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.     

Human cartilage fragments in a composite scaffold for single-stage cartilage repair: an in vitro study of the chondrocyte migration and the influence of TGF-β1 and G-CSF

Purpose

Minced chondral fragments are becoming popular as a source of cells for cartilage repair, as a growing interest is developing towards one-stage procedures to treat cartilage lesions. The purpose of this study is to (A) compare cell outgrowth from cartilage fragments of adult and young donors using two different types of scaffolds and (B) evaluate the influence of transforming-growth-factor-β1 (TGF-β1) and granulocyte colony-stimulating factor (G-CSF) on chondrocyte behaviour.

Methods

In part (A) cartilage fragments from adult and young donors were either loaded onto an HA-derivative injectable paste scaffold or onto an HA-derivative membrane scaffold. Construct sections were then examined for cell counting after 1, 2 and 3 months. In part (B) only membrane scaffolds were prepared using cartilage fragments from young donors. Constructs were cultured either in standard growth medium or in the presence of specific growth factors, such as TGF-β1 or G-CSF or TGF-β1 + G-CSF. After 1 month, construct sections were examined for cell counting. Expression of chondrocyte markers (SOX9, CD151, CD49c) and proliferative markers (β-catenin, PCNA) was assessed using immunofluorescence techniques, both in unstimulated construct sections and in cells from unstimulated and stimulated construct cultures.

Results

Part (A): histological analysis showed age-dependent and time-dependent chondrocyte migration. A significant difference (p < 0.05) was observed between young and older donors at the same time point. No difference was detected between the two types of scaffolds within the same group at the same time point. Part (B): after 1 month, the number of migrating cells/area significantly increased due to exposure to TGF-β1 and/or G-CSF (p < 0.05). Immunofluorescence revealed that outgrowing cells from unstimulated scaffold sections were positive for SOX9, CD151, CD49c and G-CSF receptor. Immunofluorescence of cells from construct cultures showed an increase in β-catenin in all stimulated groups and an increased PCNA expression in G-CSF-exposed cultures (p < 0.05).

Conclusion

Outgrowing cells may represent a subset of chondrocytes undergoing a phenotypic shift towards a proliferative state. TGF-β1, and to a greater extent G-CSF, may accelerate this outgrowth. The clinical relevance of this study may involve a potential future clinical application of scaffolds preloaded with growth factors as an additional coating for chondral fragments. Indeed, a controlled delivery of G-CSF, widely employed in various clinical settings, might improve the repair process driven by minced human cartilage fragments during one-stage cartilage repair.     

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.     

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.     

Increased chondrocyte seeding density has no positive effect on cartilage repair in an MPEG-PLGA scaffold

Purpose

This study investigates the effect of cell seeding density on cartilage repair in matrix-assisted chondrocyte implantation in vitro and in vivo.

Methods

In vitro: Four different cell seeding densities of human chondrocytes were seeded onto a porous methoxy-polyethylene glycol-polylactic-co-glycolic acid scaffold (MPEG-PLGA) polymer scaffold ASEED? (1.2 × 10⁶, 4.0 × 10⁶, 1.2 × 10⁷ and 2.0 × 10⁷ cells/cm³). The cartilage repair response was evaluated by relative gene expression of the chondrogenic markers sox9, collagen types I, II and X, and aggrecan, total DNA content and sulphated glycosaminoglycan synthesis. In vivo: Using a New Zealand white rabbit intercondylar osteochondral defect model, three different cell seeding densities (1.2 × 10⁶, 4.0 × 10⁶ and 1.2 × 10⁷ cells/cm³) were tested with an empty scaffold as control. The cartilage repair response was evaluated using O’Driscoll score.

Results

In vitro: A significant difference (p < 0.05) in total DNA content was found at day 2 but not at day 7. The low cell seeding densities yielded the highest GAG content (p < 0.001) at day 7. Collagen type I was highest (p < 0.01) at the lowest density at day 7. In vivo: No significant difference was found between the 4 groups.

