Repair Of Articular Cartilage Lesions Research Articles

Morphological and Molecular Evaluation of the Tissue Repair following Nasal Septum Biopsy in a Sheep Model.

Nasal septal pathologies requiring surgical intervention are common in the population. Additionally, nasal chondrocytes are becoming an important cell source in cartilage tissue engineering strategies for the repair of articular cartilage lesions. These procedures damage the nasal septal cartilage whose healing potential is limited due to its avascular, aneural, and alymphatic nature. Despite the high incidence of various surgical interventions that affect septum cartilage, limited nasal cartilage repair characterizations have been performed to date. To evaluate the healing of the nasal septum cartilage perforation, a septal biopsy was performed in 14 sheep. Two and 6 months later, the tissue formed on the place of perforation was explanted and compared with the native tissue. Tissue morphology, protein and gene expression of explanted tissue was determined using histological, immunohistochemical and real-time quantitative polymerase chain reaction analysis. Tissue formed on the defect site, 2 and 6 months after the biopsy was characterized as mostly connective tissue with the presence of fibroblastic cells. This newly formed tissue contained no glycosaminoglycans and collagen type II but was positively stained for collagen type I. Cartilage-specific genes COL2, AGG, and COMP were significantly decreased in 2- and 6-month samples compared with the native nasal cartilage. Levels of COL1, COL4, and CRABP1 genes specific for perichondrium and connective tissue were higher in both test group samples in comparison with native cartilage. Newly formed tissue was not cartilage but rather fibrous tissue suggesting the role of perichondrium and mucosa in tissue repair after nasal septum injury.

Hyaluronic acid hydrogels reinforced with laser spun bioactive glass micro- and nanofibres doped with lithium

The repair of articular cartilage lesions in weight-bearing joints remains as a significant challenge due to the low regenerative capacity of this tissue. Hydrogels are candidates to repair lesions as they have similar properties to cartilage extracellular matrix but they are unable to meet the mechanical and biological requirements for a successful outcome. Here, we reinforce hyaluronic acid (HA) hydrogels with 13-93-lithium bioactive glass micro- and nanofibres produced by laser spinning. The glass fibres are a reinforcement filler and a platform for the delivery of therapeutic lithium-ions. The elastic modulus of the composites is more than three times higher than in HA hydrogels. Modelling of the reinforcement corroborates the experimental results. ATDC5 chondrogenic cells seeded on the composites are viable and more proliferation occurs on the hydrogels containing fibres than in HA hydrogels alone. Furthermore, the chondrogenic behavior on HA constructs with fibres containing lithium is more marked than in hydrogels with no-lithium fibres.

Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions

Background: Autologous chondrocyte implantation, which uses passaged chondrocytes, commonly leads to the formation of fibrocartilage. When chondrocytes are passaged to increase cell numbers, they lose their phenotype and ability to form hyaline cartilage. The use of transforming growth factor β (TGFβ) to redifferentiate passaged chondrocytes has been validated in vitro; however, it is unknown if redifferentiated chondrocytes will enhance defect repair when implanted in vivo. Furthermore, fibrin gel is used in orthopaedic surgery as a fixative and scaffold and could be an appropriate carrier to enhance retention of cells in the repair site. Purpose: To investigate if passaged redifferentiated chondrocytes in fibrin gel have the ability to form cartilage tissue and if these redifferentiated cells will enhance the formation of hyaline cartilage in vivo when implanted into critical-size osteochondral defects. Study Design: Controlled laboratory study. Methods: Rabbit and human chondrocytes were serially passaged twice in monolayer culture. Twice-passaged cells were used directly (dedifferentiated) or redifferentiated in high-density culture with TGFβ3. Dedifferentiated or redifferentiated cells were mixed with fibrin gel to form fibrin clots, which were cultured in vitro to assess the use of fibrin gel as a scaffold or implanted in vivo in a critical-size osteochondral defect in New Zealand White rabbit knee joints. Rabbits were sacrificed 6 weeks after implantation, and tissues were assessed histologically and by immunohistochemistry. Results: Redifferentiation of passaged chondrocytes by means of 3-dimensional culture in the presence of TGFβ3 improved the formation of cartilaginous tissues in vitro, and culture in fibrin gel did not affect the cell phenotype. Implantation of dedifferentiated cells in vivo resulted in fibrocartilaginous repair tissues. Redifferentiated chondrocyte implants resulted in granulation tissues containing the hyaline cartilage marker collagen type 2. Conclusion: Redifferentiated chondrocytes will maintain their chondrogenic differentiation in fibrin clots. Implanted redifferentiated chondrocytes show a different reparative response than dedifferentiated chondrocytes and do not appear to enhance repair at an early time point. Another study of longer duration is required to assess tissue maturation over time. Clinical Relevance: Redifferentiation of passaged chondrocytes with TGFβ3 before implantation does not improve defect repair in the first 6 weeks.

