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1.  Establishing proof of concept: Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus 
World Journal of Orthopedics  2012;3(7):101-108.
Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative (microfracture) or replacement (autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration, with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.
doi:10.5312/wjo.v3.i7.101
PMCID: PMC3399015  PMID: 22816065
Osteochondral lesion; Cartilage repair; Platelet-rich plasma; Bone marrow aspirate concentrate
2.  Treatment of Focal Articular Cartilage Defects in the Knee 
We asked whether autologous chondrocyte implantation or osteochondral autograft transfer yields better clinical outcomes compared with one another or with traditional abrasive techniques for treatment of isolated articular cartilage defects and whether lesion size influences this clinical outcome. We performed a literature search and identified five randomized, controlled trials and one prospective comparative trial evaluating these treatment techniques in 421 patients. The operative procedures included autologous chondrocyte implantation, osteochondral autograft transfer, matrix-induced autologous chondrocyte implantation, and microfracture. Minimum followup was 1 year (mean, 1.7 years; range, 1–3 years). All studies documented greater than 95% followup for clinical outcome measures. No technique consistently had superior results compared with the others. Outcomes for microfracture tended to be worse in larger lesions. All studies reported improvement in clinical outcome measures in all treatment groups when compared with preoperative assessment; however, no control (nonoperative) groups were used in any of the studies. A large prospective trial investigating these techniques with the addition of a control group would be the best way to definitively address the clinical questions.
Level of Evidence: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-007-0097-z
PMCID: PMC2504649  PMID: 18196358
3.  Osteochondral lesion of the talus in a recreational athlete: a case report 
A 23-year-old recreational male athlete presented with intermittent pain of three weeks duration, localized to the left ankle. Pain was aggravated by walking, although his symptoms had not affected the patient’s jogging activity which was performed three times per week. Past history revealed an inversion sprain of the left ankle, sustained fifteen months previously. Examination showed mild swelling anterior to the ankle mortise joint while other tests including range of motion, strength and motion palpation of specific joints of the ankle were noted to be unremarkable. Radiographic findings revealed a defect in the medial aspect of the talus. An orthopaedic referral was made for further evaluation. Tomography revealed a Grade III osteochondral lesion of the talus.
It was determined that follow-up views be taken in three months to demonstrate if the lesion was progressing or healing. Within the three month period, activity modifications and modalities for pain control were indicated. Surgery was considered a reasonable option should conservative measures fail.
The present case illustrates an osteochondral lesion of the talus, a condition which has not previously been reported in the chiropractic literature. A review of the pertinent orthopaedic literature has indicated an average delay of three years in diagnosing the existence of this lesion.
Although considered rare, the diagnostic frequency of the condition appears to be on the rise due to increased awareness and the use of bone and CT scans. The osteochondral lesion of the talus deserves particular consideration by practitioners working with athletes due to its higher incidence within this group. This diagnosis should be considered in patients presenting with chronic ankle pain particularly when a history of an inversion sprain exists.
The purpose of this report is to increase awareness of this condition, and review diagnosis and management strategies.
Images
PMCID: PMC2485432
osteochondral lesion; talus; osteochondritis dissecans; diagnosis; chiropractic; athletic injuries; ankle
4.  Total ankle replacement in rheumatoid arthritis 
International Orthopaedics  2003;28(2):123-126.
We reviewed 21 patients with rheumatoid arthritis who had a total ankle replacement between 1984 and 2000. The average follow-up was 72 (15–169) months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. At the latest review, three ankles had been revised. Two ankles were excellent, seven good, three fair, and 12 poor. Eleven patients with 13 ankles had residual pain, with radiographs showing a high incidence of radiolucent lines. Migration of the tibial component was seen in 13 ankles and collapse of talus in nine. Although clinical results were poor, patient satisfaction was not.
doi:10.1007/s00264-003-0512-3
PMCID: PMC3474485  PMID: 15224171
5.  Treatment of osteochondritis dissecans of the femoral condyle with autologous bone grafts and matrix-supported autologous chondrocytes 
International Orthopaedics  2009;34(6):819-825.
