Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo

Purpose

The combination of chondrogenic factors might be necessary to adequately stimulate articular cartilage repair. In previous studies, enhanced repair was observed following transplantation of chondrocytes overexpressing human insulin-like growth factor I (IGF-I) or fibroblast growth factor 2 (FGF-2). Here, the hypothesis that co-overexpression of IGF-I and FGF-2 by transplanted articular chondrocytes enhances the early repair of cartilage defects in vivo and protects the neighbouring cartilage from degeneration was tested.

Methods

Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or co-transfected with the IGF-I and FGF-2 gene, encapsulated in alginate and transplanted into osteochondral defects in the knee joints of rabbits in vivo.

Results

After 3 weeks, co-overexpression of IGF-I/FGF-2 improved the macroscopic aspect of defects without affecting the synovial membrane. Immunoreactivity to type-I collagen, an indicator of fibrocartilage, was significantly lower in defects receiving IGF-I/FGF-2 implants. Importantly, combined IGF-I/FGF-2 overexpression significantly improved the histological repair score. Most remarkably, such enhanced cartilage repair was correlated with a 2.1-fold higher proteoglycan content of the repair tissue. Finally, there were less degenerative changes in the cartilage adjacent to the defects treated with IGF-I/FGF-2 implants.

Conclusion

The data demonstrate that combined gene delivery of therapeutic growth factors to cartilage defects may have value to promote cartilage repair. The results also suggest a protective effect of IGF-I/FGF-2 co-overexpression on the neighbouring articular cartilage. These findings support the concept of implementing gene transfer strategies for articular cartilage repair in a clinical setting.     

One-step osteochondral repair with cartilage fragments in a composite scaffold

Purpose

This study proposes a single-step therapeutic approach for osteochondral defects using autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA) derivative, human fibrin glue (FG) and autologous platelet-rich-plasma (PRP), in a rabbit model. The aim is to demonstrate the in vitro outgrowth of chondrocytes from cartilage fragments and the in vivo formation of a functional repair tissue.

Methods

In vitro: minced articular cartilage was loaded onto two different types of scaffold (paste or membrane) according to two different HA preparations (injectable HA-derivative or HA-derivative felt). In vivo: trochlear osteochondral defects were created in 50 adult rabbits, which were then assigned to 5 different treatment groups: cartilage fragments loaded onto membrane scaffolds with FG (Group 1) or without FG (Group 2); membrane scaffolds alone with FG (Group 3) or without FG (Group 4); empty defects (Group 5). Membrane scaffolds were used “in vivo” for simpler preparation and better adhesive properties. Repair processes were evaluated histologically and by immunohistochemistry at 1, 3, and 6 months.

Results

An in vitro time-dependent cell outgrowth from cartilage fragments was observed with both types of scaffolds. At 6 months, in vivo, cartilage fragment-loaded scaffolds induced significantly better repair tissue than the scaffold alone using histological scoring. Repair in Group 2 was superior to that in any of the control groups (p < 0.05).

Conclusion

Autologous cartilage fragments loaded onto an HA felt/FG/PRP-scaffold provided an efficient cell source, and allowed for an improvement of the repair process of ostechondral defects in a rabbit model. Human FG, however, hampered the rabbit healing process. These results may have clinical relevance as they show the potential of a novel one-stage repair technique for osteochondral defects.     

Effect of autologous platelet-rich plasma on the repair of full-thickness articular defects in rabbits

Purpose

To assess the effect of autologous platelet-rich plasma on the repair of full-thickness articular cartilage lesions in immature rabbits. To that end, the samples were studied using macroscopic, microscopic and biomechanical techniques.

Methods

Twenty-four 11-week-old New Zealand rabbits were divided into two groups based on the treatment (physiological saline serum PCB, autologous platelet-rich plasma PRP). Cartilage lesions were drilled in medial femoral condyle of these rabbits. Other 12 rabbits were under the same conditions, but they did not suffer any lesion and treatment (control group CTR). The three groups were divided into two subgroups, depending on the age at the time of killing (16 and 19 weeks old).

Results

The CTR group showed the best possible value in the macroscopic and microscopic evaluation. Meanwhile, the PCB and PRP group values were lower than the CTR group values, at two times of the study, but similar to each other at 19 weeks. In the biomechanical study, at 16 weeks, the CTR and PCB groups behaved similarly, with values above PRP group values, while at 19 weeks, CTR group showed higher values than PCB and PRP groups, and there were no differences between these values.

