| 1. |
- Becher, Christoph, et al.
(författare)
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High degree of consensus amongst an expert panel regarding focal resurfacing of chondral and osteochondral lesions of the femur with mini-implants
- 2023
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Nature. - 0942-2056 .- 1433-7347. ; 31:9, s. 4027-4034
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The rationale for the use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions is still under debate. The evidence supporting best practise guidelines is based on studies with low-level evidence. A consensus group of experts was convened to collaboratively advance towards consensus opinions regarding the best available evidence. The purpose of this article is to report the resulting consensus statements. Methods: Twenty-five experts participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted via an online survey of two rounds, for initial agreement and comments on the proposed statements. An in-person meeting between the panellists was organised during the 2022 ESSKA congress to further discuss and debate each of the statements. A final agreement was made via a final online survey a few days later. The strength of consensus was characterised as: consensus, 51–74% agreement; strong consensus, 75–99% agreement; unanimous, 100% agreement. Results: Statements were developed in the fields of patient assessment and indications, surgical considerations and postoperative care. Between the 25 statements that were discussed by this working group, 18 achieved unanimous, whilst 7 strong consensus. Conclusion: The consensus statements, derived from experts in the field, represent guidelines to assist clinicians in decision-making for the appropriate use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions. Level of evidence: Level V.
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| 2. |
- Bodin, Aase Katarina, 1977, et al.
(författare)
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Bacterial cellulose as a potential meniscus implant
- 2007
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 1:5, s. 406-8
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic or degenerative meniscal lesions are a frequent problem. The meniscus cannot regenerate after resection. These lesions often progress and lead to osteoarthritis. Collagen meniscal implants have been used in clinical practice to regenerate meniscal tissue after partial meniscectomy. The mechanical properties of bacterial cellulose (BC) gel were compared with a collagen material and the pig meniscus. BC was grown statically in corn steep liquid medium, as described elsewhere. Pig meniscus was harvested from pigs. The collagen implant was packed in sterile conditions until use. The different materials were evaluated under tensile and compression load, using an Instron 5542 with a 500 N load cell. The feasibility for implantation was explored using a pig model. The Young's modulus of bacterial cellulose was measured to be 1 MPa, 100 times less for the collagen material, 0.01 MPa in tensile load. The Young's modulus of bacterial cellulose and meniscus are similar in magnitude under a compression load of 2 kPa and with five times better mechanical properties than the collagen material. At higher compression strain, however, the pig meniscus is clearly stronger. These differences are clearly due to a more ordered and arranged structure of the collagen fibrils in the meniscus. The combination of the facts that BC is inexpensive, can be produced in a meniscus shape, and promotes cell migration makes it an attractive material for consideration as a meniscus implant. Copyright (c) 2007 John Wiley & Sons, Ltd.
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| 3. |
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| 4. |
- Brittberg, Mats, 1953, et al.
(författare)
-
Autolog broskcellstransplantation. Smärtlindring och återställd ledfunktion är målet : Autologous cartilage cell transplantation. The goal is pain relief and restored joint function
- 1995
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Ingår i: Nordisk medicin. - 0029-1420. ; 110:12, s. 330-4
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Tidskriftsartikel (refereegranskat)abstract
- Chondral and osteochondral damage is a common result of trauma to the joints. The capacity of cartilage to heal such damage is poor, and repetitive wear on joint surfaces that do not heal results in impaired joint function, which can culminate in full blown arthrosis. Thus, it is important to improve our knowledge of cartilage regenerative potential, and develop methods to forestall progression to arthrosis by promoting the early healing of cartilage damage. Autologous cartilage cell transplantation may be a mean of healing cartilage damage. A method of cultivating autologous chondrocytes for transplantation in the treatment of isolated damage to articular cartilage of the knee is presented in the article.
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| 5. |
- Brittberg, Mats, 1953
(författare)
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Autologous chondrocyte implantation--technique and long-term follow-up
- 2008
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Ingår i: Injury. - : Elsevier BV. - 0020-1383. ; 39:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage has a limited capacity for self repair after injury. This biological deficiency has led to a variety of surgical attempts to improve the repair of injured articular cartilage surfaces over the past 50 years. The first example of clinical cartilage tissue engineering was performed in 1987 when a knee with an articular cartilage defect on the femoral condyle was treated by implanting the patient's own chondrocytes that had been expanded in vitro into the defect in combination with a covering mechanical membrane-the periosteum. This technology is either termed autologous chondrocyte transplantation (ACT) or autologous chondrocyte implantation (ACI). Today, many modifications of the technique exist, from the first generation to now second and third generations of chondrocyte implantation. This paper describes the basic techniques for the clinical use of chondrocyte implantation and gives an update on the clinical results.
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| 6. |
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| 7. |
- Brittberg, Mats, 1953, et al.
(författare)
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Autologous chondrocytes used for articular cartilage repair: an update.
- 2001
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :391 Suppl
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Forskningsöversikt (refereegranskat)abstract
- Articular cartilage in adults has a poor ability to self-repair after a substantial injury; however, it is not known whether there is a cartilage resurfacing technique superior to the existing techniques. It is not satisfactory that at the beginning of the new millennium, there still is a lack of randomized studies comparing different cartilage repair techniques and there still is little knowledge of the natural course of a cartilaginous lesion. To date, various articular cartilage resurfacing techniques have the potential to improve the repair of cartilage defects and reduce the patient's disability. One such cartilage repair technique is autologous chondrocyte transplantation combined with a periosteal graft. Since the first patient was operated on in 1987, much interest in cartilage repair and cell engineering has emerged. The experience with autologous chondrocyte transplantation during the past 13 years with in vitro chondrocyte expansion, cartilage harvest, and postoperative biopsy technique is discussed, and the latest followup of 213 consecutive patients in different subgroups with 2 to 10 years followup is presented. The technique gives stable long-term results with a high percentage of good to excellent results (84%-90%) in patients with different types of single femoral condyle lesions, whereas patients with other types of lesions have a lower degree of success (mean, 74%).
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| 8. |
- Brittberg, Mats, 1953, et al.