Redifferentiated Chondrocytes for the Repair of Articular Cartilage Lesions

Objectives:Biological therapies such as autologous chondrocyte implantation which use serially passaged chondrocytes to repair cartilage defects, are often unsuccessful as they lead to the formation of fibrocartilage. Fibrocartilage is rich in collagen type 1 (Col1) and lacks the structural complexity, low friction, and load distribution properties of articular cartilage. Fibrocartilage forms as a result of the phenotype of passaged chondrocytes. When serially passaged in monolayer to increase cell numbers, chondrocytes lose their phenotype in a process termed “dedifferentiation”. This is characterized by a loss in the production of collagen type II (Col2) and aggrecan (Acan), the major extracellular matrix molecules of articular cartilage, and an increase in the production of Col1. Therefore, to increase the success of therapies which use passaged chondrocytes, these cells must be redifferentiated to re-establish an articular cartilage phenotype prior to implantation in a cartilage lesion. Transforming growth factor beta (TGFβ) signalling is known to play important roles in both cell differentiation and articular cartilage repair. However, intra-articular injections with TGFβ have been shown to result in osteophyte formation and fibrosis of synovial tissues. Therefore, redifferentiating passaged chondrocytes in vitro using TGFβ prior to their use in vivo may be a better alternative. Fibrin glue is commonly used in orthopaedics to maintain cells in a cartilage lesion, however the effects of fibrin glue on chondrocytes have not been fully investigated. Thus we hypothesize that passaged chondrocytes redifferentiated in vitro with TGFβ will maintain their phenotype and form articular cartilage-like tissue when embedded in fibrin glue in the absence of further exogenous supplementation with TGFβ in vitro.Methods:Chondrocytes were enzymatically isolated from rabbit articular cartilage and serially passaged in monolayer twice (P2) to increase cell number and facilitate dedifferentiation. P2 cells were cultured in scaffold-free 3D using a chondrogenic serum-free media supplemented with 10ng/ml TGFβ3 to facilitate redifferentiation. Redifferentiated chondrocytes were then embedded in fibrin glue (Tisseel, Baxter) at 1.5 x 106 cells/20uL and cultured for 2 weeks in vitro in the absence of TGFβ3. Controls were P2 cells that were not redifferentiated with TGFB3 prior to embedding in fibrin glue. Histology and immunohistochemistry were used to assess tissue formation and cell phenotype.Results:Redifferentiated chondrocytes accumulated more matrix rich in Col2 and Acan than controls (Figure 1). Furthermore, redifferentiated chondrocytes had a round cell shape characteristic of articular chondrocytes. The use of fibrin glue did not impair the ability of redifferentiated chondrocytes to accumulate matrix nor did it affect cell phenotype.Conclusion:Redifferentiated chondrocytes in fibrin glue may be a better alternative to passaged chondrocytes for cell based articular cartilage repair therapies as they accumulate more Col2 and Acan containing matrix than undifferentiated P2. In vivo studies are required to elucidate the potential for redifferentiated chondrocytes in cartilage repair.