The objective of this study was to determine the clinical outcome of combined bone grafting and matrix-supported autologous chondrocyte transplantation in patients with osteochondritis dissecans of the knee. Between January 2003 and March 2005, 21 patients (mean age 29.33 years) with symptomatic osteochondritis dissecans (OCD) of the medial or lateral condyle (grade III or IV) of the knee underwent reconstruction of the joint surface by autologous bone grafts and matrix-supported autologous chondrocyte transplantation. Patients were followed up at three, six, 12 and 36 months to determine outcomes by clinical evaluation based on Lysholm score, IKDC and ICRS score. Clinical results showed a significant improvement of Lysholm-score and IKDC score. With respect to clinical assessment, 18 of 21 patients showed good or excellent results 36 months postoperatively. Our study suggests that treatment of OCD with autologous bone grafts and matrix-supported autologous chondrocytes is a possible alternative to osteochondral cylinder transfer or conventional ACT.
doi:10.1007/s00264-009-0841-y
PMCID: PMC2989013  PMID: 19626325
6.  Treatment of osteochondral lesions of the talus: a systematic review 
The aim of this study was to summarize all eligible studies to compare the effectiveness of treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from January 1966 to December 2006 were systematically screened. The proportion of the patient population treated successfully was noted, and percentages were calculated. For each treatment strategy, study size weighted success rates were calculated. Fifty-two studies described the results of 65 treatment groups of treatment strategies for OCD of the talus. One randomized clinical trial was identified. Seven studies described the results of non-operative treatment, 4 of excision, 13 of excision and curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an autogenous bone graft, 2 of transmalleolar drilling (TMD), 9 of osteochondral transplantation (OATS), 4 of autologous chondrocyte implantation (ACI), 3 of retrograde drilling and 1 of fixation. OATS, BMS and ACI scored success rates of 87, 85 and 76%, respectively. Retrograde drilling and fixation scored 88 and 89%, respectively. Together with the newer techniques OATS and ACI, BMS was identified as an effective treatment strategy for OCD of the talus. Because of the relatively high cost of ACI and the knee morbidity seen in OATS, we conclude that BMS is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus.
doi:10.1007/s00167-009-0942-6
PMCID: PMC2809940  PMID: 19859695
Ankle; Osteochondral lesion; Defect; Talus; Systematic review; Arthroscopy
7.  Intra-articular Lesions in Chronic Lateral Ankle Instability: Comparison of Arthroscopy with Magnetic Resonance Imaging Findings 
Clinics in Orthopedic Surgery  2012;4(4):293-299.
Background
Chronic lateral ankle instability often accompanies intra-articular lesions, and arthroscopy is often useful in diagnosis and treatment of intra-articular lesions.
Methods
Preoperative magnetic resonance imaging (MRI) examinations and arthroscopic findings were reviewed retrospectively and compared in 65 patients who underwent surgery for chronic lateral ankle instability from January 2006 to January 2010. MR images obtained were assessed by two radiologists, and the inter- and intra-observer reliability was calculated. American Orthopedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) scores were evaluated.
Results
Abnormalities of the anterior talofibular ligament (ATFL) were found in all 65 (100%) cases. In arthroscopy examinations, 33 (51%) cases had talar cartilage lesions, and 3 (5%) cases had 'tram-track' cartilage lesion. Additionally, 39 (60%) cases of synovitis, 9 (14%) cases of anterior impingement syndrome caused by osteophyte, 14 (22%) cases of impingement syndrome caused by fibrotic band and tissue were found. Sensitivity of MRI examination for each abnormality was: ATFL, 60%; osteochondral lesion of talus (OLT), 46%; syndesmosis injury, 21%; synovitis, 21%; anterior impingement syndrome caused by osteophyte, 22%. Paired intra-observer reliability was measured by a kappa statistic of 0.787 (95% confidence interval [CI], 0.641 to 0.864) for ATFL injury, 0.818 (95% CI, 0.743 to 0.908) for OLT, 0.713 (95% CI, 0.605 to 0.821) for synovitis, and 0.739 (95% CI, 0.642 to 0.817) for impingement. Paired inter-observer reliability was measured by a kappa statistic of 0.381 (95% CI, 0.241 to 0.463) for ATFL injury, 0.613 (95% CI, 0.541 to 0.721) for OLT, 0.324 (95% CI, 0.217 to 0.441) for synovitis, and 0.394 (95% CI, 0.249 to 0.471) for impingement. Mean AOFAS score increased from 64.5 to 87.92 (p < 0.001) when there was no intra-articular lesion, from 61.07 to 89.04 (p < 0.001) in patients who had one intra-articular lesion, and from 61.12 to 87.6 (p < 0.001) in patients who had more than two intra-articular lesions.