(författare)
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Cartilage repair in the degenerative ageing knee.
- 2016
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 87:supl. 363, s. 26-38
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation - Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints.
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| 9. |
- Brittberg, Mats, 1953
(författare)
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Cell carriers as the next generation of cell therapy for cartilage repair: a review of the matrix-induced autologous chondrocyte implantation procedure
- 2010
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Ingår i: The American Journal of Sports Medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 38:6, s. 1259-1271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the first patient was implanted with autologous cultured chondrocytes more than 20 years ago, new variations of cell therapies for cartilage repair have appeared. Autologous chondrocyte implantation, a first-generation cell therapy, uses suspended autologous cultured chondrocytes in combination with a periosteal patch. Collagen-covered autologous cultured chondrocyte implantation, a second-generation cell therapy, uses suspended cultured chondrocytes with a collagen type I/III membrane. Today's demand for transarthroscopic procedures has resulted in the development of third-generation cell therapies that deliver autologous cultured chondrocytes using cell carriers or cell-seeded scaffolds. PURPOSE: To review the current evidence of the matrix-induced autologous chondrocyte implantation procedure, the most widely used carrier system to date. Also discussed are the characteristics of type I/III collagen membranes, behavior of cells associated with the membrane, surgical technique, rehabilitation, clinical outcomes, and quality of repair tissue. STUDY DESIGN: Systematic review. METHODS: Relevant publications were identified by searching Medline from its inception (1949) to December 2007; peer-reviewed publications of preclinical and clinical cell behavior, manufacturing process, surgical technique, and rehabilitation protocols were identified. Preclinical and clinical studies were included if they contained primary data and used a type I/III collagen membrane. RESULTS: Data from these studies demonstrate that patients treated with matrix-induced autologous chondrocyte implantation have an overall improvement in clinical outcomes. Reduced visual analog scale pain levels (range, 1.7-5.32 points) and improvements in the modified Cincinnati (range, 3.8-34.2 points), Lysholm-Gillquist (range, 23.09-47.6 points), Tegner-Lysholm (range, 1.39-3.9 points), and International Knee Documentation Classification scale (P <.05) were observed. Patients had good-quality (hyaline-like) repair tissue as assessed by arthroscopic evaluation (including International Cartilage Repair Society score), magnetic resonance imaging, and histology, as well as a low incidence of postoperative complications. CONCLUSION: The findings suggest that matrix-induced autologous chondrocyte implantation is a promising third-generation cell therapy for the repair of symptomatic, full-thickness articular cartilage defects.
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| 10. |
- Brittberg, Mats, 1953
(författare)
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Cellular and Acellular Approaches for Cartilage Repair: A Philosophical Analysis
- 2015
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- There are several choices of cells to use for cartilage repair. Cells are used as internal or external sources and sometimes in combination. In this article, an analysis of the different cell choices and their use and potential is provided. Embryonic cartilage formation is of importance when finding more about how to be able to perfect cartilage repair. Some suggestions for near future research based on up-to-date knowledge on chondrogenic cells are given to hopefully stimulate more studies on the final goal of cartilage regeneration.
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| 11. |
- Brittberg, Mats, 1953, et al.
(författare)
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Cellular aspects on treatment of cartilage injuries.
- 1993
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Ingår i: Agents and actions. Supplements. - 0379-0363. ; 39, s. 237-41
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Tidskriftsartikel (refereegranskat)abstract
- Cellular aspects on articular cartilage growth and development are discussed. Cells with chondrogenic potential are described and current treatment models for cartilage injuries are considered. A rabbit model for treatment of articular cartilage defects with autologous cultured and transplanted chondrocytes for treatment of knee cartilage defects in humans are discussed.
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| 12. |
- Brittberg, Mats, 1953
(författare)
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Clinical articular cartilage repair-an up to date review
- 2018
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Ingår i: Annals of Joint. - : AME Publishing Company. - 2415-6809. ; 3:11
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Forskningsöversikt (refereegranskat)abstract
- Articular cartilage is a tissue with very limited self-renewal capacity due to its avascularity and lack of innervation. Many people develop severe disability after chondral and osteochondral traumatic injuries and there exist several options to treat such injuries in order to reduce pain and restore joint homeostasis. A disturbed joint homeostasis after joint trauma may induce generalized loss of cartilage with a risk of progression into a full organ disease: osteoarthritis. Repair long-term durability seems to be an important factor when to choose the right type of treatment. In this review, current non-operative and surgical treatments are presented and their possible place in the treatment toolbox is discussed.
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| 13. |
- Brittberg, Mats, 1953, et al.
(författare)
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Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.
- 2005
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584. ; 13:2, s. 146-53
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.
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| 14. |
- Brittberg, Mats, 1953
(författare)
-
Emerging technologies in cartilage repair
- 2018
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Ingår i: Cartilage restoration. Jack Farr, Andreas H. Gomoll (red.). - Cham : Springer. - 9783319771526 ; , s. 389-400
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Brittberg, Mats, 1953
(författare)
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Knee chondral delaminations and blisters
- 2022
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Ingår i: Journal of Cartilage and Joint Preservation. - : Elsevier BV. - 2667-2545. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage injuries are well known to be troublesome and difficult to treat. Such injuries are partial and full thickness lesions most often easily detectable on MRI scanning. However, less well-known are lesions that start between the calcified bone (in the calcified zone) and the bone plate and they are called chondral delaminations. Such lesions often take time to detect. If not found and treated they may develop into full thickness lesions. In a short review, the diagnosis and treatment alternatives are discussed.
