd. 0.5 vs 7.25, . sd. 0.95, and 10, . sd. 0.81 vs 7.5, . sd. 0.57; p < 0.05) and 16 weeks (16.5, . sd. 4.04 vs 11, . sd. 1.15; p < 0.05), respectively. Superior gross and histological characteristics were also observed in stem cell treated defects. Conclusion. The use of autologous culture expanded bone marrow derived mesenchymal stem cells on platelet rich fibrin is a novel method for articular cartilage regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017;6:98–107. DOI: 10.1302/2046-3758.62.BJR-2016-0188.R1

Aims. Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Methods. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining. Results. In vitro testing showed that the secreted ECM oriented itself along the fibre in multi-layered scaffolds. Both types of CG scaffolds supported cell viability, growth, and matrix synthesis. In vitro chondrogenesis on scaffold showed an around 400-fold increase in collagen type 2 (COL2A1) expression in both CG scaffolds, but the total glycosaminoglycan (GAG)/DNA deposition was 1.39-fold higher in the multi-layered scaffold than the randomly aligned scaffold. In vivo cartilage formation occurred in both multi-layered and randomly aligned scaffolds treated with and without cells, and was shown to be of hyaline phenotype on immunostaining. The defects treated with multi-layered + cells, however, showed significantly thicker cartilage formation than the randomly aligned scaffold. Conclusion. We demonstrated that MSCs loaded CG scaffold with multi-layered zonal architecture promoted superior hyaline AC regeneration. Cite this article: Bone Joint Res 2020;9(9):601–612

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson’s ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique

The December 2012 Foot & ankle Roundup. 360. looks at: correcting the overcorrected club foot; syndesmotic surgery; autograft for osteochondral defects; sesamoidectomy after fracture in athletes; complications in ankle replacement; the arthroscope as a treatment for ankle osteoarthritis; whether da Vinci was a modern foot surgeon; and a popliteal block in ankle fixation

The February 2013 Knee Roundup. 360 . looks at: mobile-bearing TKRs; arthroscopic ACL reconstruction; the use of chondrocytes for osteochondral defects; ACL reconstruction and the return to pivoting sports; ACLs and the MOON study; the benefit of knee navigation; and trabecular metal

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

Chondral damage to the knee is common and, if left untreated, can proceed to degenerative osteoarthritis. In symptomatic patients established methods of management rely on the formation of fibrocartilage which has poor resistance to shear forces. The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect. Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and debilitating with the aim of replacing damaged cartilage with hyaline or hyaline-like cartilage, leading to improved function. The intermediate and long-term functional and clinical results are promising. We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution with a mean follow-up of 32 months (1 to 9 years). The procedure is shown to offer statistically significant improvement with advantages over other methods of management of chondral defects

We investigated the prognostic indicators for collagen-covered autologous chondrocyte implantation (ACI-C) performed for symptomatic osteochondral defects of the knee. We analysed prospectively 199 patients for up to four years after surgery using the modified Cincinnati score. Arthroscopic assessment and biopsy of the neocartilage was also performed whenever possible. The favourable factors for ACI-C include younger patients with higher pre-operative modified Cincinnati scores, a less than two-year history of symptoms, a single defect, a defect on the trochlea or lateral femoral condyle and patients with fewer than two previous procedures on the index knee. Revision ACI-C in patients with previous ACI and mosaicplasties which had failed produced significantly inferior clinical results. Gender (p = 0.20) and the size of the defect (p = 0.97) did not significantly influence the outcome

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 used fresh small-fragment osteochondral allografts to reconstruct post-traumatic osteochondral defects in 126 knees of 123 patients with a mean age of 35 years. At a mean follow-up of 7.5 years (2 to 20), 108 knees were rated as successful (85%) and 18 had failed (15%). The factors related to failure included age over 50 years (p = 0.008), bipolar defects (p < 0.05), malaligned knees with overstressing of the grafts, and workers’ compensation cases (p < 0.04). Collapse of the graft by more than 3 mm and of the joint space of more than 50% were seen more frequently in radiographs of failed grafts. Our encouraging clinical results for fresh small-fragment osteochondral allografts show that they are indicated for unipolar post-traumatic osteochondral defects of the knee in young active patients

Autologous chondrocyte implantation is an established method of treatment for symptomatic articular defects of cartilage. CARTIPATCH is a monolayer-expanded cartilage cell product which is combined with a novel hydrogel to improve cell phenotypic stability and ease of surgical handling. Our aim in this prospective, multicentre study on 17 patients was to investigate the clinical, radiological, arthroscopic and histological outcome at a minimum follow-up of two years after the implantation of autologous chondrocytes embedded in a three-dimensional alginate-agarose hydrogel for the treatment of chondral and osteochondral defects. Clinically, all the patients improved significantly. Patients with lesions larger than 3 cm. 2. improved significantly more than those with smaller lesions. There was no correlation between the clinical outcome and the body mass index, age, duration of symptoms and location of the defects. The mean arthroscopic International Cartilage Repair Society score was 10 (5 to 12) of a maximum of 12. Predominantly hyaline cartilage was seen in eight of the 13 patients (62%) who had follow-up biopsies. Our findings suggest that autologous chondrocyte implantation in combination with a novel hydrogel results in a significant clinical improvement at follow-up at two years, more so for larger and deeper lesions. The surgical procedure is uncomplicated, and predominantly hyaline cartilage-like repair tissue was observed in eight patients