Conclusions
Although intra-articular lesion in patients with chronic lateral ankle instability is usually diagnosed with MRI, its sensitivity and inter-observer reliability are low. Therefore, arthroscopic examination is strongly recommended because it improved patients' residual symptoms and significantly increased patient satisfaction.
doi:10.4055/cios.2012.4.4.293
PMCID: PMC3504694  PMID: 23205239
Chronic lateral ankle instability; Arthroscopy; Magnetic resonance imaging
8.  Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel 
Purpose
Severe symptomatic and unstable osteochondral defects of the knee are difficult to treat. A variety of surgical techniques have been developed. However, the optimal surgical technique is still controversial. We present a novel technique in which autologous bone grafting is combined with gel-type autologous chondrocyte implantation (GACI).
Methods
Isolated severe osteochondral defects of the medial or lateral femoral condyle were treated by a two-step procedure. Firstly, chondrocytes were harvested during arthroscopy and cultured for 6 weeks. Secondly, a full thickness corticospongious autologuos bone graft, harvested from the medial or lateral femur condyle, is impacted in the defect and covered by GACI. The fibrin gel fills up to the exact shape of the chondral lesion and polymerizes within 3 min after application.
Results
From 2009 to 2011, 9 patients, median age 35 years (range 23–47), were treated by the combined autologous bone grafting and GACI technique. Median defect size was 7.1 cm2 (range 2.5–12.0), and median depth of the lesion was 0.9 cm (range 0.8–1.2). Median follow-up was 9 months (range 6–12 months). Six patients were available for 12-month follow-up. The mean IKDC score showed a 6-month improvement from 35 (SD ± 16) to 51 (SD ± 18) (n = 9; p = 0.01), and a 1-year improvement from 35 (SD ± 16) to 57 (SD ± 20) (n = 6; p = 0.03). The mean KOOS improved from 44 (SD ± 16) to 62 (SD ± 19) (n = 9; p = 0.07) at 6-month follow-up and from 44 (SD ± 16) to 65 (SD ± 24) (n = 6; p = 0.1) at 12-month follow-up. There was one failure that needed conversion to a unicompartmental knee arthroplasty.
Conclusion
Combined autologous bone grafting and GACI may offer an alternative surgical option for severe and unstable osteochondral defects of the knee.
Level of evidence
IV.
doi:10.1007/s00167-012-1891-z
PMCID: PMC3477477  PMID: 22302036
Osteochondral defect; Knee; Bone graft; Fibrin gel; ACI
9.  Management of cartilage defects in the shoulder 
Articular cartilage lesions of the glenohumeral joint are an especially difficult clinical problem to manage, particularly in the younger, more active patient. Left untreated, these lesions may progress in the long-term, leading to further pain and disability. While shoulder arthroplasty remains a viable option in older patients with glenohumeral arthritis, concerns over component longevity and loosening in younger patients make it less attractive in that age group. Arthroscopic joint debridement with loose body removal, often with capsular release, has been successful in select, more sedentary patients. More recent techniques, including autologous chondrocyte implantation (ACI), osteochondral grafting (allograft versus autograft), interpositional arthroplasty, and microfracture surgery, have been evaluated for use in the shoulder. These procedures have experienced success in weight bearing joints, including the knee and ankle. Despite the good clinical results in the shoulder with short-term follow-up reported in some small series, the treatment of chondral injuries in the glenohumeral joint remains a challenging problem.
doi:10.1007/s12178-012-9131-1
PMCID: PMC3535081  PMID: 22628177
Glenohumeral arthritis; Microfracture; Autogenous chondrocyte transfer; Osteochondral graft; Interpositional arthroplasty; Sports non-ACL
10.  The subchondral bone in articular cartilage repair: current problems in the surgical management 
As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed.