Effects of combined rAAV-mediated TGF-\u03b2 and sox9 gene transfer and overexpression on the metabolic and chondrogenic activities in human bone marrow aspirates

BackgroundTransplantation of genetically modified bone marrow concentrates is an attractive approach to conveniently activate the chondrogenic differentiation processes as a means to improve the intrinsic repair capacities of damaged articular cartilage.MethodsHuman bone marrow aspirates were co-transduced with recombinant adeno-associated virus (rAAV) vectors to overexpress the pleiotropic transformation growth factor beta (TGF-β) and the cartilage-specific transcription factor sox9 as a means to enhance the chondroreparative processes in conditions of specific lineage differentiation.ResultsSuccessful TGF-β/sox9 combined gene transfer and overexpression via rAAV was achieved in chondrogenically induced human bone marrow aspirates for up to 21 days, the longest time point evaluated, leading to increased proliferation, matrix synthesis, and chondrogenic differentiation relative to control treatments (reporter lacZ treatment, absence of vector application) especially when co-applying the candidate vectors at the highest vector doses tested. Optimal co-administration of TGF-β with sox9 also advantageously reduced hypertrophic differentiation in the aspirates.ConclusionsThese findings report the possibility of directly modifying bone marrow aspirates by combined therapeutic gene transfer as a potent and convenient future approach to improve the repair of articular cartilage lesions.

Chondrogenic Differentiation Processes in Human Bone Marrow Aspirates upon rAAV-Mediated Gene Transfer and Overexpression of the Insulin-Like Growth Factor I.

Direct therapeutic gene transfer in marrow concentrates is an attractive strategy to conveniently enhance the chondrogenic differentiation processes as a means to improve the healing response of damaged articular cartilage upon reimplantation in sites of injury. In the present study, we evaluated the ability of the clinically adapted recombinant adeno-associated virus (rAAV) vectors to mediate overexpression of the insulin-like growth factor I (IGF-I) in human bone marrow aspirates that may modulate the proliferative, anabolic activities, and chondrogenic differentiation potential in such samples in vitro. The results demonstrate that successful, significant rAAV-mediated IGF-I gene transfer and expression were achieved in transduced aspirates (up to 105.9±35.1 pg rhIGF-I/mg total proteins) over time (21 days) at very high levels (∼80% of cells expressing the candidate IGF-I transgene), leading to increased levels of proliferation, matrix synthesis, and chondrogenic differentiation over time compared with the control (lacZ) condition. Treatment with the candidate IGF-I vector also stimulated the hypertrophic and osteogenic differentiation processes in the aspirates, suggesting that the regulation of IGF-I expression through rAAV will be a prerequisite for future translation of the approach in vivo. However, these findings show the possible benefits of this vector class to directly modify marrow concentrates as a convenient tool for strategies that aim at improving the repair of articular cartilage lesions.

Are surface antigens suited to verify the redifferentiation potential and culture purity of human chondrocytes in cell-based implants.

Cell expansion in vitro is a prequisite to obtain a sufficient quantity of cells for cell-based cartilage repair of articular cartilage lesions. During this process verification of redifferentiation potential of highly expanded chondrocytes is required. Furthermore, cellular impurities of chondrocyte cultures have to be excluded. For this purpose, redifferentiation of expanded human chondrocytes in passage 3 or 5 was initiated in bioresorbable polyglycolic acid-fibrin (PGA-fibrin) scaffolds and selected potential markers were analysed during the process of cell expansion and redifferentiation. Chondrocyte expansion was accompanied by a decrease of collagen type II and COMP and an increase of collagen type I expression indicating cell dedifferentiation. Redifferentiation of chondrocytes in PGA-fibrin scaffolds was accompanied by an increase of collagen II/I ratio. Flow cytometric analyses revealed that in contrast to CD44 and CD49e, CD63 and CD166 showed significant changes in the number of positive cells during redifferentiation. CD14 and CD45 are not expressed by chondrocytes and are therefore possible candidates to detect specifically monocytes or haematopoetic cells in chondrocyte cultures. Characterization of surface antigen expression revealed two promising candidates (CD63 and CD166) to describe the process of redifferentiation, while CD14 and CD45 are suitable markers to exclude impurities by monocytes or haematopoetic cells.