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| 16. |
- Brittberg, Mats, 1953
(författare)
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Knee osteochondritis dissecans-treatment technical aspects
- 2022
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Ingår i: Journal of Orthopaedics. - : Elsevier BV. - 0972-978X. ; 34, s. 104-110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose and objective: Current treatments of different stages of knee osteochondritis Dissecans (OCD) are depending on the age of the patients and the stability of the diseased osteochondral area. The purpose of this paper was to summarize the treatment alternatives in order to simplify the choice for the treating surgeon. Background and principle results: Osteochondritis dissecans (OCD) of the knee is an idiopathic and local osteochondral abnormality that affects mainly children and adolescents with risk of loosening of osteochondral fragments. A good clinical result can be expected when the physes are still open, when the osteochondritis is small and when the osteochondritis can be assessed as stable by MRI. Unstable OCD lesions most often need to be treated operatively by different fixation methods and when the osteochondral cannot be refixated, different local chondral and osteochondral repairs are available to fill up the defect area to congruity Summary and major conclusions: The final choice of which treatment to use is depending on fragment viability and forms. Viable fragments are refixated while poor quality fragments are removed followed by a local biological osteochondral repair. Such osteochondral resurfacing may be single bone marrow stimulation with or without scaffold augmentation or different cell seeded grafts.
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| 17. |
- Brittberg, Mats, 1953, et al.
(författare)
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Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Five-Year Follow-up of a Prospective Randomized Trial
- 2018
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 46:6, s. 1343-1351
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix-based cell therapy improves surgical handling, increases patient comfort, and allows for expanded indications with better reliability within the knee joint. Five-year efficacy and safety of autologous cultured chondrocytes on porcine collagen membrane (MACI) versus microfracture for treating cartilage defects have not yet been reported from any randomized controlled clinical trial. Purpose: To examine the clinical efficacy and safety results at 5 years after treatment with MACI and compare these with the efficacy and safety of microfracture treatment for symptomatic cartilage defects of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This article describes the 5-year follow-up of the SUMMIT (Superiority of MACI Implant Versus Microfracture Treatment) clinical trial conducted at 14 study sites in Europe. All 144 patients who participated in SUMMIT were eligible to enroll; analyses of the 5-year data were performed with data from patients who signed informed consent and continued in the Extension study. Results: Of the 144 patients randomized in the SUMMIT trial, 128 signed informed consent and continued observation in the Extension study: 65 MACI (90.3%) and 63 microfracture (87.5%). The improvements in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain and Function domains previously described were maintained over the 5-year follow-up. Five years after treatment, the improvement in MACI over microfracture in the co-primary endpoint of KOOS pain and function was maintained and was clinically and statistically significant (P =.022). Improvements in activities of daily living remained statistically significantly better (P =.007) in MACI patients, with quality of life and other symptoms remaining numerically higher in MACI patients but losing statistical significance relative to the results of the SUMMIT 2-year analysis. Magnetic resonance imaging (MRI) evaluation of structural repair was performed in 120 patients at year 5. As in the 2-year SUMMIT (MACI00206) results, the MRI evaluation showed improvement in defect filling for both treatments; however, no statistically significant differences were noted between treatment groups. Conclusion: Symptomatic cartilage knee defects 3 cm2 or larger treated with MACI were clinically and statistically significantly improved at 5 years compared with microfracture treatment. No remarkable adverse events or safety issues were noted in this heterogeneous patient population. © 2018, © 2018 The Author(s).
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| 18. |
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| 19. |
- Brittberg, Mats, 1953
(författare)
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New frontiers for cartilage repair, joint preservation and prevention
- 2022
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Ingår i: Journal of Cartilage and Joint Preservation. - : Elsevier BV. - 2667-2545. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Damaged cartilage is seen with increasing frequency after joint trauma, alone or in combination with other joint injuries. A poor healing of injured cartilage leads to great disability and pain and could by time develop into osteoarthritis (OA). During the last 50 years, new cartilage repair techniques have appeared with more or less satisfactory results. In this presentation, the focus is to present areas that we might see more of in the future. It is important to separate local cartilage repair from a generalized loss of cartilage as OA. For both conditions, a base is a non-operative treatment with focus on new techniques of physiotherapy. Intra-articular injections of stem cells are mainly for OA as a source of growth factors but also as an adjunct to improve repair quality when using intrinsic local repairs. The use of in vitro manipulated chondrogeneic cells has decreased during the last decade due to strict regulations and high production costs. Instead, the focus is now on 1 stage procedures with autologous chondrogeneic cells but also more use of allogeneic chondrogeneic cells either alone or combined with autologous cells. An area of interest is the 3D technology used for bio printing of the lesions. Concomitant injuries are taken care as part of joint preservation and we need to better use preventive means to avoid future injuries. The assembled knowledge of joint repair, preservation and joint damage prevention may help us to reach the goal of going from local repair to a local regeneration become feasible.
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| 20. |
- Brittberg, Mats, 1953, et al.
(författare)
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Rabbit articular cartilage defects treated with autologous cultured chondrocytes.
- 1996
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :326, s. 270-83
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Tidskriftsartikel (refereegranskat)abstract
- Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to the found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.
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| 21. |
- Brittberg, Mats, 1953
(författare)
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The articular joint and its intriguing gliding surfaces.
- 2014
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 22:6, s. 1205-1206
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Brittberg, Mats, 1953, et al.
(författare)
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Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
- 1994
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Ingår i: The New England journal of medicine. - 0028-4793. ; 331:14, s. 889-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. METHODS. The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. RESULTS. Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage. CONCLUSION. Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
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| 23. |
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| 24. |
- Concaro, Sebastian, et al.
(författare)
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Effect of cell seeding concentration on the quality of tissue engineered constructs loaded with adult human articular chondrocytes.
- 2008
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 2:1, s. 14-21
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Tidskriftsartikel (refereegranskat)abstract
- Many aspects of the process of in vitro differentiation of chondrocytes in three-dimensional (3D) scaffolds need to be further investigated. Chitosan scaffolds were produced by freeze-drying 3% w/v 90% DDA chitosan gels. The effect of the cell seeding concentration was evaluated by culturing human adult chondrocytes in chitosan scaffolds After the first passage, cells were seeded into chitosan scaffolds with a diameter of 8 mm. The final cell seeding concentration per cm3 of chitosan scaffold was: Group A, 3 x 10(6); Group B, 6 x 10(6); Group C, 12 x 10(6); and Group D, 25 x 10(6) cells. After 14 and 28 days in 3D culture, the constructs were assesed for collagen, glucosaminoglycans and DNA content. The mechanical properties of the constructs were determined using a dynamic oscillatory shear test. The histological aspect of the constructs was evaluated using the Bern score. The collagen and GAG concentration increased, varying the cell seeding concentration. There was a significant increase in proteoglycan and hydroxyproline production between groups C and D. The sulphated GAG content increased significantly in the group D as compared to the other groups. The mechanical properties of the different constructs increased over time, from 9.6 G'/kPa at 14 days of 3D culture to 14.6 G'/kPa at 28 days under the same culture conditions. In this study we were able to determine that concentrations of 12-25 million cells/cm2 are needed to increase the matrix production and mechanical properties of human adult chondrocytes under static conditions.