doi:10.1007/s00167-010-1072-x
PMCID: PMC2839476  PMID: 20130833
Cartilage repair; Autologous chondrocyte implantation; Microfracture; Subchondral bone
11.  One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral Lesions 
The ideal treatment of osteochondral lesions is debatable. Although autologous chondrocyte implantation provides pain relief, the need for two operations and high costs has prompted a search for alternatives. Bone marrow-derived cells may represent the future in osteochondral repair. Using a device to concentrate bone marrow-derived cells and collagen powder or hyaluronic acid membrane as scaffolds for cell support and platelet gel, a one-step arthroscopic technique was developed for cartilage repair. We performed an in vitro preclinical study to verify the capability of bone marrow-derived cells to differentiate into chondrogenic and osteogenic lineages and to be supported onto scaffolds. In a prospective clinical study, we investigated the ability of this technique to repair talar osteochondral lesions in 48 patients. Minimum followup was 24 months (mean, 29 months; range, 24–35 months). Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score and the influence of scaffold type, lesion area, previous surgeries, and lesion depth was considered. MRI and histologic evaluation were performed. The AOFAS score improved from 64.4 ± 14.5 to 91.4 ± 7.7. Histologic evaluation showed regenerated tissue in various degrees of remodeling although none showed entirely hyaline cartilage. These data suggest the one-step technique is an alternative for cartilage repair, permitting improved functional scores and overcoming the drawbacks of previous techniques.
Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0885-8
PMCID: PMC2772930  PMID: 19449082
12.  Management of Focal Chondral Lesion in the Knee Joint 
Knee Surgery & Related Research  2011;23(4):185-196.
Articular cartilage does not contain vascular, nervous and lymphatic tissue and chondrocytes hardly participate in the healing or repair process of chondral tissue because of being surrounded by plenty of extracellular matrix. Therefore, the injury to articular cartilage frequently requires an operative treatment. The goal of surgical repair of articular cartilage is to regenerate nearly normal chondral tissue and prevent degenerative arthritis caused by the articular cartilage defect. Microfracture is a kind of cartilage repair procedure that makes a fibrin clot containing mesenchymal stem cells in the chondral lesion. Microfracture is a simple procedure but it has a disadvantage that the repaired tissue is fibrocartilage. Autologous chondrocyte implantation has an advantage that it implants fully differentiated chondrocytes to the lesion, which theoretically produces hyaline cartilage. Its disadvantages are that it is a two stage and a costly procedure. Osteochondral autograft transplantation is a one stage procedure and repairs the lesion with hyaline cartilage. But its limitation is the lack of donor site availability. Surgeons who understand the theoretical background, indications, surgical methods, rehabilitation, complications, and clinical course of cartilage repair procedures can achieve the goal of preventing degenerative arthritis.
doi:10.5792/ksrr.2011.23.4.185
PMCID: PMC3341803  PMID: 22570833
Knee joint; Articular cartilage; Focal chondral lesion; Management
13.  Surgical Treatment Options for Osteochondritis Dissecans of the Knee 
Sports Health  2009;1(4):326-334.
Osteochondritis dissecans of the knee is identified with increasing frequency in the young adult patient. Left untreated, osteochondritis dissecans can lead to the development of osteoarthritis at an early age, resulting in progressive pain and disability. Treatment of osteochondritis dissecans may include nonoperative or operative intervention. Surgical treatment is indicated mainly by lesion stability, physeal closure, and clinical symptoms. Reestablishing the joint surface, maximizing the osteochondral biologic environment, achieving rigid fixation, and ensuring early motion are paramount to fragment preservation. In cases where the fragment is not amenable to preservation, the treatment may include complex reconstruction procedures, such as marrow stimulation, osteochondral autograft, fresh osteochondral allograft, and autologous chondrocyte implantation. Treatment goals include pain relief, restoration of function, and the prevention of secondary osteoarthritis.
doi:10.1177/1941738109334216
PMCID: PMC3445128  PMID: 23015890
osteochondritis dissecans; knee; cartilage; surgical treatment
14.  MR imaging of osteochondral grafts and autologous chondrocyte implantation 
European Radiology  2006;17(1):103-118.
Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.
doi:10.1007/s00330-006-0333-z
PMCID: PMC1766022  PMID: 16802126
MRI; Articular cartilage; Cartilage repair; Autologous osteochondral transplantation; Autologous chondrocyte implantation
15.  The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction 
International Orthopaedics  2005;30(1):48-53.