An International Randomized Clinical Trial Evaluating Bst-Cargel®, A Novel Scaffold For Cartilage Repair, Demonstrates Superiority of Repair When Compared with Microfracture Alone Treatment

An international RCT with 80 patients evaluating BST-CarGel®, a novel chitosan-based scaffold applied to a cartilage lesion, showed superiority to microfracture alone for both the degree of lesion filling and the quality of cartilage repair tissue at 12 months by quantitative MRI and microscopic analyses of biopsies. Equivalent safety and clinical improvement at 12 months was also demonstrated. An international, multicenter randomized clinical trial was conducted to evaluate the efficacy and safety of BST-CarGel® (Piramal Healthcare, Laval, Canada), for the repair of articular cartilage lesions, compared to microfracture alone. BST-CarGel® is a device composed of the biomaterial chitosan (polyglucosamine) which is applied over a microfractured lesion. 80 patients at international sites (Canada, Spain, South Korea) were randomized (1:1) to either BST-CarGel®+microfracture or microfracture alone. Enrolled patients were aged 18 to 55, with BMIs=30 and had a single, symptomatic, grade III or IV lesion on their femoral condyles. They followed standardized 12-week post-operative rehabilitation. Quantity and quality of cartilage repair tissue was assessed at 12 months using quantitative MRI techniques. Supplemental structural data (ICRS I and II Histology Scoring and Polarized Light Microscopy (PLM) scoring) was also obtained from elective osteochondral biopsies taken at an average of 13 months from 38 consenting patients. Clinical improvement was measured at 12 months using WOMAC and SF-36 questionnaires, and safety was evaluated by monitoring adverse events. Blinded MRI analysis demonstrated that BST-CarGel® met both primary endpoints by achieving statistical superiority for BST-CarGel® in greater % Lesion Fill (p=0.0105) and more cartilage-like repair tissue T2 values (p=0.0330) when compared with microfracture alone. WOMAC assessments for pain, stiffness and function yielded equivalent improvement for both groups at 12 months, which were statistically significant (p<0.0001) from baseline. Safety was comparable for both groups. When compared to microfracture, BST-CarGel® repair tissue showed improved ICRS macroscopic grading (p=0.0002) at second-look arthroscopy, superior collagen organization by PLM (p=0.0003), and improvements in most histological parameters (4/6 ICRS-I and 10/14 ICRS-II, with 8 at (p<0.05) or near significance (p<0.11)). When compared to microfracture alone, the treatment of focal cartilage lesions with BST-CarGel® resulted in greater quantity and superior quality of cartilage repair tissue at 12 months as demonstrated by multiple, independent indicators.

Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells

Human serum has the potential for mesenchymal progenitor cell recruitment in repair of articular cartilage lesions. It is unclear which factor(s) in serum mediate this migratory effect. Our goal was to identify cell recruiting factors in human serum fractions obtained by ion exchange chromatography. The recruiting activity of serum fractions on human subchondral mesenchymal progenitor cells was analyzed using 96-well chemotaxis assays. Protein composition of recruiting serum fractions were analyzed by mass spectrometry and showed 58 potential candidates. Fibronectin, gelsolin, lumican, thrombospondin-1 and WNT-9a were identified as key candidates for progenitor cell recruitment. Only human plasma derived and recombinant fibronectin showed significant recruiting activity on progenitors reaching 50–90% of the recruiting activity of normal human serum. Presence of fibronectin in all human serum fractions with recruiting activity was verified by Western blot analysis. This study shows that fibronectin is a key factor in human serum to recruit mesenchymal progenitor cells and might be involved in subchondral mesenchymal progenitor cell migration into cartilage defects after microfracture.

