Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Purpose

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

Methods

The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.

Results

The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.

Conclusions

Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.

Level of evidence

IV.     

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

Background and purpose

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation.

Material and methods

Daily fractionated irradiation (5?×?3 Gy/week) was given over 1 (days 0–4) or 3 weeks (days 0–4, 7–11, 14–18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose–effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols.

Results

Transplantation of 6?×?10⁶, but not of 3?×?10⁶ bone marrow stem cells on day ??1, +?4, +?8, +?11 or +?15 significantly increased the ED₅₀ values (dose, at which an ulcer is expected in 50?% of the mice); transplantation on day +?2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day ??1, 2 or +?8 significantly, and on day +?4 marginally increased the ED₅₀ values.

Conclusion

Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation.     

Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model

Purpose

The objective of this study was to determine whether using mesenchymal stem cells (MSC) seeded in a collagen type I scaffold would be sufficient to regenerate the torn anterior cruciate ligament (ACL).

Methods

Anterior cruciate ligament transection was performed on both knees in 10 New Zealand rabbits and then repaired with as follows: suture alone (suture-treated group, n = 6), suture associated with collagen type I scaffold (collagen type I scaffold-treated group, n = 8) or suture associated with autologous MSC seeded on collagen type I scaffold (MSC/collagen type I scaffold-treated group, n = 6). At 12-week post-intervention, the animals were killed and the ACLs were characterised macroscopically and histologically. Data of the 3 groups were against normal ACL (normal group, n = 10).

Results

Macroscopic observation found that in MSC/collagen type I scaffold group, 33 % of specimens showed a complete ACL regeneration, with a tissue similar to the normal ACL. Regeneration was not observed in the group treated with suture alone or associated with collagen type I scaffold without cells. In the latter, only a reparative attempt at the ends was observed. Histological analysis of the regenerated ACL showed a tissue with organised collagen and peripheric vessels.

Conclusions

These results provide evidence that the use of MSC seeded in a collagen type I scaffold in the treatment of ACL injuries is associated with an enhancement of ligament regeneration. This MSC-based technique is a potentially attractive tool for improving the treatment of ACL ruptures.     

Treatment of osteochondral defects of the talus in children

Purpose

Osteochondral talar defects are infrequent in children, and little is known about the treatment and clinical outcome of these defects. The purpose of this study was to evaluate the clinical and radiographic outcomes of conservative and primary surgically treated osteochondral talar defects in skeletally immature children.

Methods

Thirty-six (97 %) of 37 eligible patients with a symptomatic primary osteochondral talar defect were evaluated after a median follow-up of 4 years (range 1–12 years). Clinical assessment included the Berndt and Harty outcome question, Ogilvie-Harris score, Visual Analog Scale pain score (at rest, during walking and during running), the American Orthopaedic Foot and Ankle Society (AOFAS) score, and the SF-36. Weight-bearing radiographs were compared with preoperative radiographs with the use of an ankle osteoarthritis classification system.

Results

Ninety-two per cent of the initially conservatively treated children [mean age 13 years (SD 2)] were eventually scheduled to undergo surgery. After fixation of the fragment, seven cases (78 %) reported a good Berndt and Harty outcome, and two cases (22 %) a fair outcome; the median AOFAS score was 95.0 (range 77–100). After debridement and bone marrow stimulation, 13 cases (62 %) reported a good Berndt and Harty outcome, three cases (14 %) a fair outcome, and five cases (24 %) a poor outcome; the median AOFAS score was 95.0 (range 45–100). No signs of degenerative changes were seen in both groups at follow-up.

Conclusions

Fixation and debridement and bone marrow stimulation of an osteochondral talar defect are both good surgical options after failed conservative treatment.

Level of evidence

Retrospective case series, Therapeutic, Level IV.     

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.     

Comparison of clinical outcomes between arthroscopic subchondral drilling and microfracture for osteochondral lesions of the talus

Purpose

The objectives of this study were to compare the clinical outcomes of the two common bone marrow stimulation techniques such as subchondral drilling and microfracture for symptomatic osteochondral lesions of the talus and to evaluate prognostic factors affecting the outcomes.

Methods

Ninety patients (90 ankles) who underwent arthroscopic bone marrow stimulation for small- to mid-sized osteochondral lesions of the talus constituted the study cohort. The 90 ankles were divided into two groups: a drilling group (40 ankles) and a microfracture group (50 ankles). Each group was matched for age and gender, and both groups had characteristics similar to those obtained from pre-operative demographic data. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the ankle activity score (AAS) were used to compare clinical outcomes, during a mean follow-up period of 43 months.