We report our experience of using autologous chondrocyte implantation (ACI) to treat osteochondral defects of the knee in combination with anterior cruciate ligament (ACL) reconstruction. The outcome of symptomatic osteochondral lesions treated with ACI following previous successful ACL reconstruction is also reviewed. Patients were followed for a mean of 23 months. Nine patients underwent ACL reconstruction in combination with ACI. Mean modified Cincinnati knee scores improved from 42 to 69 following surgery. Seven patients described their knee as better and two as the same. A second group of nine patients underwent ACI for symptomatic articular cartilage defects following previous ACL reconstruction. In this group, the mean modified Cincinnati knee score improved from 53 to 62 after surgery. Six patients described their knee as better and three as worse. Combined treatment using ACI with ACL reconstruction is technically feasible and resulted in sustained improvement in pain and function. The results following previous ACL reconstruction also resulted in clinical improvement, although results were not as good as following the combined procedure.
doi:10.1007/s00264-005-0025-3
PMCID: PMC2254665  PMID: 16320051
16.  Radiographic Predictability of Cartilage Damage in Medial Ankle Osteoarthritis 
Background
Radiographic grading has been used to assess and select between treatment options for ankle osteoarthritis. To use radiographic grading systems in clinical practice and scientific studies one must have reliable systems that predict the fate of the cartilage.
Questions/purposes
We therefore asked whether (1) radiographic grading of ankle osteoarthritis is reliable and (2) grading reflects cartilage damage observed during arthroscopy. We then (3) determined the sensitivity, specificity, and predictive values of the radiographic findings.
Patients and Methods
We examined 74 ankles with medial osteoarthritis and 24 with normal articular cartilage based on arthroscopy. Arthroscopic findings were graded according to the modified Outerbridge grades and all radiographs were graded using the modified Kellgren-Lawrence, Takakura et al., and van Dijk et al. grading systems. The reliability of each radiographic grading system was evaluated. We correlated the radiographic grades and severity of cartilage damage for each radiographic grading system. Sensitivity, specificity, and predictive values of spurs and joint space narrowing with or without talar tilting then were determined.
Results
The interobserver weighted kappa ranged from 0.58 to 0.89 and the intraobserver weighted kappa from 0.51 to 0.85. The correlation coefficients for the Kellgren-Lawrence, Takakura et al., and van Dijk et al. grades were 0.53, 0.42, and 0.42, respectively. Ankles with medial joint space narrowing (Stage 2 of Takakura et al. and van Dijk et al. grades) showed varying severity of cartilage damage. The positive predictive value of cartilage damage increased from 77% for medial joint space narrowing regardless of the presence of talar tilting to 98% for medial joint space narrowing with talar tilting.
Conclusions
Our observations suggest the inclusion of talar tilting in grading schemes enhances the assessment of cartilage damage.
Level of Evidence
Level II, diagnostic study. See the Guidelines for Authors for a complete description of level of evidence.
doi:10.1007/s11999-010-1352-2
PMCID: PMC2895860  PMID: 20393817
17.  Results of Chondrocyte Implantation with a Fibrin-Hyaluronan Matrix: A Preliminary Study  
Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores. The MRI followup showed good filling of the defect with tissue having the imaging appearance of cartilage in all patients. Apart from the transient effusion in three patients we observed no other adverse events during the followup.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0322-4
PMCID: PMC2584266  PMID: 18528742
18.  Integration of Tissue-engineered Cartilage With Host Cartilage: An In Vitro Model 
Background
We developed a tissue-engineered biphasic cartilage bone substitute construct which has been shown to integrate with host cartilage and differs from autologous osteochondral transfer in which integration with host cartilage does not occur.
Questions/purposes
(1) Develop a reproducible in vitro model to study the mechanisms regulating tissue-engineered cartilage integration with host cartilage, (2) compare the integrative properties of tissue-engineered cartilage with autologous cartilage and (3) determine if chondrocytes from the in-vitro formed cartilage migrate across the integration site.
Methods
A biphasic construct was placed into host bovine osteochondral explant and cultured for up to 8 weeks (n = 6 at each time point). Autologous osteochondral implants served as controls (n = 6 at each time point). Integration was evaluated histologically, ultrastructurally, biochemically and biomechanically. Chondrocytes used to form cartilage in vitro were labeled with carboxyfluorescein diacetate which allowed evaluation of cell migration into host cartilage.