Articular Cartilage-Derived Stem Cells: Identification, Characterisation and their Role in Spontaneous Repair

The poor reparative potential of articular cartilage is largely attributed to its avascular and aneural status combined with low cellularity; chondrocytes only occupy 10% of the tissue volume. Consequently, there have been a number of strategies developed to augment repair most notably through microfracture and Autologous Chondrocyte Implanation (ACI). However, both of these techniques have limitations. In the case of microfracture, the repair tissue is often fibrocartilaginous and in ACI, the number of cells that can be generated that maintain chondrogenicity is limited thus restricting the size of defect that can be treated. Consequently, there has been increasing interest in the use of Mesenchymal Stem Cells (MSCs) for the treatment of cartilage defects. Here, we discuss the isolation and characterization of a tissue-specific stem cell population from articular cartilage and the potential for its use in intrinsic and extrinsic repair of articular cartilage lesions. Significantly, unlike MSCs isolated from bone marrow, upon differentiation into the chondrogenic lineage, these cells fail to terminally differentiate i.e. are not endochondral, failing to synthesize both collagen type X and alkaline phosphatase. Senescence of chondrocytes following injury or as part of aging is hypothesized to be integral to degenerative disease and correlates with significant telomere erosion within chondrocytes. Articular cartilage-derived stem cells exhibit detectable telomerase activity and exhibit reduced erosion of telomeres; therefore, we hypothesize maintenance of this population is critical to tissue homeostasis.

Friction and wear behaviour of bacterial cellulose against articular cartilage

Bacterial cellulose (BC) is a natural and biocompatible material with unique properties, such as high water holding capacity, ultra-fine fibre network and high strength that makes it an attractive material for the repair of articular cartilage lesions. However, data on the tribological properties of BC is very scarce, particularly if natural articular cartilage is involved in the contact. In this work, unmodified BC pellicles were grown from Gluconacetobacter xylinus in order to be used as tribological samples against bovine articular cartilage (BAC) in the presence of phosphate buffered saline (PBS). The tribological assessment of the sliding pairs was accomplished using reciprocating pin-on-flat tests at 37 °C. The reciprocating sliding frequency and stroke length were kept constant at 1 Hz and 8 mm, respectively. Contact pressures ranging from 0.80 to 2.40 MPa were applied. The friction coefficient evolution was continuously monitored during the tests and the release of total carbohydrates into the lubricating solution was followed by means of the phenol–H2SO4 method as an attempt to evaluate wear losses. The morphology of worn surfaces was characterized by SEM/EDS and the main wear mechanisms were identified. Low friction coefficient values (∼0.05) combined with the preservation of the mating surfaces (BC and BAC) indicate the potential of BC to be used as artificial cartilage for articular joints.

Etanercept Enhances Preservation of Osteochondral Allograft Viability

Background: Osteochondral allografts are an increasingly popular treatment for the repair of articular cartilage lesions. Current tissue bank protocols require bacteriological testing that takes from 21 to 28 days to process. During this time, tumor necrosis factor–alpha (TNF-α, a proapoptotic cytokine) is upregulated, resulting in loss of chondrocyte viability. To date, etanercept (a cytokine inhibitor) has not been studied in the current storage paradigm with the intention of preserving cell viability. Purpose: This study was undertaken to assess whether the addition of etanercept can improve the chondrocyte viability ofosteochondral allograft during storage. Study Design: Controlled laboratory study. Methods: Osteochondral allografts were harvested from 8 Boer goat femurs and placed into storage media and stored at 4°C for 28 days. The experimental group was supplemented with 10 µg/mL of etanercept. After storage, cell viability was assessed by live/dead staining and confocal microscopy. Specimens were also analyzed histologically and underwent histomorphologic analysis. TNF-α expression was measured with semiquantitative polymerase chain reaction. Results: At 28 days, the percentage viability of the superficial zone in etanercept-treated allografts was maintained at significantly higher levels than those measured in the untreated group (69.3 ± 9.4 compared with 47.8 ± 19.1, P = .01). No difference was found histologically between the etanercept and the untreated group (ie, safranin O staining for glycosaminoglycan expression). Histomorphologic assessment showed no difference in indentation stiffness or roughness between groups. TNF-α expression was significantly decreased in the etanercept group compared to the untreated group. Conclusion: Etanercept was able to maintain cell viability of osteochondral allografts significantly better than the current storage paradigm after 28 days of storage. Clinical Relevance: Maintaining the viability of the superficial zone will benefit outcomes by facilitating joint articulation via improved lubrication. Additionally, maintaining the cellular viability for increased periods of time may allow a greater window of time in which a suitable recipient may be found.