Conclusions

No positive effect on cartilage repair was found using increased cell seeding density.

Level of evidence

Controlled experimental study, Level II.     

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.     

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.     

The effects of the synovium on chondrocyte growth: an experimental study

Purpose

The objective of this study was to evaluate the effects of synovium on the proliferation of the cartilage tissue and chondrocytes using a rabbit knee model as an in vivo synovial culture medium.

Methods

Twelve New Zealand rabbits were used as the animal model in this investigation. Standard size chondral and osteochondral cartilage grafts were taken from, respectively, the left and right knees of all the animals. Two groups of 6 animals were formed: in Group I (synovium group), grafts were placed into the synovial tissue and in group II (patellar tendon group) behind the patellar tendon of the corresponding knees. After 4 months, samples were collected and evaluated macroscopically by measuring their dimensions (vertical = D1, horizontal = D2, and depth = D3) and volumes, and histologically by counting the chondrocyte number using camera lucida method.

Results

Macroscopically, the increase in average D1, D2, and D3 measurements and volume in the osteochondral specimens were significantly higher compared to the chondral specimens in both groups (P < 0.05). However, no significant difference was observed between the two groups in terms of macroscopic values. Histologically, the mean chondrocyte counts in osteochondral and chondral specimens for Group I (synovium) were 20.2 and 18.1, and for Group II (patellar tendon) were 18.7 and 15.6, respectively. The mean number of chondrocytes was found to be significantly higher in osteochondral specimens than that of chondral specimens in either group (P < 0.05). Overall average chondrocyte count was significantly higher for Group I compared to Group II (P < 0.05).

Conclusion

Transplantation of the cartilage grafts into the synovial tissue in rabbit knees significantly enhanced the chondrocyte production compared with the group where the grafts were transplanted into intra-articular patellar tendon. The results of this study indicate that native synovial tissue may have the potential to be used as an in vivo culture medium for osteochondral tissue growth.     

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.     

Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee

Purpose

Large osteochondral defects involve two different tissues characterized by different intrinsic healing capacity. Different techniques have been proposed to treat these lesions with results still under discussion. The aim of the study is to evaluate the clinical outcome of 19 patients treated with a type I collagen–hydroxyapatite nanostructural biomimetic osteochondral scaffold at minimum follow-up of 2 years.

Methods

Twenty lesions, 19 patients were treated with this scaffold implantation. The lesions size went from 4 to 8 cm² (mean size 5.2 ± 1.6 cm²). All patients were clinically evaluated using the International Repair Cartilage Society score, the Tegner Score and EQ-VAS. MRI was performed at 12 and 24 months after surgery and then every 12 months and evaluated with magnetic resonance observation of cartilage repair tissue scoring scale.

Results

The IKDC subjective score improved from a mean score of 35.7 ± 6.3 at the baseline evaluation to 67.7 ± 13.4 at 12-month follow-up (p < 0.0005). A further improvement was documented from 12 to 24 months (mean score of 72.9 ± 12.4 at 24 months) (p < 0.0005). The IKDC objective score confirmed the results. The Tegner activity score improvement was statistically significant (p < 0.0005). The EQ-VAS showed a significant improvement from 3.15 ± 1.09 to 7.35 ± 1.14 (p < 0.0005) at 2-year follow-up. The lesion’ site seems to influence the results showing a better outcome in the patients affected in the medial femoral condyle.

Conclusions

The use of the MaioRegen scaffold is a good procedure for the treatment for large osteochondral defects where other classic techniques are difficult to apply. It is an open one-step surgery with promising stable results at medium follow-up.

Level of evidence

IV.     

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.     

The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage

Purpose

The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee.

Methods

The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2?years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24?months of follow-up.

Results

A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case.

Conclusions

The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2?years of follow-up.

Level of evidence

IV.     