Results
Histologic assessment demonstrated that tissue-engineered cartilage integrated over time, unlike autologous osteochondral implant controls. Biochemically there was an increase in collagen content of the tissue-engineered implant over time but was well below that for native cartilage. Integration strength increased between 4 and 8 weeks as determined by a pushout test. Fluorescent cells were detected in the host cartilage up to 1.5 mm from the interface demonstrating chondrocyte migration.
Conclusions
Tissue-engineered cartilage demonstrated improved integration over time in contrast to autologous osteochondral implants. Integration extent and strength increased with culture duration. There was chondrocyte migration from tissue-engineered cartilage to host cartilage.
Clinical Relevance
This in vitro integration model will allow study of the mechanism(s) regulating cartilage integration. Understanding this process will facilitate enhancement of cartilage repair strategies for the treatment of chondral injuries.
doi:10.1007/s11999-011-1856-4
PMCID: PMC3171526  PMID: 21403985
19.  Matrix-induced autologous chondrocyte implantation for a large chondral defect in a professional football player: a case report 
Introduction
Matrix-assisted autologous chondrocyte implantation is a well-known procedure for the treatment of cartilage defects, which aims to establish a regenerative milieu and restore hyaline cartilage. However, much less is known about third-generation autologous chondrocyte implantation application in high-level athletes. We report on the two-year follow-up outcome after matrix-assisted autologous chondrocyte implantation to treat a large cartilage lesion of the lateral femoral condyle in a male Caucasian professional football player.
Case presentation
A 27-year-old male Caucasian professional football player was previously treated for cartilage problems of his left knee with two failed microfracture procedures resulting in a 9 cm2 Outerbridge Grade 4 chondral lesion at his lateral femoral condyle. Preoperative Tegner-Lysholm and Brittberg-Peterson scores were 64 and 58, and by the second year they were 91 and 6. An evaluation with magnetic resonance imaging demonstrated filling of the defect with the signal intensity of the repair tissue resembling healthy cartilage. Second-look arthroscopy revealed robust, smooth cartilage covering his lateral femoral condyle. He returned to his former competitive level without restrictions or complaints one year after the procedure.
Conclusions
This case illustrates that robust cartilage tissue can be obtained with a matrix-assisted autologous chondrocyte implantation procedure even after two failed microfracture procedures in a large (9 cm2) cartilage defect. To the best of our knowledge, this is the first case report on the application of the third-generation cell therapy treatment technique, matrix-assisted autologous chondrocyte implantation, in a professional football player.
doi:10.1186/1752-1947-6-173
PMCID: PMC3404975  PMID: 22742735
20.  Total Ankle Replacement Compatible with Ligament Function Produces Mobility, Good Clinical Scores, and Low Complication Rates: An Early Clinical Assessment 
Background
A three-part ankle replacement was developed to achieve compatibility with the natural ligaments by allowing fibers on the medial and lateral sides to remain isometric during passive motion. Unlike all current prostheses, the new design uses nonanatomically shaped components on the tibia and talus and a fully conforming interposed meniscal bearing.
Questions/purposes
Does this new design restore ankle mobility, improve clinical score, and result in low complication and early revision rates?
Patients and Methods
We reviewed 51 patients in whom 51 prostheses were implanted in a seven-center trial from July 2003 to July 2006. The mean age of the patients at surgery was 61.5 years (range, 35.1–82.5 years). We used the AOFAS score to assess clinical outcome. We used lateral radiographs to assess function. The minimum followup was 24 months (mean, 30 months; range, 24–48 months).
Results
The mean preoperative AOFAS score of 38.5 increased to 76.9, 79.1, 76.4, and 79.0 at 12, 24, 36, and 48 months, respectively. We observed a correlation between meniscal bearing movement on the tibial component (mean, 3.4 mm; range, 2–12 mm) and range of flexion at the replaced ankle (mean, 27.4º; range, 16º–53º). We revised one arthroplasty in the second postoperative year for lateral impingement, providing a 3-year cumulative survival rate of 97% and performed one other secondary operation for hindfoot pain.