Conclusions

The evolution of the tissue treated with autologous PRP showed a positive tendency over time, while the PCB group was negative. Nevertheless, at 19 weeks of age, the PRP treatment did not show better results than the PCB, both showing the characteristics of fibrocartilaginous tissue. Likewise, none of the two treatments produced a repair tissue as the healthy cartilage.     

Implantation of tissue-engineered cartilage-like tissue for the treatment for full-thickness cartilage defects of the knee

Purpose

The purposes of this study were to evaluate early- to midterm clinical results after implantation of tissue-engineered cartilage-like tissue for the treatment for full-thickness cartilage defects of the knee and to identify the factors affecting the final clinical results.

Methods

Tissue-engineered cartilage-like tissue was prepared by culturing autologous chondrocytes in atelocollagen gel for 3–4 weeks. A total of 73 knees of 72 patients with full-thickness cartilage defects were implanted with this tissue-engineered cartilage-like tissue. The follow-up of these patients for >5 years (range 5–11 years, median 8.0 years) is reported. The patients were evaluated clinically using a rating scale, as well as arthroscopically, biomechanically, and histologically. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used to quantify the magnetic resonance imaging (MRI) findings of the lesions. The patient or defect factors influencing the final clinical outcomes were also investigated.

Results

Clinical rating improved significantly after implantation of tissue-engineered cartilage-like tissue. Arthroscopic findings at 2 years after implantation were graded as normal or nearly normal according to the International Cartilage Repair Society (ICRS) scale in 64 of 73 knees (87.7 %). Biomechanically, stiffness of the graft almost equalled the surrounding normal cartilage (87.9–102.5 %) at 2 years after implantation. Histologically, overall assessment of the repaired tissue by ICRS Visual Assessment Scale II was 70.4 ± 20.8. The average MOCART score was 13.5 ± 11.3 (0–45) preoperatively, 66.6 ± 16.8 (10–90) at 1 year after implantation, 70.4 ± 16.1 (15–90) at 2 years after implantation, and 72.5 ± 17.4 (15–95) at the final follow-up, indicating that MRI results were maintained. Among the factors investigated, only arthroscopic grade of the repaired lesion at 2 years after implantation was significantly correlated with the final clinical scores.

Conclusions

Implantation of tissue-engineered cartilage-like tissue for the cartilage defects of the knee was effective in short- to midterm post-operatively. This procedure can be proposed as one option for repairing full-thickness cartilage defect of the knee.

Level of evidence

IV.     

Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model

Purpose

The integration of regenerated cartilage with surrounding native cartilage is a major challenge for the success of cartilage tissue-engineering strategies. The purpose of this study is to investigate whether incorporation of the power of mesenchymal stem cell (MSC) sheet to MSCs-loaded bilayer poly-(lactic-co-glycolic acid) (PLGA) scaffolds can improve the integration and repair of cartilage defects in a rabbit model.

Methods

Rabbit bone marrow-derived MSCs were cultured and formed cell sheet. Full-thickness cylindrical osteochondral defects (4 mm in diameter, 3 mm in depth) were created in the patellar groove of 18 New Zealand white rabbits and the osteochondral defects were treated with PLGA scaffold (n = 6), PLGA/MSCs (n = 6) or MSC sheet-encapsulated PLGA/MSCs (n = 6). After 6 and 12 weeks, the integration and tissue response were evaluated histologically.

Results

The MSC sheet-encapsulated PLGA/MCSs group showed significantly more amounts of hyaline cartilage and higher histological scores than PLGA/MSCs group and PLGA group (P < 0.05). In addition, the MSC sheet-encapsulated PLGA/MCSs group showed the best integration between the repaired cartilage and surrounding normal cartilage and subchondral bone compared to other two groups.

Conclusions

The novel method of incorporation of MSC sheet to PLGA/MCSs could enhance the ability of cartilage regeneration and integration between repair cartilage and the surrounding cartilage. Transplantation of autologous MSC sheet combined with traditional strategies or cartilage debris might provide therapeutic opportunities for improving cartilage regeneration and integration in humans.     