Autologous collagen-induced chondrogenesis technique (ACIC) for the treatment of chondral lesions of the talus

Purpose

Autologous collagen-induced chondrogenesis technique (ACIC) combines microfractures with the use of an injectable atelocollagen matrix that allows performing the whole cartilage repair treatment arthroscopically. The aim of this study was to evaluate the in vitro cytocompatibility of this biomaterial using human bone marrow mesenchymal stem cells and human chondrocytes. Moreover, the preliminary data of five patients affected by chondral lesion of the talus treated with the ACIC technique are shown.

Methods

Human bone marrow mesenchymal stem cells and human chondrocytes were seeded on solid and pre-solid atelocollagen scaffolds. Cell–scaffold constructs were cultured for 7 days and then prepared for histological analyses. Arthroscopic ACIC was performed in five patients affected by chondral lesions of the talus; they were clinically evaluated with AOFAS, VAS and Tegner score before and then after 6 months from surgery.

Results

In vitro results showed that both bone marrow mesenchymal stem cells and chondrocytes were able to efficiently colonize the whole construct, from the surface to the core, only when seeded on the pre-solid atelocollagen scaffold, but not on its solid form. No adverse events were observed in the patients treated with the ACIC technique; a significant improvement in VAS pain scale and in AOFAS score was found at 6 months follow up.

Conclusion

Injectable atelocollagen can be considered a feasible scaffold for cartilage repair treatment, in particular if used in its pre-solid form. ACIC leads to good clinical results in the treatment for chondral lesions of the talus even if longer follow-up and a higher number of patients are necessary to confirm these data.

Level of evidence

IV.     

Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage

Purpose

Due to the attractive properties of poly(l-lactic acid) (PLLA) for tissue engineering, the aim was to determine the growth and differentiation capacity of mesenchymal stromal cells (MSCs) in PLLA scaffolds and their potential use in the treatment of cartilage diseases.

Methods

MSCs were cultured in PLLA films and thin porous membranes to study adherence and proliferation. Permeability and porosity were determined for the different scaffolds employed. The optimal conditions for cell seeding were first determined, as well as cell density and distribution inside the PLLA. Scaffolds were then maintained in expansion or chondrogenic differentiation media for 21 days. Apoptosis, proliferation and chondrogenic differentiation was assessed after 21 days in culture by immunohistochemistry. Mechanical characteristics of scaffolds were determined before and after cell seeding.

Results

MSCs uniformly adhered to PLLA films as well as to porous membranes. Proliferation was detected only in monolayers of pure PLLA, but was no longer detected after 10 days. Mechanical characterization of PLLA scaffolds showed differences in the apparent compression elastic modulus for the two sizes used. After determining high efficiencies of seeding, the production of extracellular matrix (ECM) was determined and contained aggrecan and collagens type I and X. ECM produced by the cells induced a twofold increase in the apparent elastic modulus of the composite.

Conclusions

Biocompatible PLLA scaffolds have been developed that can be efficiently loaded with MSCs. The scaffold supports chondrogenic differentiation and ECM deposition that improves the mechanics of the scaffold. Although this improvement does not met the expectations of a hyaline-like cartilage ECM, in part due to the lack of a mechanical stimulation, their potential use in the treatment of cartilage pathologies encourages to improve the mechanical component.     

Platelet-rich plasma activation in combination with biphasic osteochondral scaffolds–conditions for maximal growth factor production

Purpose  

The combination of scaffolds and biological factors may enhance articular cartilage repair. Little is known regarding the activation and subsequent growth factor release of platelet-rich plasma (PRP) in contact with biosynthetic scaffolds. The purpose of this study was i) to identify whether the addition of thrombin was required to activate PRP in the presence of a collagen osteochondral scaffold and ii) to compare the activity of PRP when applied to both collagen- and polylactide-based osteochondral scaffolds.     

In vivo experimental imaging of osteochondral defects and their healing using 99mTc-NTP 15-5 radiotracer

Purpose

A rabbit model of osteochondral defects (OD) and spontaneous healing was longitudinally followed over 12?weeks, by in vivo joint scintigraphy using ^99mTc-NTP 15-5, and histology.