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| 25. |
- de Windt, Tommy S, et al.
(författare)
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Is Magnetic Resonance Imaging Reliable in Predicting Clinical Outcome After Articular Cartilage Repair of the Knee?: A Systematic Review and Meta-analysis.
- 2013
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 41:7, s. 1695-1702
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:While MRI can provide a detailed morphological evaluation after articular cartilage repair, its additional value in determining clinical outcome has yet to be determined. PURPOSE:To evaluate the correlation between MRI and clinical outcome after cartilage repair and to identify parameters that are most important in determining clinical outcome. STUDY DESIGN:Systematic review and meta-analysis. METHODS:A systematic search was performed in Embase, MEDLINE, and the Cochrane Collaboration. Articles were screened for relevance and appraised for quality. Guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement were used. Chi-square tests were performed to find variables that could determine correlation between clinical and radiological parameters. RESULTS:A total of 32 articles (total number of patients, 1019) were included. A majority (81%) were case series or cohort studies that used similar standardized MRI techniques. The mean Coleman score was 63 (range, 42-96). For the majority of MRI parameters, limited or no correlation was found. Nine studies (28%) found a correlation between clinical outcome and the composite magnetic resonance observation of cartilage repair tissue (MOCART) or Henderson score and 7 (22%) with defect fill. In 5 studies, a weak to moderate correlation was found between clinical outcome and the T2 index (mean Pearson coefficient r = .53). CONCLUSION:Strong evidence to determine whether morphological MRI is reliable in predicting clinical outcome after cartilage repair is lacking. Future research aiming specifically at clinical sensitivity of advanced morphological and biochemical MRI techniques after articular cartilage repair could be of great importance to the field.
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| 26. |
- de Windt, Tommy S, et al.
(författare)
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Strategies for patient profiling in articular cartilage repair of the knee: a prospective cohort of patients treated by one experienced cartilage surgeon.
- 2012
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 20:11, s. 2225-32
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to report on the clinical outcome of a large heterogenic cartilage repair population treated with the profiling strategies of one experienced cartilage surgeon to provide evidence based tools for treatment selection in a clinical environment. METHODS: A total of 216 patients were identified in this prospective single-surgeon study. For the primary and secondary treatment of smaller defects, microfracture (MF) was used. Hyalograft C was used for first and second line larger defects, while carbon-fiber rod and pad implantations were used as a salvage procedure. RESULTS: Three years after the initial procedure, the clinical improvement was excellent for MF and Hyalograft C (P<0.001) and good for carbon-fiber procedures (P<0.05). Hyalograft C patients with prior anterior cruciate ligament reconstruction had less clinical improvement (P<0.05), while MF patients with prior cartilage repair were more likely to fail (Odds Ratio 20.5, P<0.05). CONCLUSION: This is the first study that provides an assessment of the treatment strategies used by an experienced cartilage surgeon. A treatment algorithm for cartilage repair in a heterogenic population was created that based on the findings of this study could be implemented in a clinical environment. LEVEL OF EVIDENCE: Prospective clinical case series, Level IV.
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| 27. |
- de Windt, T. S., et al.
(författare)
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Treatment and Prevention of (Early) Osteoarthritis Using Articular Cartilage Repair-Fact or Fiction? A Systematic Review
- 2013
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 4:3 SUPPL.
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Tidskriftsartikel (refereegranskat)abstract
- Early osteoarthritis (OA) is increasingly being recognized in patients who wish to remain active while not accepting the limitations of conservative treatment or joint replacement. The aim of this systematic review was to evaluate the existing evidence for treatment of patients with early OA using articular cartilage repair techniques. A systematic search was performed in EMBASE, MEDLINE, and the Cochrane collaboration. Articles were screened for relevance and appraised for quality. Nine articles of generally low methodological quality (mean Coleman score 58) including a total of 502 patients (mean age range = 36-57 years) could be included. In the reports, both radiological and clinical criteria for early OA were applied. Of all patients included in this review, 75% were treated with autologous chondrocyte implantation. Good short-term clinical outcome up to 9 years was shown. Failure rates varied from 8% to 27.3%. The conversion to total knee arthroplasty rate was 2.5% to 6.5%. Although a (randomized controlled) trial in this patient category with long-term follow-up is needed, the literature suggests autologous chondrocyte implantation could provide good short- to mid-term clinical outcome and delay the need for total knee arthroplasty. The use of standardized criteria for early OA and implementation of (randomized) trials with long-term follow-up may allow for further expansion of the research field in articular cartilage repair to the challenging population with (early) OA. © The Author(s) 2013.
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| 28. |
- Enochson, Lars, et al.
(författare)
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GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition.
- 2014
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1522-9653. ; 22:4, s. 566-77
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Tidskriftsartikel (refereegranskat)abstract
- Growth differentiation factor 5 (GDF5) is important for joint formation and associated with osteoarthritis (OA). Its role for the homeostasis of cartilage extracellular matrix (ECM) is, however, unknown. The canonical Wnt signaling pathway is also implemented in OA and activation of the pathway has detrimental effects on the cartilage ECM. The objective of this study was to investigate the effect of GDF5 stimulation on the Wnt signaling pathway and on the expression of known modulators of cartilage ECM.
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| 29. |
- Enochson, Lars, et al.
(författare)
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Optimization of a chondrogenic medium through the use of factorial design of experiments.