Repair tissue quality after arthroscopic autologous collagen-induced chondrogenesis (ACIC) assessed via T2* mapping

Objective

A novel single-stage approach using arthroscopic microdrilling and atelocollagen/fibrin-gel application is employed for cartilage repair of the knee. The purpose of our study was to investigate the morphological and biochemical MRI outcome after this technique.

Materials and methods

A retrospective case series of ten patients (mean age 45 years) with symptomatic chondral defects in the knee who were treated arthroscopically with microdrilling and atelocollagen application was analyzed. All defects were ICRS grade III or IV and the sizes were 2–8 cm² intra-operatively. All patients underwent morphological MRI and T2-star mapping at 1.5 T at 1-year follow-up. The magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. T2* relaxation time values of repair tissue and a healthy native cartilage area was assessed by means of region of interest analysis on the T2* maps.

Results

The mean MOCART score at 1-year follow-up was 71.7?±?21.0 ranging from 25 to 95. The mean T2* relaxation times were 30.6?±?11.3 ms and 28.8?±?6.8 ms for the repair tissue and surrounding native cartilage, respectively. The T2* ratio between the repair tissue and native cartilage was 105 %?±?30 %, indicating repair tissue properties similar to native cartilage.

Conclusions

An arthroscopic single-stage procedure using microdrilling in combination with atelocollagen gel and fibrin-glue can provide satisfactory MRI results at 1-year follow-up, with good cartilage defect filling. The T2* values in the repair tissue achieved similar values compared to normal hyaline cartilage.

     

Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant

Purpose

The aim of our study was to analyse the clinical and histological outcome after the treatment of focal cartilage defects in non-degenerative and degenerative knees with bone marrow stimulation and subsequent covering with a cell-free resorbable polyglycolic acid–hyaluronan (PGA-HA) implant immersed with autologous platelet-rich plasma (PRP).

Methods

Fifty-two patients (mean age 44 years) with focal chondral defects in radiologically confirmed non-degenerative or degenerative knees were subjected to subchondral drilling arthroscopically. Subsequently, defects were covered with the PGA-HA implant immersed with autologous PRP. At 2-year follow-up, the patients’ situation was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and compared to the pre-operative situation and 3–12-month follow-up. Biopsies (n = 4) were harvested at 18–24 months after implantation and were analysed by histology and collagen type II immune staining.

Results

At 1- and 2-year follow-up, the KOOS showed clinically meaningful and significant (p < 0.05) improvement in all subcategories compared to baseline and to 3-month follow-up. There were no differences in KOOS data obtained after 2 years compared to 1 year after the treatment. Histological analysis of the biopsy tissue showed hyaline-like to hyaline cartilage repair tissue that was rich in cells with a chondrocyte morphology, proteoglycans and type II collagen.

Conclusions

Covering of focal cartilage defects with the PGA-HA implant and PRP after bone marrow stimulation improves the patients’ situation and has the potential to regenerate hyaline-like cartilage.

Level of evidence

Case series, Level IV.     

Chevron-type medial malleolar osteotomy: a functional, radiographic and quantitative T2-mapping MRI analysis

Purpose

The purpose of this study was to retrospectively evaluate a large series of patients for functional, radiographic and MRI outcomes after a Chevron-type medial malleolar osteotomy.

Methods

Sixty-two patients underwent a Chevron-type medial malleolar osteotomy with a median follow-up of 34.5 months. Standard digital radiographs were used to determine bony union and the angle of the osteotomy relative to the longitudinal axis of the tibia. Morphologic and quantitative T2-mapping MRI was also analysed in 32 patients.

Results

Fifty-eight patients (94 %) reported being asymptomatic at the site of the medial malleolar osteotomy. The median time to healing on standard radiograph was 6 weeks (range, 4–6 weeks) with an angle of 31.7° ± 6.9°. Quantitative T2-mapping MRI analysis demonstrated that the deep half of interface repair tissue had relaxation times that were not significantly different from normal tibial cartilage. In contrast, interface repair tissue in the superficial half demonstrated significant prolongation from normal relaxation time values, indicating a more fibrocartilaginous repair. Four patients (6 %) reported pain post-operatively.