Treatment Selection in Articular Cartilage Lesions of the Knee

Background Several treatment options are available to repair articular cartilage lesions of the knee; however, evidence-based parameters for treatment selection are lacking. Purpose To identify parameters for valid treatment selection in the repair of articular cartilage lesions of the knee. Study Design Systematic review. Methods A systematic search was conducted in the databases EMBASE, MEDLINE, and the Cochrane collaboration. The retrieved articles were screened for relevance on title and abstract followed by a full-text study quality appraisal of the remaining articles. Eventually, a total of 4 randomized controlled trials were included. Results Lesion size, activity level, and age were the influencing parameters for the outcome of articular cartilage repair surgery. Lesions greater than 2.5 cm2 should be treated with sophisticated techniques, such as autologous chondrocyte implantation or osteochondral autologous transplantation, while microfracture is a good first-line treatment option for smaller (<2.5 cm2) lesions. Patients who are active show better results after autologous chondrocyte implantation or osteochondral autologous transplantation when compared with microfracture. Younger patients (<30 years) seem to benefit more from any form of cartilage repair surgery compared with those over 30 years of age. Conclusion Lesion size, activity level, and patient age are factors that should be considered in selecting treatment of articular cartilage lesions of the knee. In addition, these factors are a step toward evidence-based, instead of surgeon-preferred, treatment of articular cartilage lesions of the knee.

Ultrastructure of hybrid chitosan–glycerol phosphate blood clots by environmental scanning electron microscopy

Chitosan-based polymers have been extensively studied for biomedical applications. Recently, liquid solutions of chitosan in a glycerol phosphate buffer (chitosan-GP) with physiological pH and osmolality were mixed with autologous blood to form hybrid chitosan-GP/blood implants that improved the repair of articular cartilage lesions in a large animal model. The mixture of chitosan-GP and blood forms a viscous liquid, which solidifies in minutes via normal blood coagulation as well as chitosan-mediated mechanisms. Here we have examined the ultrastructure of these chitosan-GP/blood clots as well as regular blood clots and chitosan-GP gels, the latter produced by heating. Both unfixed and fixed samples of chitosan-GP/blood clots, regular blood clots, and chitosan-GP gels were investigated by environmental scanning electron microscopy (ESEM) in conjunction with energy dispersive X-ray spectrometry (EDS), the former permitting direct observation of the ultrastructure in hydrated conditions simulating the natural state. By examination of unfixed specimens using ESEM we found that chitosan formed a network structure in both chitosan-GP gels and chitosan-GP/blood clots; however this structure was altered by aldehyde fixation to produce artifactual aggregates of chitosan microparticles. We were also able to identify chitosan in chitosan-GP/blood clots by washing samples in low concentration NaCl solutions followed by local EDS analyses to identify excess chloride versus sodium, and thus presence of cationic chitosan in analyzed features. Additional results indicated that the majority of glycerol phosphate diffuses freely from chitosan-GP gels (by EDS of phosphorus) and that hyperosmotic paraformaldehyde-based fixatives (i.e. 4% w/v) significantly disturb erythrocyte morphology in fixed whole blood clots.