Results

The median AOFAS scores were 66.0 points (51–80) in drilling group and 66.5 points (45–81) in microfracture group pre-operatively, and these improved to 89.4 points (77–100) and 90.1 points (69–100) at the final follow-up, respectively. The median VAS scores improved at the final follow-up compared with the pre-operative condition. The median AAS for the drilling group improved from 4.5 (1–6) pre-operatively to 6.0 (1–8) at the final follow-up, while those for the microfracture group improved from 3.0 (2–8) to 6.0 (3–9). No significant differences were observed between the two groups in terms of the AOFAS scores, VAS, and AAS.

Conclusions

The arthroscopic subchondral drilling and microfracture techniques that were used to stimulate bone marrow showed similar clinical outcomes. The results of this study suggest that both techniques are effective and reliable in treating small- to mid-sized osteochondral lesions of the talus, regardless of which of the two techniques is used.

Level of evidence

Level III, retrospective comparative study.

     

Treatment of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection

Purpose

The aim of this study is to report the outcomes of the treatment of talar osteochondral lesions with arthroscopic microfracture technique and postoperative intra-articular hyaluronan injection.

Method

Fifty-seven patients (29 men, 28 women) with osteochondral lesions of the talus were included in this prospective randomized clinical study between the years 2003 and 2009. The patients were treated with arthroscopic debridement and microfracture technique. Randomly selected 41 patients were injected intra-articular hyaluronan (injection group). The remaining 16 patients did not receive postoperative injection (non-injection group). Assessment of the pain and functional outcomes was performed using the Freiburg and AOFAS ankle/hindfoot scoring systems.

Results

In the injection group, the mean postoperative Freiburg functional and pain scores were significantly higher compared to preoperative functional and pain scores (P < 0.001). Similarly, for the patients in non-injection group, the mean postoperative Freiburg functional and pain scores were significantly higher compared to preoperative functional and pain scores (P < 0.001). The AOFAS functional and pain scores of the patients in the injection group were significantly higher (P < 0.001) postoperatively compared to preoperative scores. Scoring the patients in the non-injection group according to AOFAS system also revealed significantly higher (P < 0.001) postoperative functional and pain scores over preoperative scores. The increase in the postoperative scores was found to be significantly higher in the injection group compared to non-injection group in both Freiburg and AOFAS systems (P < 0.001).

Conclusion

Treatment of osteochondral lesions of the talus using microfracture technique significantly improved functional and pain scores postoperatively. Additional treatment with intra-articular hyaluronan injection as an adjunct to microfracture technique may offer better clinical outcomes over microfracture technique alone.

Level of evidence

Randomized, controlled trial, Level I.     

Adhesion and collagen production of human tenocytes seeded on degradable poly(urethane urea)

Purpose

The aim of this study was to investigate whether human tenocytes taken from ruptured quadriceps tendon could be seeded on a biodegradable polycaprolactone-based polyurethanes (PU) urea scaffold. Scaffold colonization and collagen production after different culture periods were analyzed to understand whether tenocytes from ruptured tendons are able to colonize these biodegradable scaffolds.

Methods

Human primary tenocyte cultures of ruptured quadriceps tendons were seeded on PU scaffolds. After 3, 10 and 15 days of incubation, the samples were stained with haematoxylin and eosin and were examined under white light microscopy. After 15 and 30 days of incubation, samples were examined under transmission electron microscope. Total collagen accumulation was also evaluated after 15, 30 and 45 days of culture.

Results

After 15 and 30 days of culture, tenocyte-seeded scaffolds showed cell colonization and cell accumulation around interconnecting micropores. Tenocyte phenotype was variable. Collagen accumulation in seeded scaffolds demonstrated a progressive increase after 15, 30 and 45 days of culture, while control non-seeded scaffolds show no collagen accumulation.

Conclusion

These results showed that human tenocytes from ruptured quadriceps tendon can be seeded on polycaprolactone-based PU urea scaffolds and cultured for a long time period (45 days). This study also showed that human tenocytes from ruptured tendons seeded on PU scaffolds are able to penetrate the scaffold showing a progressively higher collagen accumulation after 15, 30 and 45 days of incubation. This study provides the basis to use this PU biodegradable scaffold in vivo as an augmentation for chronic tendon ruptures and in vitro as a scaffold for tissue engineering construct.     

Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms

Introduction

Coiling is the gold standard for the treatment of intracranial aneurysms. However, some issues associated with endovascular treatment limit its long-term efficiency. Recanalization with coil compaction is certainly the most important. New approaches may be considered to promote thrombus colonization by mesenchymal cells and aneurysm healing. In the present study, we have percutaneously delivered autologous bone marrow mesenchymal stem cells (BMSCs) to an elastase-induced rabbit carotid aneurysm model in vivo.

Methods

Autologous mesenchymatous stem cells were obtained after femoral puncture and bone marrow aspiration. After 2 weeks of in vitro cell culture, five million BMSCs were grafted in the carotid aneurysm using an endovascular approach.

Results

We demonstrated the feasibility of in vivo percutaneous seeding of autologous BMSCs in the aneurysm by positive Hoechst fluorostaining. Two weeks later, conventional angiography showed an increase in median aneurysmal surface in the sham group, whereas this surface was decreased in the group treated with BMSCs, +28.4 versus ?26.4 %, respectively (p?=?0.01). BMSC seeding resulted in intimal hyperplasia with cell colonization and disappearance of the thrombus.

Conclusion

In conclusion, percutaneous seeding of BMSCs may colonize and heal the arterial wall thus limiting aneurysm expansion.     

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.     

Treatment of post-traumatic osteochondral lesions of the talus: a four-step approach

Purpose

The purpose of this retrospective study was to assess the treatment of post-traumatic osteochondral lesions (OCLs) of the ankle with a four-step protocol.

Methods

Thirty-eight patients with at least one MRI-documented OCL of the ankle were treated from 2004 to 2010. Median age at surgery was 39 years (range: 18–52). Mean lesion size was 1.0 cm² (SD: 0.2). All patients underwent a four-step surgical procedure including synovectomy, debridement and microfractures of the OCL, capsular shrinkage, and bracing and non-weightbearing for 21 days. Clinical assessment included objective examination, the AOFAS ankle and hindfoot scoring system, Karlsson-Peterson score, Tegner activity level, and Sefton articular stability scale. MRI scans were taken 18 months after surgery in all patients.

Results

Follow-up examination at an average of 4 years (SD: 1.1) after surgery showed significant improvement of all variables compared to pre-operative values (P < 0.05). Most patients rated their outcome as good/excellent. MRI scans taken 18 months after surgery documented completely repaired lesion in 27 ankles, slight bone marrow oedema with partially repaired defect in 9 patients, and visible defect in 2 ankles.

Conclusion

Based on the present results, we propose a comprehensive four-step protocol as a safe and clinically effective treatment option in patients with post-traumatic OCLs of the ankle.

Level of evidence

Retrospective case series, Level IV.     

Indications and limitations of osteochondral autologous transplantation in osteochondritis dissecans of the talus

Purpose

Osteochondral autologous transplantation (OAT) from the ipsilateral femoral lateral condyle in osteochondritis dissecans (OD) of the talus has shown good clinical results in the past. To further define, indications and limitations of OAT various factors have been discussed which might influence the clinical outcome.

Methods

In this study, the clinical outcome of OAT of 32 patients (mean follow-up 29 months) was evaluated by means of the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, ankle pain on the visual analogue scale (VAS), and Hospital for Special Surgery (HSS) Patella score. We then analysed the statistical correlation between clinical outcome and various variables such as age, pre-existing osteoarthritis, or size of the lesion.

Results

Median AOFAS score was 86 (range 68–100), median ankle pain on VAS was 2.0 (range 0–5.5), and median HSS Patella score was 95 (range 35–100). Advanced age (above 40 years of age) was associated with a significantly lower HSS Patella score (80 vs. 97.5, p = 0.035). None of the other variables (obesity, pre-existing osteoarthritis, size of the lesion, necessity of malleolar osteotomy, localization of the lesion, and number of previous surgeries) influenced the clinical outcome adversely.

Conclusions

Osteochondral autologous transplantation in OD of the talus is a safe procedure with good clinical results. As advanced age is associated with higher donor-site morbidity, indication for OAT in older patients should be carefully considered. As none of the other variables affected the clinical outcome of OAT adversely, there is no contraindication for OAT, for example, in osteochondral lesions requiring more than one osteochondral grafts, lateral lesions, patients with BMI >25, pre-existing osteoarthritis, or failed previous surgery.

Level of evidence

IV.     