Conclusions
These data suggest the new prosthesis can provide short-term restoration of ankle mobility, a good clinical score, and low complication and failure rates. Longer followup with larger numbers is required.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1432-3
PMCID: PMC3049631  PMID: 20559763
21.  Autologous chondrocyte implantation (ACI) for the treatment of large and complex cartilage lesions of the knee 
Background
Complex cartilage lesions of the knee including large cartilage defects, kissing lesions, and osteoarthritis (OA) represent a common problem in orthopaedic surgery and a challenging task for the orthopaedic surgeon. As there is only limited data, we performed a prospective clinical study to investigate the benefit of autologous chondrocyte implantation (ACI) for this demanding patient population.
Methods
Fifty-one patients displaying at least one of the criteria were included in the present retrospective study: (1.) defect size larger than 10 cm2; (2.) multiple lesions; (3.) kissing lesions, cartilage lesions Outerbridge grade III-IV, and/or (4.) mild/moderate osteoarthritis (OA). For outcome measurements, the International Cartilage Society's International Knee Documentation Committee's (IKDC) questionnaire, as well as the Cincinnati, Tegner, Lysholm and Noyes scores were used. Radiographic evaluation for OA was done using the Kellgren score.
Results and Discussion
Patient's age was 36 years (13-61), defects size 7.25 (3-17.5) cm2, previous surgical procedures 1.94 (0-8), and follow-up 30 (12-63) months. Instruments for outcome measurement indicated significant improvement in activity, working ability, and sports. Mean ICRS grade improved from 3.8 preoperatively to grade 3 postoperatively, Tegner grade 1.4 enhanced to grade 3.39. The Cincinnati score enhanced from 25.65 to 66.33, the Lysholm score from 33.26 to 64.68, the Larson score from 43.59 to 79.31, and Noyes score from 12.5 to 46.67, representing an improvement from Cincinnati grade 3.65 to grade 2.1. Lysholm grade 4 improved to grade 3.33, and Larson grade 3.96 to 2.78 (Table 1), (p < 0.001). Patients with kissing cartilage lesions had similar results as patients with single cartilage lesions.
Mean scores and grades at surgery (Tx) and at follow-up
Conclusion
Our results suggest that ACI provides mid-term results in patients with complex cartilage lesions of the knee. If long term results will confirm our findings, ACI may be a considered as a valuable tool for the treatment of complex cartilage lesions of the knee.
doi:10.1186/1758-2555-3-11
PMCID: PMC3114778  PMID: 21599992
22.  Trapezoidal osteochondral autologous plug single-block graft for treating chondral lesions of the knee: clinical and functional medium-term results in an observational study 
Clinics  2012;67(10):1191-1195.
OBJECTIVE:
To evaluate the clinical and functional results of autologous trapezoidal plug single-block grafts fixed with absorbable chondral darts in patients with osteochondral knee lesions of varying sizes.
METHODS:
Twenty-five patients underwent surgery from February 2000 to June 2008. Seventy-two percent of the patients were male, and the mean age was 29 years.
RESULTS:
The right side (56%) and the medial condyle (92%) were most affected. The lesions had an average area of 5.28 cm2, and the mean follow-up was 59 months. All of the variables other than instability showed significant improvements (p<0.05), as shown by the increase in the mean Lysholm score from 55 points preoperatively to 92 points (p<0.001) postoperatively. There was no loosening or collapse of the osteochondral graft. All of the patients had patellofemoral crepitation and pain for an average of six months.
CONCLUSION:
Autologous trapezoidal plug single-block grafts are a therapeutic option for defects of varying sizes and provide good clinical results and low morbidity at the donor site in the medium term.
doi:10.6061/clinics/2012(10)11
PMCID: PMC3460022  PMID: 23070346
Cartilage Diseases; Bone Transplantation; Knee; Subchondral Arthroplasty; Lesions
23.  Direction of the oblique medial malleolar osteotomy for exposure of the talus 
Introduction
A medial malleolar osteotomy is often indicated for operative exposure of posteromedial osteochondral defects and fractures of the talus. To obtain a congruent joint surface after refixation, the oblique osteotomy should be directed perpendicularly to the articular surface of the tibia at the intersection between the tibial plafond and medial malleolus. The purpose of this study was to determine this perpendicular direction in relation to the longitudinal tibial axis for use during surgery.
Materials and methods
Using anteroposterior mortise radiographs and coronal computed tomography (CT) scans of 46 ankles (45 patients) with an osteochondral lesion of the talus, two observers independently measured the intersection angle between the tibial plafond and medial malleolus. The bisector of this angle indicated the osteotomy perpendicular to the tibial articular surface. This osteotomy was measured relative to the longitudinal tibial axis on radiographs. Intraclass correlation coefficients (ICC) were calculated to assess reliability.