Conclusion

A Chevron-type medial malleolar osteotomy demonstrates satisfactory healing and fixation, with fibrocartilaginous tissue evident superficially at the osteotomy interface. Further investigation is warranted in the form of longitudinal study to assess the long-term outcomes of medial malleolar osteotomy.

Level of evidence

IV.     

Feasibility of in vivo diffusion tensor imaging of articular cartilage with coverage of all cartilage regions

Objectives

To investigate the value of diffusion tensor imaging (DTI) of articular cartilage to differentiate healthy from osteoarthritis (OA) subjects in all cartilage regions.

Methods

DTI was acquired sagittally at 7 T in ten healthy and five OA (Kellgren-Lawrence grade 2) subjects with a line scan diffusion tensor sequence (LSDTI). Three healthy volunteers and two OA subjects were examined twice to assess the test-retest reproducibility. Averaged mean diffusivity (MD) and fractional anisotropy (FA) were calculated in each cartilage region (femoral trochlea, lateral and medial femoral condyles, patella, and lateral and medial tibia).

Results

The test-retest reproducibility was 2.9 % for MD and 5.6 % for FA. Averaged MD was significantly increased (+20 %, p?<?0.05) in the OA subjects in the lateral femoral condyle, lateral tibia and the femoral trochlea compartments. Averaged FA presented a trend of lower values in the OA subjects (-12 %), which was only significant for the lateral tibia.

Conclusions

In vivo DTI of articular cartilage with coverage of all cartilage regions using an LSDTI sequence is feasible, shows excellent reproducibility for MD and FA, and holds potential for the diagnosis of OA.

Key points

? DTI of articular cartilage is feasible at 7 T in all cartilage regions ? DTI of articular cartilage can potentially differentiate healthy and OA subjects     

Radiologische Bildgebung der Kniegelenkarthrose

Clinical/methodical issue

Osteoarthritis is the most common degenerative age-related joint disease leading to typical degradation of articular cartilage with severe pain and limitation of joint motion.

Standard radiological methods

Although knee radiographs are widely considered as the gold standard for the assessment of knee osteoarthritis in clinical and scientific settings they increasingly have significant limitations in situations when resolution and assessment of cartilage is required.

Methodical innovations

Analysis of osteoarthritis of the knee with conventional x-ray is associated with many technical limitations and is increasingly being replaced by high-quality assessment using magnetic resonance imaging (MRI) or sonography both in the clinical routine and scientific studies.

Performance

Novel imaging modalities such as MRI or ultrasound enable in vivo visualization of the quality of the cartilaginous structure and bone as well as all articular and periarticular tissue. Therefore, the limitations of radiographs in assessment of knee osteoarthritis could be overcome by these techniques. This review article aims to provide insights into the most important radiological features of knee osteoarthritis and systematic visualization with different imaging approaches.

Practical recommendations

The demographic development in western industrialized countries predicts an increase of ageing-related osteoarthritis of the knee for the next decades. A systematic radiological evaluation of patients with knee osteoarthritis includes the assessment of the periarticular soft tissue, cartilaginous thickness, cartilage volume, possible cartilage defects, the macromodular network of hyaline cartilage, bone marrow edema, menisci and articular ligaments. Modern imaging modalities, such as MRI and sonography allow the limitations of conventional radiography to be overcome and to visualize the knee structures in great detail to quantitatively assess the severity of knee osteoarthritis.     

Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration

Purpose

Osteochondral defects (i.e., defects which affect both the articular cartilage and underlying subchondral bone) are often associated with mechanical instability of the joint and therefore with the risk of inducing osteoarthritic degenerative changes. This review addresses the current surgical treatments and most promising tissue engineering approaches for articular cartilage and subchondral bone regeneration.

Methods

The capability to repair osteochondral or bone defects remains a challenging goal for surgeons and researchers. So far, most clinical approaches have been shown to have limited capacity to treat severe lesions. Current surgical repair strategies vary according to the nature and size of the lesion and the preference of the operating surgeon. Tissue engineering has emerged as a promising alternative strategy that essentially develops viable substitutes capable of repairing or regenerating the functions of damaged tissue.

Results

An overview of novel and most promising osteochondroconductive scaffolds, osteochondroinductive signals, osteochondrogenic precursor cells, and scaffold fixation approaches are presented addressing advantages, drawbacks, and future prospectives for osteochondral regenerative medicine.