Methods

We used two models, one with one OD (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2 group) in the femoral condyle of one knee, with the contralateral knees serving as the reference. A serial longitudinal imaging study was performed with the scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake) determined at each time-point.

Results

ODs were imaged as radioactive defects. The SR was decreased with respective to controls, with values of 0.73?±?0.08 and 0.65?±?0.07 in the OD1 and OD2 groups, respectively, at 4?weeks after surgery. Histology of both OD groups revealed the presence of repair tissue characterized by a small amount of sulphated glycosaminoglycans and collagen.

Conclusion

^99mTc-NTP 15-5 imaging provided quantitative criteria useful for in vivo evaluation of cartilage trauma and healing.     

Failed cartilage repair for early osteoarthritis defects: a biochemical, histological and immunohistochemical analysis of the repair tissue after treatment with marrow-stimulation techniques

Purpose

To examine the entire repair tissue resulting from marrow-stimulation techniques in patients with early osteoarthritis.

Methods

The repair tissue and adjacent articular cartilage after failed marrow-stimulation techniques (microfracture and Pridie drilling) of 5 patients (47–65 years old) with cartilage defects and radiographic early osteoarthritis (Kellgren–Lawrence grading 1 and 2) was removed during total joint arthroplasty (mean time until analysis: 8.8 months), analysed by histology, polarized light microscopy, immunohistochemistry, biochemistry and by histological score systems.

Results

Macroscopic cartilage repair assessment revealed ICRS grades of II (nearly normal) and III (abnormal). Cartilage defects were mostly completely filled with a fibrocartilaginous tissue that had small and large fissures. Cartilage-specific stains of the repair tissue were more intense than the surrounding native cartilage but reduced compared with normal articular cartilage. The subchondral bone was incompletely restored. A new tidemark was absent. The repair tissue always showed positive immunoreactivity for types II and X collagen, and was sometimes positive for type I collagen. Proteoglycan contents of the repair tissue were generally higher than of the surrounding cartilage. The repair tissue was always more cellular than the adjacent articular cartilage. Histological scoring of the repair tissue revealed a mean Sellers score of 17.6 ± 3.0 and an ICRS grading of 7–9.

Conclusion

Failed marrow stimulation of articular cartilage defects in patients with early osteoarthritis is characterized by fibrocartilaginous repair. The balance of cell number to extracellular matrix is shifted towards an increased cell number in this tissue. Articular cartilage repair did not reach the quality of normal hyaline articular cartilage.

Level of evidence

IV.     

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.     

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.     

Trends in the surgical treatment of articular cartilage defects of the knee in the United States

Purpose

The purpose of this study was to evaluate trends in surgical treatment of articular cartilage defects of the knee in the United States.

Methods

The current procedural terminology (CPT) billing codes of patients undergoing articular cartilage procedures of the knee were searched using the PearlDiver Patient Record Database, a national database of insurance billing records. The CPT codes for chondroplasty, microfracture, osteochondral autograft, osteochondral allograft, and autologous chondrocyte implantation (ACI) were searched.

Results

A total of 163,448 articular cartilage procedures of the knee were identified over a 6-year period. Microfracture and chondroplasty accounted for over 98 % of cases. There was no significant change in the incidence of cartilage procedures noted from 2004 (1.27 cases per 10,000 patients) to 2009 (1.53 cases per 10,000 patients) (p = 0.06). All procedures were performed more commonly in males (p < 0.001). This gender difference was smallest in patients undergoing chondroplasty (51 % males and 49 % females) and greatest for open osteochondral allograft (61 % males and 39 % females). Chondroplasty and microfracture were most commonly performed in patients aged 40–59, while all other procedures were performed most frequently in patients <40 years old (p < 0.001).

Conclusions

Articular cartilage lesions of the knee are most commonly treated with microfracture or chondroplasty in the United States. Chondroplasty and microfracture were most often performed in middle-aged patients, whereas osteochondral autograft, allograft, and ACI were performed in younger patients, and more frequently in males.

Level of evidence

Cross-sectional study, Level IV.