- 2012
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Ingår i: BioResearch open access. - : Mary Ann Liebert Inc. - 2164-7844 .- 2164-7860. ; 1:6, s. 306-13
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Tidskriftsartikel (refereegranskat)abstract
- The standard culture system for in vitro cartilage research is based on cells in a three-dimensional micromass culture and a defined medium containing the chondrogenic key growth factor, transforming growth factor (TGF)-β1. The aim of this study was to optimize the medium for chondrocyte micromass culture. Human chondrocytes were cultured in different media formulations, designed with a factorial design of experiments (DoE) approach and based on the standard medium for redifferentiation. The significant factors for the redifferentiation of the chondrocytes were determined and optimized in a two-step process through the use of response surface methodology. TGF-β1, dexamethasone, and glucose were significant factors for differentiating the chondrocytes. Compared to the standard medium, TGF-β1 was increased 30%, dexamethasone reduced 50%, and glucose increased 22%. The potency of the optimized medium was validated in a comparative study against the standard medium. The optimized medium resulted in micromass cultures with increased expression of genes important for the articular chondrocyte phenotype and in cultures with increased glycosaminoglycan/DNA content. Optimizing the standard medium with the efficient DoE method, a new medium that gave better redifferentiation for articular chondrocytes was determined.
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| 30. |
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| 31. |
- Foldager, C. B., et al.
(författare)
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Aarhus Regenerative Orthopaedics Symposium (AROS): Regeneration in the ageing population
- 2016
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 87, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- The combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem.
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| 32. |
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| 33. |
- Gatenholm, Birgitta, 1986, et al.
(författare)
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Collagen 2A Type B Induction after 3D Bioprinting Chondrocytes In Situ into Osteoarthritic Chondral Tibial Lesion.
- 2021
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6043 .- 1947-6035. ; 13:2 (Suppl.)
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Tidskriftsartikel (refereegranskat)abstract
- Large cartilage defects and osteoarthritis (OA) cause cartilage loss and remain a therapeutic challenge. Three-dimensional (3D) bioprinting with autologous cells using a computer-aided design (CAD) model generated from 3D imaging has the potential to reconstruct patient-specific features that match an articular joint lesion.To scan a human OA tibial plateau with a cartilage defect, retrieved after total knee arthroplasty, following clinical imaging techniques were used: (1) computed tomography (CT), (2) magnetic resonance imaging (MRI), and (3) a 3D scanner. From such a scan, a CAD file was obtained to generate G-code to control 3D bioprinting in situ directly into the tibial plateau lesion.Highest resolution was obtained using the 3D scanner (2.77 times more points/mm2 than CT), and of the 3 devices tested, only the 3D scanner was able to detect the actual OA defect area. Human chondrocytes included in 3D bioprinted constructs produced extracellular matrix and formed cartilage tissue fragments after 2 weeks of differentiation and high levels of a mature splice version of collagen type II (Col IIA type B), characteristic of native articular cartilage and aggrecan (ACAN). Chondrocytes had a mean viability of 81% in prints after day 5 of differentiation toward cartilage and similar viability was detected in control 3D pellet differentiation of chondrocytes (mean viability 72%).Articular cartilage can be formed in 3D bioprints. Thus, this 3D bioprinting system with chondrocytes simulating a patient-specific 3D model provides an attractive strategy for future treatments of cartilage defects or early OA.
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| 34. |
- Gatenholm, Birgitta, 1986, et al.
(författare)
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Neuropeptides: important regulators of joint homeostasis
- 2019
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:3, s. 942-949
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA). Purpose: This review explores the mechanisms of joint pain with a special focus on the role of neuropeptides in pain transmission and their potential role in the progression of joint degeneration as seen in osteoarthritis. Methods: A literature search was performed on papers published between January 1990 and September 2017 using the Web of Science Core Collection, MEDLINE and Scopus databases. Results: What is seen in the subchondral bone and synovia is mirrored in the central nervous system (CNS). Substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y are the major peptides involved both in the generation of pain as well as reducing pain post-joint trauma. The interplay between them and other neuropeptides and cytokines influence how noxious stimuli are transduced, transmitted and modulated for a final pain perception as part of a complex cascade of events. There is a close interaction between the different components in the joint that together cross-talk to adapt to load and catabolic factors during injury and inflammation. Conclusion: The articular joint should be seen as an organ where local joint pain development and maintenance is influenced by interplay between the local transmitters in the joints as well as their dependence on the CNS. A slow-release cocktail of mixed antibodies targeted against neuropeptides and receptor blockers/stimulators involved in the events of early joint pain or any inflammatory joint disease is a future treatment target. Level of evidence: V.
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| 35. |
- Gatenholm, Birgitta, 1986, et al.
(författare)
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Peptidomic analysis of cartilage and subchondral bone in OA patients
- 2019
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 49:5
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Stichting European Society for Clinical Investigation Journal Foundation Background: The objective of this study was to develop a method for directly analysing osteochondral samples straight out of the operating room without cell culturing, thereby enabling identification of potential peptide biomarkers to better understand the mechanisms involved in the development of osteoarthritis and pain. Material and Methods: Osteochondral plugs from wounded and macroscopically nonwounded zones of the femur condyle were collected from six patients with manifest osteoarthritis (OA) undergoing total knee arthroplasty (TKA). The samples were demineralized and supernatant was collected and isotopically marked with Tandem Mass Tag (TMT) labelling and analysed using liquid chromatography coupled with tandem mass spectrometry LC-MS/MS. Results: Using peptidomics, 6292 endogenous peptides were identified. Five hundred sixty-six peptides (8 identified endogenous peptides) differed significantly (P-value 0.10) from wounded zones compared to nonwounded zones. Conclusion: This pilot study shows promising results for enabling peptidomic analysis of cartilage and bone straight out of the operating room. With further refinement, peptidomics can potentially become a diagnostic tool for OA, and improve the knowledge of disease progression and genesis of pain.
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| 36. |
- Gatenholm, Birgitta, 1986, et al.