Enhancing tissue integration in cartilage repair procedures

Arguably, the gold standard of biological repair of articular cartilage lesions is autologous chondrocyte transplantation. Although the clinical outcomes appear to range between good and excellent in most cases, there are, nevertheless, both clinical and biological challenges that remain to improve rehabilitation and clinical outcome. One of the major biological problems relates to tissue integration of the reparative tissue into the host tissue at a predictable level. Often within a single lesion, varying degrees of integration can be observed from total integration through to non-integration as one passes through the defect. Here we briefly review some of the literature relating to this problem and include some of our own data drawn from questions we have posed about the biological nature of cartilage/cartilage integration. The nature and status of the tissue that comprises the wound lesion edge is central to tissue integration, and controlling aspects of trauma and free-radical-induced cell death together with matrix synthesis are identified as two components that require further investigation. Interestingly, there appears to be a limited ability of chondrocytes to be able to infiltrate existing cartilage matrices and even to occupy empty chondrocyte lacunae. Proliferation as a result of blunt and sharp trauma shows differential responses. As expected, blunt trauma induces a greater proliferative burst than sharp trauma and is more widespread from the lesion edge. However, in the case of sharp trauma, the basal cells enter proliferation before surface zone chondrocytes, which is not the case in blunt wounds. Regulation of these and associated processes will be necessary in order to devise strategies that can predict successful integration in biological repair procedures.

Chondral Resurfacing of Articular Cartilage Defects in the Knee with the Microfracture Technique

BACKGROUND: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. METHODS: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m2. Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.

Chondral Resurfacing of Articular Cartilage Defects in the Knee with the Microfracture Technique

Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m(2). Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.

Repair of articular cartilage lesions in aged chickens by allogeneic transplantation of fresh embryonic epiphyses

The potential of fresh whole chick epiphyses of embryonic origin to serve as implant material for cartilage defects of aged chicken was tested. Fresh epiphyses of 11-day-old embryos were collected from 24 animals and transplanted into defects created in the weight-bearing areas of tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were examined macroscopically and microsections were prepared for histology. Macroscopically, control defects remained empty at all the time intervals. Defects of the experimental group were, on the other hand, filled with cartilaginous tissue as early as 2 weeks posttransplantation, although individual epiphyses could still be noted in the implant tissue. At 4 weeks and later, defects were filled with cartilaginous material indistinguishable from hyaline cartilage. Histologically, all grafts remained within the defect's pits, showing mitotic and metabolic activity typical to proliferating hyaline cartilage. The engrafted epiphyses showed a partial incorporation and integration with the surrounding host tissues already at 2 weeks. At 4 weeks and later, the integration was complete. It is concluded that a chick embryonic epiphyseal cartilage is suitable as a graft source for articular cartilage transplantation. The embryonic epiphyses provide immediate inherent stability to the graft and supply a good mix of mesenchymal progenitor cells responsible for the high rate of cell proliferation and adhesion to the differentiated committed chondrocytes of the host that create the typical favorable chondrogenic milieu. Based on the present findings, it is postulated that human embryonic epiphyses may, in the future, represent an alternative source to the commonly used techniques of hyaline cartilage repair.

Cartilage repair on magnesium scaffolds used as a subchondral bone replacement

AbstractDespite the availability of surgical and non‐surgical techniques, the repair of articular cartilage lesions remains a current clinical problem. Especially for the treatment of large osteochondral cartilage defects, the replacement of the subchondral bone plate is a crucial step for optimal cartilage repair. However, no artificial implant material can yet fully restore the properties of the subchondral bone plate. For optimal cartilage tissue repair, mechanical stability for the first two months is essential. Subsequently, a rapid degradation process of the implant material would allow optimal supply of nutrition to the regenerating tissue. To this end, we investigated whether the implantation of an open porous degradable scaffold made of a magnesium alloy (AZ91) could serve as a sufficient temporary replacement of the subchondral bone plate. The results show that this alloy degrades too rapid in vivo to allow sufficient cartilage repair above the scaffold. However, the surrounding cartilage tissue was not negatively affected by the rapid degradation process and new bone formation was observed at the rim of the degrading implant. In conclusion, magnesium scaffolds degrade in vivo but the initial high corrosion rate must be reduced to allow the formation of an appropriate cartilage tissue. Future research will therefore be directed to optimized alloys and additional coating with magnesium fluorides or calcium phosphates like hydroxyapatite.

THE MICROFRACTURE TECHNIQUE FOR THE TREATMENT OF ARTICULAR CARTILAGE LESIONS IN THE KNEE

Background: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. Methods: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. Results: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m2. Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. Conclusions: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.