Critical three-dimensional factors affecting outcome in osteochondral lesion of the talus

Purpose

This study aimed to investigate the relationship between clinical outcomes, patient demographics and the 3D-geometric profiles of the osteochondral lesion of the talus (OLT) following arthroscopic debridement and bone marrow stimulation.

Methods

Between 2005 and 2011, arthroscopic debridement and bone marrow stimulation were performed on 50 ankles with OLT mean age of 36.0 (19.1) years and mean follow-up time of 35.5 (20.2) months. Clinical data were assessed using validated Japanese Society of Surgery of the Foot scoring. An outcome was deemed unsatisfactory if the JSSF score was less than 80. Magnetic resonance imaging and X-rays were used to assess the 3D-geometric profiles of the OLT.

Results

The mean preoperative and postoperative scores were 73.4 (13.6) and 89.6 (11.5), respectively (p < 0.001). Unsatisfactory outcomes were identified in 12 % of patients. Linear regression analyses showed that lesion depth and patient age were significantly negatively correlated with postoperative scores (p < 0.001). High prognostic significances were attributed to defect depth and age of patient, and cut-off values of 7.8 mm and 80 years, respectively, were recommended to avoid a postoperative score less than 80. No significant correlations between poor clinical outcome and the other lesion profiles or demographic factors were identified.

Conclusion

Using 3D-geometric and demographic profiles, defect depth and age of patient are essential prognostic factors in OLT and may act as a basis for preoperative surgical decisions. A lesion depth ≥7.8 mm and age ≥80 years predict an unsatisfactory outcome following arthroscopic debridement and bone marrow stimulation.

Level of evidence

Retrospective comparative study, Level III.     

Is there a role for adult non-cultivated bone marrow stem cells in ACL reconstruction?

Purpose

To assess by magnetic resonance imaging (MRI) if adult non-cultivated bone marrow stem cells accelerate tendon-to-bone healing in the femoral tunnel, after hamstring anterior cruciate ligament (ACL) reconstruction.

Methods

Forty-three patients underwent ACL reconstruction and were prospectively randomized into two groups: 20 patients in the experimental group (group A) with adult non-cultivated bone marrow stem cells and 23 patients in the control group (group B) without adult non-cultivated bone marrow stem cells. All patients underwent MRI of the knee at three months after surgery to evaluate the signal-to-noise ratio of the interzone.

Results

There was no difference in the signal-to-noise ratio of the interzone on MRI between the experimental and the control group.

Conclusions

Adult non-cultivated bone marrow stem cells do not seem to accelerate graft-to-bone healing in ACL reconstruction. The clinical relevance of this finding is that adult non-cultivated bone marrow stem cells apparently have a limited role in ACL reconstruction.

Level of evidence

II.     

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years

Purpose

The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen–hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions.

Methods

In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness.

Results

A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups.

Conclusions

This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions.

Level of evidence

I.

     

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.     

Arthroscopic autologous chondrocyte implantation in the ankle joint

Purpose

Autologous chondrocyte implantation (ACI) is an established procedure in the ankle providing satisfactory results. The development of a completely arthroscopic ACI procedure in the ankle joint made the technique easier and reduced the morbidity. The purpose of this investigation was to report the clinical results of a series of patients who underwent arthroscopic ACI of the talus at a mean of 7 ± 1.2-year follow-up.

Methods

Forty-six patients (mean age 31.4 ± 7.6) affected by osteochondral lesions of the talar dome (OLT) received arthroscopic ACI between 2001 and 2006. Patients were clinically evaluated using AOFAS score pre-operatively and at 12, 36 months and at final follow-up of 87.2 ± 14.5 months.

Results

The mean pre-operative AOFAS score was 57.2 ± 14.3. At the 12-month follow-up, the mean AOFAS score was 86.8 ± 13.4 (p = 0.0005); at 36 months after surgery, the mean score was 89.5 ± 13.4 (p = 0.0005); whereas at final follow-up of 87.2 ± 14.5 months it was 92.0 ± 11.2 (p = 0.0005). There were three failures. Histological and immunohistochemical evaluations of specimens harvested from failed implants generally showed several aspects of a fibro-cartilaginous tissue associated with some aspects of cartilage tissue remodelling as indicated by the presence of type II collagen expression.

Conclusion

This study confirmed the ability of arthroscopic ACI to repair osteochondral lesions in the ankle joint with satisfactory clinical results after mid-term follow-up.

Level of evidence

IV, retrospective case series.     

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.     

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.     

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.