(författare)
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Spatially matching morphometric assessment of cartilage and subchondral bone in osteoarthritic human knee joint with micro-computed tomography
- 2019
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 120, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Objective: The objective of this study was to develop a reproducible and semi-automatic method based on micro computed tomography (microCT) to analyze cartilage and bone morphology of human osteoarthritic knee joints in spatially matching regions of interest. Materials and methods: Tibial plateaus from randomly selected patients with advanced osteoarthritis (OA) who underwent total knee arthroplasty surgery were microCT scanned once fresh and once after staining with Hexabrix. The articular surface was determined manually in the first scan. Total articular surface, defect surface and cartilage surface were computed by triangulation of the cartilage surface and the spatially corresponding subchondral bone regions were automatically generated and the standard cortical bone and trabecular bone morphometric indices were computed. Results: The method to identify cartilage surface and defects was successfully validated against photographic examinations. The microCT measurements of the cartilage defect were also verified by conventional histopathology using safranin O–stained sections. Cartilage thickness and volume was significantly lower for OA condyle compared with healthy condyle. Bone fraction, bone tissue mineral density, cortical density and trabecular thickness differed significantly depending on the level of cartilage damage. Conclusion: This new microCT imaging workflow can be used for reproducible quantitative evaluation of articular cartilage damage and the associated changes in subchondral bone morphology in osteoarthritic joints with a relatively high throughput compared to manual contouring. This methodology can be applied to gain better understanding of the OA disease progress in large cohorts.
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| 37. |
- Goyal, Deepak, et al.
(författare)
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Consideration of religious sentiments while selecting a biological product for knee arthroscopy.
- 2013
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 21:7, s. 1577-1586
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: There is an increasing use of various synthetic and biological products in orthopaedics. The use of a biological product can be a major area of concern for patients of various cultures/religions. The purpose of this work is to study various restrictions in different faiths and their compatibility with available products focused on cartilage repair. METHODS: A systematic search in several databases, CINAHL, EMBASE, Global health, PubMed, MEDLINE and the Cochrane collaboration, was performed to find out various religious beliefs of some major religions regarding the use of animal products. Hindu, Muslim, Christian, Jewish and Buddhist faiths were studied to find out whether animal-derived surgical implants are permitted. Major religious scholars were asked about their opinions, and guidelines related to human/religious ethics were evaluated. A market survey was carried out to find out biological contents of various products and their compatibility. RESULTS: Jews and Muslims have religious restrictions for porcine products, while Hindus reject bovine products. Vegetarian Hindus reject usage of any animal product. Most Christians do not have any restrictions except those who follow vegetarian dietary regulations. Though there is no prohibition for the use of animal products in Buddhism, a code of non-violence to animals is being followed. However, difference of opinion exists about interpretation of these dietary guidelines for surgical usage amongst various scholars. CONCLUSION: Products of biological origin have a definite restriction for various religions, with few exceptions. Surgeons should know the source of the product and should be aware of the basic requirements of the patient's faith. Patient should be informed about the source of the product and alternative if available, and an informed consent may be considered. LEVEL OF EVIDENCE: Type of study, Level V.
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| 38. |
- Holz, J., et al.
(författare)
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Patient-specific metal implants for focal chondral and osteochondral lesions in the knee; excellent clinical results at 2years
- 2021
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 29, s. 2899-2910
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Surgical treatment options for the management of focal chondral and osteochondral lesions in the knee include biological solutions and focal metal implants. A treatment gap exists for patients with lesions not suitable for arthroplasty or biologic repair or who have failed prior cartilage repair surgery. This study reports on the early clinical and functional outcomes in patients undergoing treatment with an individualised mini-metal implant for an isolated focal chondral defect in the knee. Methods: Open-label, multicentre, non-randomised, non-comparative retrospective observational analysis of prospectively collected clinical data in a consecutive series of 80 patients undergoing knee reconstruction with the Episealer® implant. Knee injury and Osteoarthritis Outcome Score (KOOS) and VAS scores, were recorded preoperatively and at 3months, 1year, and 2years postoperatively. Results: Seventy-five patients were evaluated at a minimum 24months following implantation. Two patients had undergone revision (2.5%), 1 declined participation, and 2 had not completed the full data requirements, leaving 75 of the 80 with complete data for analysis. All 5 KOOS domain mean scores were significantly improved at 1 and 2years (p < 0.001–0.002). Mean preoperative aggregated KOOS4 of 35 (95% CI 33.5–37.5) improved to 57 (95% CI 54.5–60.2) and 59 (95% CI 55.7–61.6) at 12 and 24months respectively (p < 0.05). Mean VAS score improved from 63 (95% CI 56.0–68.1) preoperatively to 32 (95% CI 24.4–38.3) at 24months. The improvement exceeded the minimal clinically important difference (MCID) and this improvement was maintained over time. Location of defect and history of previous cartilage repair did not significantly affect the outcome (p > 0.05). Conclusion: The study suggests that at 2years, Episealer® implants are safe with a low failure rate of 2.5% and result in clinically significant improvement. Individualised mini-metal implants with appropriate accurate guides for implantation appear to have a place in the management of focal femoral chondral and osteochondral defects in the knee. Level of evidence: IV. © 2020, The Author(s).
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| 39. |
- Jungmann, P. M., et al.