Conclusion

Tissue engineering has emerged as an excellent approach for the repair and regeneration of damaged tissue, with the potential to circumvent all the limitations of autologous and allogeneic tissue repair.

Level of evidence

Systematic review, Level III.     

Microfracture combined with osteochondral paste implantation was more effective than microfracture alone for full-thickness cartilage repair

Purpose

The aim of this study was to evaluate whether the microfracture combined with osteochondral paste implantation could promote the quality of the regenerated tissue in the knee joints of rabbits.

Methods

Sixty-six New Zealand white rabbits were used. Bilateral knee joints from the same rabbit were randomly divided into experimental group and microfracture group. An articular cartilage defect was established in the femoral trochlear groove. In the experimental group, the defect was microfractured and covered with osteochondral paste harvested from the intercondylar notch. The regenerated tissues were harvested for gross morphology, histology, biochemistry and gene expression analysis at 4, 8 and 12 weeks postoperatively.

Results

The regenerated tissue had a slowly mature process in both groups. At 12 weeks, the regenerated tissue in the experimental group appeared much more thicker and white with higher percentages of defect filling macroscopically. In histology, the experimental group found a majority of hyaline-like regenerate tissue with intense Safranin-O and collagen type II staining, while fibrocartilage-like tissue was mostly seen in the microfracture group with poor Safranin-O and collagen type II staining. The experimental group had higher Wakitani scores and narrower acellular zones than those in the microfracture group (P < 0.05). For biochemical analysis, both the GAG content and the DNA-normalized GAG content saw a time-dependent increase with a much higher value found in the experimental group at 8 and 12 weeks (P < 0.05). On the contrary, the total DNA content decreased with time in both groups, and the difference between the two groups was only found at 4 and 8 weeks (P < 0.05). For gene expression analysis, the experimental group had much higher expression levels than the microfracture group as for collagen type II and aggrecan, but not for collagen type I.

Conclusion

Microfracture combined with paste implantation can result in improved quality of the reparative tissue and may have a positive effect on the integration to the surrounding cartilage in the rabbit model. The technique offers a promising treatment option for cartilage defects and improves the regeneration of articular cartilage for patients with painful chondral lesions.     

Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee

Purpose

To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee.

Methods

Thirty-two patients aged 15–51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system.

Results

The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow-up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%).

Conclusions

This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure.

Level of evidence

IV.     

A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies

Purpose

To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide^®) scaffold.

Methods

By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water–dioxane–PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT–PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide^® scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O’Driscoll score.

Results

In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide^® scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide^® scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells.

Conclusion

The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide^® scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide^® scaffold with cells.     

Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model

Purpose

The objective of this study was to examine whether different mechanical modifications and/or impregnation of hyaluronic acid (HA) might enhance aragonite-based scaffold properties for the regeneration of cartilage and bone in an animal model.

Methods

Bi-phasic osteochondral scaffolds were prepared using coralline aragonite with different modifications, including 1- to 2-mm-deep drilled channels in the cartilage phase (Group 1, n = 7) or in the bone phase (Group 2, n = 8), and compared with unmodified coral cylinders (Group 3, n = 8) as well as empty control defects (Group 4, n = 4). In each group, four of the implants were impregnated with HA to the cartilage phase. Osteochondral defects (6 mm diameter, 8 mm depth) were made in medial and lateral femoral condyles of 14 goats, and the scaffolds were implanted according to a randomization chart. After 6 months, cartilage and bone regeneration were evaluated macroscopically and histologically by an external laboratory.

Results

Group 1 implants were replaced by newly formed hyaline cartilage and subchondral bone (combined histological evaluation according to the ICRS II-2010 and O’Driscoll et al. 34 ± 4 n = 7). In this group, the cartilaginous repair tissue showed a smooth contour and was well integrated into the adjacent native cartilage, with morphological evidence of hyaline cartilage as confirmed by the marked presence of proteoglycans, a marked grade of collagen type II and the absence of collagen type I. The average scores in other groups were significantly lower (Group 2 (n = 8) 28.8 ± 11, Group 3 (n = 8) 23 ± 9 and Group 4 (empty control, n = 4) 19.7 ± 15).