Aims

Hyaline cartilage has a low capacity for regeneration. Untreated osteochondral lesions of the femoral head can lead to progressive and symptomatic osteoarthritis of the hip. The purpose of this study is to analyze the clinical and radiological long-term outcome of patients treated with osteochondral autograft transfer. To our knowledge, this study represents a series of osteochondral autograft transfer of the hip with the longest follow-up.

The April 2024 Foot & Ankle Roundup³⁶⁰ looks at: Safety of arthroscopy combined with radial extracorporeal shockwave therapy for osteochondritis of the talus; Bipolar allograft transplantation of the ankle; Identifying risk factors for osteonecrosis after talar fracture; Balancing act: immediate versus delayed weightbearing in ankle fracture recovery; Levelling the field: proximal supination osteotomy’s efficacy in severe and super-severe hallux valgus; Restoring balance: how adjusting the tibiotalar joint line influences movement after ankle surgery.

Aims

Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

Aims

The outcomes following nonoperative management of minimally displaced greater tuberosity (GT) fractures, and the factors which influence patient experience, remain poorly defined. We assessed the early patient-derived outcomes following these injuries and examined the effect of a range of demographic- and injury-related variables on these outcomes.

Aims

The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process.

Aims

This scoping review aims to identify patient-related factors associated with a poorer outcome following total ankle arthroplasty (TAA).

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

We assessed the use of woven carbon fibre pads to resurface osteochondral defects in animals and in patients. The pads became filled with structurally strong and compliant fibrous tissue and did not provoke a synovial reaction, though pigmentation was induced in some animals. Of the patients, 77% had a satisfactory response to resurfacing, with no synovitis. Our initial experiments indicate that carbon pads may provide a satisfactory treatment for localised articular defects

The February 2023 Hip & Pelvis Roundup³⁶⁰ looks at: Total hip arthroplasty or internal fixation for hip fracture?; Significant deterioration in quality of life and increased frailty in patients waiting more than six months for total hip or knee arthroplasty: a cross-sectional multicentre study; Long-term cognitive trajectory after total joint arthroplasty; Costal cartilage grafting for a large osteochondral lesion of the femoral head; Foley catheters not a problem in the short term; Revision hips still a mortality burden?; How to position implants with a robotic arm; Uncemented stems in hip fracture?

The December 2022 Hip & Pelvis Roundup³⁶⁰ looks at: Fix and replace: simultaneous fracture fixation and hip arthroplasty for acetabular fractures in older patients; Is the revision rate for femoral neck fracture lower for total hip arthroplasty than for hemiarthroplasty?; Femoral periprosthetic fractures: data from the COMPOSE cohort study; Dual-mobility cups and fracture of the femur; What’s the deal with outcomes for hip and knee arthroplasty outcomes internationally?; Osteochondral lesions of the femoral head: is costal cartilage the answer?

Aims

The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach.

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

We describe a prospective study of 328 patients undergoing arthroscopy of the hip. Arthrography, CT or MRI was performed when clinically indicated. A preoperative diagnosis was reached in 174 patients (53%), while the remaining 154 were diagnosed as having ‘idiopathic hip pain’. In seven patients, access to the hip was inadequate. Arthroscopy altered the diagnosis in 176 hips (53%). The new primary diagnoses were osteoarthritis (75 patients), osteochondral defects (34), torn labra (23), synovitis (11) and loose bodies (9). In 172 hips (52%) an operative procedure was undertaken. In the remaining 84 patients (26%), arthroscopy neither changed the diagnosis nor provided surgical treatment. Arthroscopy of the hip is considered to be of value in assessing and treating the adult patient with pain in the hip of uncertain cause

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

Fresh osteochondral allografts were used to repair post-traumatic osteoarticular defects in 92 knees. At the time of grafting, varus or valgus deformities were corrected by upper tibial or supracondylar femoral osteotomies. A survivorship analysis was performed in which failure was defined as the need for a revision operation or the persistence of the pre-operative symptoms. There was a 75% success rate at five years, 64% at ten years and 63% at 14 years. The failure rate was higher for bipolar grafts than for unipolar and the results in patients over the age of 60 years were poor. The outcome did not depend on the sex of the patient and the results of allografts in the medial and lateral compartments of the knee were similar. Careful patient selection, correction of joint malalignment by osteotomy, and rigid fixation of the graft are all mandatory requirements for success. We recommend this method for the treatment of post-traumatic osteochondral defects in the knees of relatively young and active patients

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