(författare)
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Magnetic Resonance Imaging Score and Classification System (AMADEUS) for Assessment of Preoperative Cartilage Defect Severity
- 2017
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 8:3, s. 272-282
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To design a simple magnetic resonance (MR)–based assessment system for quantification of osteochondral defect severity prior to cartilage repair surgery at the knee. Design: The new scoring tool was supposed to include 3 different parameters: (1) cartilage defect size, (2) depth/morphology of the cartilage defect, and (3) subchondral bone quality, resulting in a specific 3-digit code. A clearly defined numeric score was developed, resulting in a final score of 0 to 100. Defect severity grades I through IV were defined. For intra- and interobserver agreement, defects were assessed by 2 independent readers on preoperative knee MR images of n = 44 subjects who subsequently received cartilage repair surgery. For statistical analyses, mean values ± standard deviation (SD), interclass correlation coefficients (ICC), and linear weighted kappa values were calculated. Results: The mean total Area Measurement And DEpth & Underlying Structures (AMADEUS) score was 48 ± 24, (range, 0-85). The mean defect size was 2.8 ± 2.6 cm2. There were 36 of 44 full-thickness defects. The subchondral bone showed defects in 21 of 44 cases. Kappa values for intraobserver reliability ranged between 0.82 and 0.94. Kappa values for interobserver reliability ranged between 0.38 and 0.85. Kappa values for AMADEUS grade were 0.75 and 0.67 for intra- and interobserver agreement, respectively. ICC scores for the AMADEUS total score were 0.97 and 0.96 for intra- and interobserver agreement, respectively. Conclusions: The AMADEUS score and classification system allows reliable severity encoding, scoring and grading of osteochondral defects on knee MR images, which is easily clinically applicable in daily practice. © 2016, © The Author(s) 2016.
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| 40. |
- Karlsson, Camilla, 1977, et al.
(författare)
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Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis.
- 2010
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1522-9653. ; 18:4, s. 581-92
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Tidskriftsartikel (refereegranskat)abstract
- Although the extracellular matrix (ECM) is the functional element in articular cartilage and its degradation is central in the pathogenetic process in osteoarthritis (OA), increasing the knowledge about the cellular OA phenotype is essential. The aim of this study is therefore to provide a more complete picture of the cellular and molecular alterations detected in OA cartilage.
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| 41. |
- Kon, E., et al.
(författare)
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A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:9, s. 2704-2715
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. Methods In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. Results A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. Conclusions This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions.
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| 42. |
- Lindahl, Anders, 1954, et al.
(författare)
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Cartilage and Bone Regeneration
- 2014
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Ingår i: Tissue Engineering: Second Edition. - Amsterdam : Elsevier, Inc.. ; , s. 529-582
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Bokkapitel (refereegranskat)abstract
- This chapter deals with the tissue engineering aspects of one of the mesenchymal tissues-cartilage. It includes a brief description of the different cartilage types and their embryonal origin. Tissue structures including chondrocyte and extracellular matrix components are described in detail. The disease aspect of hyaline cartilage with emphasis on cartilage injuries and the tissue engineering approach to cartilage regeneration with the autologous chondrocyte implantation technique is described in depth. The future aspects of cartilage regeneration techniques with potential cell types other than autologous chondrocytes as well as new promising scaffold techniques are described. © 2015 Elsevier Inc. All rights reserved.
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| 43. |
- Lindahl, Anders, 1954, et al.
(författare)
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Cartilage repair with chondrocytes: clinical and cellular aspects.
- 2003
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Ingår i: Novartis Foundation symposium. - 1528-2511. ; 249
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Forskningsöversikt (refereegranskat)abstract
- Articular cartilage has a limited potential to repair. Unsatisfactory results with current treatment methods (e.g. osteochondral autografts, drilling or microfracturing) has triggered the development of new cartilage restoration techniques including autologous cell transplantation (mesenchymal stem cells or chondrocytes) with or without supporting scaffolds. Autologous chondrocyte transplantation (ACT) was first used in humans in 1987 and the first pilot was published in 1994. Two years after transplantation, 14 of the 16 patients with femoral condyle transplants had a restored joint function and 11 of 15 femoral transplants demonstrated a hyaline repair tissue. Results from patellar transplants were less encouraging. To date, we have treated over 1000 and other groups over 6000 patients. The technique gives stable long-term results with a high percentage of good to excellent results (84-90%) in patients with different types of single femoral condyle lesions, whereas in patients with other types of lesions in the knee it is less successful (average 74%). A better understanding of the repair mechanism induced by the cultured chondrocytes and the regulatory mechanisms controlling chondrogenic differentiation combined with identification and culture of stem cells with chondrogenic potential will be the key to new cartilage treatments.
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| 44. |
- Lindahl, Anders, 1954, et al.
(författare)
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Health economics benefits following autologous chondrocyte transplantation for patients with focal chondral lesions of the knee.
- 2001
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 0942-2056. ; 9:6, s. 358-63
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Tidskriftsartikel (refereegranskat)abstract
- Autologous chondrocyte transplantation (ACT) for the treatment of cartilage injuries has been in clinical use for several years. Since this new technique is potentially more costly and invasive than traditional conservative therapies, we evaluated the effect of ACT on clinical outcome, absenteeism, disability status, and total direct economic burden in 57 patients with full-thickness chondral lesions of the knee treated between 1987 and 1996. Patients graded good or excellent following ACT in the treatments groups were: femoral condyles (28/33), femoral condyles with anterior cruciate ligament (ACL) repair (5/5), osteochondritis dissecans (7/8), and patellar lesions (9/11). Pre-ACT, 57/57 patients were disabled and post-ACT (mean follow-up 7.3 years) 44/57 had no sickness, 10/57 had minor disability, and 1/57 was disabled. Two of the 57 patients suffered re-injury during the follow-up time. In the 10-year period prior to ACT, the average cost of absenteeism and surgery was SEK 982,457 ($ 122,807) and SEK 47,000 ($ 5,875), respectively, compared to the post-ACT period where both absenteeism and medical costs were dramatically reduced: SEK 9,508 ($ 1,189) and SEK 7,050 ($ 881), respectively. In conclusion, 49 of the 57 patients improved clinically as a result of the ACT treatment. A dramatic cost-saving effect was demonstrated over a projected 10-year period due to reduced absenteeism and disability.
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| 45. |
- Mithoefer, Kai, et al.
(författare)
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Guidelines for the design and conduct of clinical studies in knee articular cartilage repair: International cartilage repair society recommendations based on current scientific evidence and standards of clinical care
- 2011
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 2, s. 100-121
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project. © The Author(s) 2011.
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| 46. |
- Nesic, Dobrila, et al.
(författare)
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Cartilage tissue engineering for degenerative joint disease.
- 2006
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Ingår i: Advanced drug delivery reviews. - : Elsevier BV. - 0169-409X. ; 58:2, s. 300-22
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Tidskriftsartikel (refereegranskat)abstract
- Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed.