Conclusions

The implants with the mechanical modification and HA impregnation in the cartilage phase outperformed all other types of implant. Although native coral is an excellent material for bone repair, as a stand-alone material implant, it does not regenerate hyaline cartilage. Mechanical modification with drilled channels and impregnation of HA within the coral pores enhanced the scaffold’s cartilage regenerative potential. The modified implant shows young hyaline cartilage regeneration. This implant might be useful for the treatment of both chondral and osteochondral defects in humans.     

Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC)

Purpose

The purpose of this study is to evaluate clinical and radiological outcomes of patients treated with autologous matrix-induced chondrogenesis (AMIC) for full-thickness chondral and osteochondral defects of the femoral condyles and patella.

Method

A retrospective evaluation of clinical and radiographic outcomes of patients treated with AMIC for chondral and osteochondral full-thickness cartilage defects of the knee was performed with a mean follow-up of 28.8 ± 1.5 months (range, 13–51 months).

Results

Significant improvements in clinical outcome scores (IKDC, Lysholm, Tegner, and VAS pain score) were noted. The largest improvements were seen in the osteochondral subgroup (mean age 25.9 years), whereas patients treated for chondral defects in the patellofemoral joint and on the femoral condyles improved less. Patients in all groups were generally satisfied with their results. MRI evaluation showed that tissue filling was present but generally not complete or homogenous.

Conclusions

AMIC is a safe procedure and leads to clinical improvement of symptomatic full-thickness chondral and osteochondral defects and to regenerative defect filling. The value of AMIC relative to other cartilage repair procedures and to the natural course remains undefined.

Level of evidence

Case series, Level IV.     

Cell-free repair of small cartilage defects in the Goettinger minipig: which defect size is possible?

Purpose

Cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with cell-free collagen type-I gel plugs of three different sizes.

Methods

In 6 adult Goettinger minipigs, three full-thickness chondral defects were created in the trochlear groove of one knee of the hind leg. These defects were treated with a cell-free collagen type-I gel plug of 8, 10, or 12 mm diameter. All animals were allowed unlimited weight bearing. After 1 year, the animals were killed. Immediately after recovery, a non-destructive biomechanical testing was performed. The repair tissue quality was evaluated immunohistologically, collagen type-II protein was quantified, and a semiquantitative score (O’Driscoll score) was calculated.

Results

After 1 year, a high number of cells migrated into the initially cell-free collagen gel plugs and a hyaline-like repair tissue had been created. The O’Driscoll scores were: 8 mm, 21.2 (SD, 2.8); 10 mm, 21.5 (SD, 1.6); and 12 mm, 22.3 (SD, 1.0). The determination of the e-modulus, creep and relaxation revealed that mechanical properties of the two smaller defects were closer to unaffected hyaline cartilage.

Conclusions

As cell-free collagen type-I gel plugs of all three different sizes created hyaline-like repair tissue, this system seems suitable for the treatment of even larger defects.     

Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs

Purpose

The aim of this work is to investigate the feasibility of non-autologous transplantation of human mesenchymal stem cells (hMSCs) with or without differentiation for the regeneration of osteochondral defects in rabbits using a biphasic composite construct composed of platelet-rich fibrin glue (PR-FG) and hydroxyapatite.

Methods

After isolation and culture, hMSCs were seeded on biphasic composite constructs (hydroxyapatite + PR-FG) and transplanted into osteochondral defects of adult New Zealand white rabbits. Treatment of individual defects was applied by random assignment to one of five groups: (1) control, defects untreated; (2) hydroxyapatite, defects filled with hydroxyapatite only; (3) hydroxyapatite + PR-FG, defects filled with a composite of hydroxyapatite and PR-FG; (4) hydroxyapatite + PR-FG + undifferentiated hMSCs; and (5) hydroxyapatite + PR-FG + differentiated hMSCs. Rabbits were killed at 4 or 8 weeks post-surgery, at which time osteochondral repair was macroscopically and histologically evaluated and scored using the modified International Cartilage Repair Society scoring system.

Results

The group in which defects were seeded with differentiated hMSCs (group 5) showed superior healing of osteochondral defects based on macroscopic and histological observations compared to other groups. Specifically, 8 weeks after implantation, defects were filled with more hyaline-like cartilage and were better integrated with the surrounding native cartilage. The histological scores were significantly better than those of other groups (16.3 at 8 weeks, p < 0.01).