Results
The mean osteotomy was 57.2 ± 3.2° relative to the tibial plafond on radiographs and 56.5 ± 2.8 on CT scans. This osteotomy corresponded to 30.4 ± 3.7° relative to the longitudinal tibial axis. The intraobserver (ICC, 0.90–0.93) and interobserver (ICC, 0.65–0.91) reliability of these measurements were good to excellent.
Conclusion
A medial malleolar osteotomy directed at a mean 30° relative to the tibial axis enters the joint perpendicularly to the tibial cartilage, and will likely result in a congruent joint surface after reduction.
doi:10.1007/s00402-010-1227-8
PMCID: PMC3117279  PMID: 21165631
Medial malleolus; Osteotomy; Ankle; Radiography; Preoperative planning; Surgical approach
24.  Etiology of Ankle Osteoarthritis 
The purpose of this study was to evaluate the distribution rate of etiologies leading to ankle arthritis and to quantify and compare the important clinical and radiologic variables among these etiologic groups. We evaluated data from 390 patients (406 ankles) who consulted our center because of painful end-stage ankle osteoarthritis (OA) by using medical history, physical examination, and radiography. Posttraumatic ankle OA was seen in 78% of the cases (n = 318), secondary arthritis in 13% (n = 52), and primary OA in 9% (n = 36). The average American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was 38 points (range, 0–74 points), range of motion was 22° (range, 0°−65°), and visual analog scale for pain was 6.8 (range, 2–10). Patients with posttraumatic end-stage ankle OA were younger than patients with primary OA. The average tibiotalar alignment was 88° (range, 51°–116°) and did not differ between the etiologic groups. Our study showed trauma is the main cause of ankle OA and primary OA is rare. In the majority of patients with ankle OA the average tibiotalar alignment is varus regardless of the underlying etiology.
Level of Evidence: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0543-6
PMCID: PMC2690733  PMID: 18830791
25.  Midterm results of biologic fixation or mosaicplasty and drilling in osteochondritis dissecans 
Indian Journal of Orthopaedics  2011;45(5):445-449.
Background:
Osteochondritis dissecans (OCD) primarily affects subchondral bone. Multiple drilling, fixation implant or autogenous osteochondral grafts are reported as treatment options. We present the midterm results of cases in which an OCD lesion was treated by osteochondral autograft transfer and drilling.
Materials and Methods:
Between 2002 and 2006, 14 knees with International Cartilage Repair Society (ICRS-OCD) type II and III lesions were treated in our clinic using osteochondral autograft transfer and drilling by arthroscopic or open surgery. The average age of our patients was 22.14 years (range 17-29 years) and average followup was of 24.3 months (range 11-40 months). Lesion type was ICRS type II in five patients (35.7%) and ICRS type III in nine patients (64.3%). In cases with ICRS-OCD type II lesions, in situ fixation was applied following circumferential multiple drilling, while mosaicplasty was done following debridement and multiple drilling in cases with ICRS-OCD type III lesion. Mosaicplasty was performed in the lesion area by an average of 2.5 (range 1-3) cylindrical osteochondral autografts. Patients were not allowed to perform loading activities for 3 weeks in the postoperative period; movement was initiated by using CPM device in the early phase; full range of motion was achieved in third week, and full weight bearing was permitted in 6 to 8 weeks
Results:
While 6 and 8 patients were classified preoperatively as fair and poor, respectively, according to Hughston scale, excellent and good results were obtained postoperatively in 10 and 4 patients, respectively. During the followup, no problems were detected in any of the patients in the regions where osteochondral graft was harvested.
Conclusion:
Biologic fixation or mosaicplasty and drilling as a technique to treatment of the lesion in OCD by osteochondral autograft transfer has resulted in good and excellent clinical outcomes in our patients and it is considered that providing blood flow to subchondral bone by circumferencial drilling leads to an increase in the robustness of biological internal fixation and shortens the duration of recovery.
doi:10.4103/0019-5413.83137
PMCID: PMC3162682  PMID: 21886927
Osteochondritis dissecans; Hughston scale; knee; mosaicplasty

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