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| 47. |
- Nguyen, Duong, 1986, et al.
(författare)
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Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage lesions can progress into secondary osteoarthritis and cause severe clinical problems in numerous patients. As a prospective treatment of such lesions, human-derived induced pluripotent stem cells (iPSCs) were shown to be 3D bioprinted into cartilage mimics using a nanofibrillated cellulose (NFC) composite bioink when co-printed with irradiated human chondrocytes. Two bioinks were investigated: NFC with alginate (NFC/A) or hyaluronic acid (NFC/HA). Low proliferation and phenotypic changes away from pluripotency were seen in the case of NFC/HA. However, in the case of the 3D-bioprinted NFC/A (60/40, dry weight % ratio) constructs, pluripotency was initially maintained, and after five weeks, hyaline-like cartilaginous tissue with collagen type II expression and lacking tumorigenic Oct4 expression was observed in 3D -bioprinted NFC/A (60/40, dry weight % relation) constructs. Moreover, a marked increase in cell number within the cartilaginous tissue was detected by 2-photon fluorescence microscopy, indicating the importance of high cell densities in the pursuit of achieving good survival after printing. We conclude that NFC/A bioink is suitable for bioprinting iPSCs to support cartilage production in co-cultures with irradiated chondrocytes.
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| 48. |
- Nimkingratana, Puwapong, 1982, et al.
(författare)
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Returning to Work After Articular Cartilage Repair Intervention: A Systematic Review
- 2020
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to significant benefits for the general population. Purpose: To determine which surgical interventions are most effective in helping patients return to work after cartilage repair and to identify factors that affect the ability to return to work. Study Design: Systematic review; Level of evidence, 4. Methods: This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in analyzing reports on articular cartilage treatment and return to work published from January 1966 (when the first system of classifying articular cartilage injuries based on the mechanism of injuries and type of lesions was developed) to January 2019. General surgical information and available clinical scores were used to assess outcomes. Results: Only 5 studies describing 283 patients were found to be relevant to our objectives and were therefore included in the analysis. Autologous chondrocyte implantation (ACI) and osteochondral allografts were the only 2 procedures for which information was included regarding patient return to work rates. The mean (overall) return-to-work time after a cartilage repair operation was 4.80 ± 3.02 months. ACI was the most common procedure (3 studies; 227 patients). Return to work after ACI or ACI with high tibial osteotomy (HTO) occurred in almost 100% of cases, whereas the rate of return to work was 51.78% for patients who underwent osteochondral allograft (P <.01); further, patients who had ACI or ACI+HTO returned to work sooner compared with patients who underwent osteochondral allograft. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE) scores were significantly higher in patients who fully returned to work. No significant difference was found in rates of return to work after ACI related to sex, area of the lesion, or size of the defect. Conclusion: The vast majority of published results on articular cartilage repair do not include data on return to work. Although available data on articular cartilage repair in the general population reveal a high rate of return to work, including those patients treated with ACI, the data do not stratify patients by the type and demand of work. No randomized studies have examined return-to-work rates. Hence, authors should include these data in future studies. A refined definition of work intensity, rather than just return to work, may provide a clearer picture of the relative effectiveness of different surgical interventions. To that end, the authors propose a return to work prognostic score called the Prognostic Cartilage Repair Return to Work Score, or PROCART-RTW score. © The Author(s) 2020.
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| 49. |
- Olivos-Meza, A., et al.
(författare)
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Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair
- 2023
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Ingår i: Cell and Tissue Banking. - : Springer Science and Business Media LLC. - 1389-9333 .- 1573-6814. ; 24:4, s. 725-735
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Tidskriftsartikel (refereegranskat)abstract
- Autologous chondrocyte implantation has shown optimal long-term outcomes in the treatment of cartilage lesions. The challenge for a single-stage approach lies in obtaining sufficient number of cells with high viability. The answer could lie in supplementing or replacing them with allogenic chondrocytes coming from cadaveric donors. In the present work, we aimed to compare the number of viable cells isolated from cartilage of live and cadaveric donors and to determine the suitable characteristics of the best donors. A total of 65 samples from donors aged from 17 to 55 years, either women or men, were enrolled in this study (33 living vs. 32 cadaveric). The mean time of hours from death to processing samples in cadaveric donors was higher compared to live donors (64.3 +/- 17.7 vs. 4.6 +/- 6.4). The number of isolated chondrocytes per gram of cartilage was higher in cadaveric donors (5.389 x 10(6) compared to 3.067 x 10(6) in living donors), whereas the average of cell viability was comparable in both groups (84.16% cadaveric, 87.8% alive). It is possible to obtain viable chondrocytes from cartilage harvested from cadaveric donors, reaching a similar cell number and viability to that obtained from the cartilage of living donors.
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| 50. |
- Peterson, Lars, 1936, et al.
(författare)
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Autologous Chondrocyte Implantation: A Long-term Follow-up.
- 2010
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 38:6, s. 1117-1124
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported. HYPOTHESIS: Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients' files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again. RESULTS: There were 224 of 341 patients who replied to our posted questionnaires and were assessed. The mean cartilage lesion size was 5.3 cm(2). Ten to 20 years after the implantation (mean, 12.8 years), 74% of the patients reported their status as better or the same as the previous years. There were 92% who were satisfied and would have the ACI again. The Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were improved compared with the preoperative values. The average Lysholm score improved from 60.3 preoperatively to 69.5 postoperatively, the Tegner from 7.2 to 8.2, and the Brittberg-Peterson from 59.4 to 40.9. At the final measurement, the KOOS score was on average 74.8 for pain, 63 for symptoms, 81 for activities of daily living (ADL), 41.5 for sports, and 49.3 for quality of life (QOL). The average Noyes score was 5.4. Patients with bipolar lesions had a worse final outcome than patients with multiple unipolar lesions. The presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not appear to affect the final outcomes. The age at the time of the operation or the size of lesion did not seem to correlate with the final outcome. CONCLUSION: Autologous chondrocyte implantation as emerged as an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee joint. Our study suggests that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.
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