Conclusion

Xenogeneic transplantation of differentiated hMSCs using a biphasic composite construct effectively repaired osteochondral defect in a rabbit model. Differentiated hMSCs showed superior healing of chondral lesion to undifferentiated hMSCs.     

Clinical and MRI evaluation of medium- to long-term results after autologous osteochondral transplantation (OCT) in the knee joint

Purpose

Autologous osteochondral transplantation (OCT) is one of the surgical options currently used to treat cartilage defects. It is the only cartilage repair method that leads to a transfer of hyaline cartilage repair tissue. The purpose of this study was to evaluate the magnetic resonance observation of cartilage repair tissue (MOCART) score, the 3D MOCART score and various clinical scores in patients after OCT in knee joints.

Methods

Two women and eight men were evaluated 6–9 years (median 7.2 years) after OCT on the femoral condyle of the knee joint. All patients were evaluated by magnetic resonance imaging (MRI) measurement, using a 3.0 T Scanner with different cartilage-specific sequences. Clinical assessment included the knee injury and osteoarthritis outcome score (KOOS), the international knee documentation committee (IKDC) subjective knee form, the Noyes sport activity rating scale and the Tegner activity score. For MRI evaluation, the MOCART score and 3D MOCART score were applied.

Results

Clinical long-term results after OCT showed median values of 77 (range 35.7–71.4) for the IKDC; 50 (6.3–100), 66.7 (30.6–97.2), 65 (0–75), 57.1 (35.7–71.4) and 80.9 (30.9–100) for the KOOS subscales (quality of life, pain sports, symptoms and activity of daily living); 61.4 (22.3–86.2) for the Noyes scale; and 3 (0–6) for the Tegner activity score. The median MOCART score was 75 (30–90) after both 1 and 2 years and 57.5 (35–90) after 7 years, as assessed by different cartilage-specific sequences. The 3D MOCART score showed values of 70 (50–85) and 60 (50–80) in the two different isotropic sequences after 7 years.

Conclusion

The MOCART and 3D MOCART scores are applicable tools for patient follow-up after OCT. Post-operative follow-up assessments would also benefit from the inclusion of OCT-specific parameters. Long-term results after OCT reflect an impairment in clinical scores in the first 2 years with good results during follow-up. Stable conditions were observed between 2 and 7 years after surgery. The filling of the defects and the cartilage interface appeared good at MRI evaluation after the first 2 years, but cartilage loss was observed between the medium- and long-term follow-ups. Isotropic imaging with multiplanar reconstruction is useful for daily clinical use to assess bony cylinders in cartilage repair, especially in combination with the 3D MOCART.

Level of evidence

Retrospective therapeutic study, Level IV.     

The relationship between patellofemoral and tibiofemoral morphology and gait biomechanics following arthroscopic partial medial meniscectomy

Purpose

To examine the relationship between tibiofemoral and patellofemoral joint articular cartilage and subchondral bone in the medial and gait biomechanics following partial medial meniscectomy.

Methods

For this cross-sectional study, 122 patients aged 30–55 years, without evidence of knee osteoarthritis at arthroscopic partial medial meniscectomy, underwent gait analysis and MRI on the operated knee once for each sub-cohort of 3 months, 2 years, or 4 years post-surgery. Cartilage volume, cartilage defects, and bone size were assessed from the MRI using validated methods. The 1st peak in the knee adduction moment, knee adduction moment impulse, 1st peak in the knee flexion moment, knee extension range of motion, and the heel strike transient from the vertical ground reaction force trace were identified from the gait data.

Results

Increased knee stance phase range of motion was associated with decreased patella cartilage volume (B = ?17.9 (95 % CI ?35.4, ?0.4) p = 0.045) while knee adduction moment impulse was associated with increased medial tibial plateau area (B = 7.7 (95 % CI 0.9, 13.3) p = 0.025). A number of other variables approached significance.

Conclusions

Knee joint biomechanics exhibited by persons who had undergone arthroscopic partial meniscectomy gait may go some way to explaining the morphological degeneration observed at the patellofemoral and tibiofemoral compartments of the knee as patients progress from surgery.

Level of evidence

III.