The aim of this study is to report a protocol for the arthroscopic treatment of osteochondral lesions of the talus using microfractured and purified adipose-derived stem cells.
In recent years, regenerative techniques have been increasingly studied and used to treat osteochondral lesions of the talus. In particular, several studies have focused their attention on mesenchymal stem cells derived from adipose tissue. Adipose-derived stem cells (ADSCs) exhibit morphological characteristics and properties similar to other mesenchymal cells, and are able to differentiate into several cellular lines. Moreover, these cells are also widely available in the subcutaneous tissue, representing 10 – 30% of the normal body weight, with a concentration of 5,000 cells per gram of tissue.
In the presented technique, the first step involves harvesting ADSCs from the abdomen and a process of microfracture and purification; next, the surgical procedure is performed entirely arthroscopically, with less soft tissue dissection, better joint visualization, and a faster recovery compared with standard open procedures. Arthroscopy is characterized by a first phase in which the lesion is identified, isolated, and prepared with microperforations; the second step, performed dry, involves injection of adipose tissue at the level of the lesion.
Between January 2016 and September 2016, four patients underwent arthroscopic treatment of osteochondral lesion of the talus with microfractured and purified adipose tissue. All patients reported clinical improvement six months after surgery with no reported complications. Functional scores at the latest follow-up are encouraging and confirm that the technique provides reliable pain relief and improvements in patients with osteochondral lesion of the talus.
Arthroscopy is the gold standard for the treatment of osteochondral lesions of the talus (OLTs) with the aim of pain relief, restoring functionality, and improving quality of life, especially in young and active patients.
Currently, arthroscopic techniques can be classified in three ways. The reparative technique stimulates cells derived from bone marrow through a debridement and microperforations at the level of lesion. The reconstructive technique replaces the lesion using an autologous or heterologous ostechondral graft. The regenerative technique exploits the ability of multipotent cells to differentiate and replicate to reconstruct the damaged tissue1,2,3,4,5,6.
In recent years , regenerative techniques have been the subject of numerous in vitro and in vivo studies for the treatment of OLTs, and particularly mesenchymal stem cells derived from adipose tissue (ADSCs)7,8,9. These mesenchymal stem cells exhibit morphological and functional characteristics similar to other multipotent cells, isolated from other tissues; they also have the ability to differentiate into several and different cellular lines both in vitro and in vivo10,11,12,13. The focus on research regarding these cells is mainly due to their localization, in fact they represent from 10% to 30% of normal body weight with a concentration of 5,000 cells per gram of tissue13,14. On the other hand, a factor that limits the use of these cells is related to their handling during laboratory procedures. The lipoaspirate containing aggregates of adipocytes, collagen fibers, and normal vascular components is enzymatically processed with collagen A type I, and subjected to hemolysis before culture. The aim here is to describe the protocol for the treatment of osteochondral lesions of the talus using microfractured and purified adipose tissue.
All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
1. Medical History
2. Clinical Examination
3. Radiological Assessment
4. Surgical Technique
5. Postoperative Care
6. Clinical and Radiographic Follow-Up
Between January 2016 and September 2016, four patients underwent arthroscopic treatment of osteochondral lesion of the talus with microfractured and purified adipose tissue. All patients reported clinical improvement six months after surgery. Preliminary clinical results are reported in Table 1. No complications were reported.
In recent years, the use of ADSCs for the treatment of foot and ankle pathologies has increased. In 2013, Kim et al.23 treated 65 elderly patients, older than 50 years for symptomatic OLT dividing for the type of treatment:
– isolated marrow stimulation
– marrow stimulation in association with ADSCs
At final follow-up, patients with a combined treatment showed significant clinical improvement compared to the isolated marrow stimulation treatment. A subsequent study, conducted by the same group24, for the treatment of OLT, confirmed how the combined treatment of SVF and marrow stimulation was superior to isolated microfracture.
In 2016, Kim et al.25 assessed the outcomes in 49 patients treated with marrow stimulation and lateral sliding calcaneal osteotomy. Twenty-six patients also underwent MSC injection. One year after surgery, patients treated with MSC reported a higher ICRS score and clinical outcomes. Recently, Kim et al.26 noted that patients treated with MSC injection after supramalleolar osteotomy and marrow stimulation reported higher clinical and radiological outcomes, compared to patients treated without MSC.
Figure 1: Saline solution containing adrenaline and lidocaine is injected at the level of the abdomen using a 20 g cannula. For liposuction, use a 13 g cannula connected to a syringe. Please click here to view a larger version of this figure.
Figure 2: The processing kit for fat tissue consists of a single-use kit for the lipoaspiration and purification of adipose tissue. All procedures are performed with the ADSCs immersed in a saline solution, avoiding any trauma and maintaining intact the vasculostromal niches containing mesenchymal stem cells and pericytes. The unit consists of a transparent plastic cylinder with filters and beads for the microfracturing of adipose tissue. Please click here to view a larger version of this figure.
Figure 3: Outside views of ankle during surgical planning. With the patient in the supine position, it is useful to identify all the landmarks on the joint needed for the surgical procedure.
AM = anteromedial portal
AL = anterolateral portal
MM = medial malleolus
LM = lateral malleolus
TAT = tibalis anterior tendon
JL = joint line
SPN = superficial peroneal nerve Please click here to view a larger version of this figure.
Figure 4: Arthroscopic view. The lesion is prepared using a curette removing the damaged cartilage and the necrotic and sclerotic bone Please click here to view a larger version of this figure.
Figure 5: Arthroscopic view. Microfractures, performed at the level of the osteochondral lesion, stimulate bleeding and leakage of mesenchymal stem cells from the subchondral bone. Please click here to view a larger version of this figure.
Patients | Pre-operative | 6 months after surgery | ||||
AOFAS | VAS | SF-12 | AOFAS | VAS | ||
PCS | MCS | |||||
1 | 44 | 8 | 31.1 | 32.4 | 88 | 3 |
2 | 32 | 7 | 27.5 | 42.1 | 78 | 2 |
3 | 52 | 9 | 40.1 | 28.7 | 87 | 2 |
4 | 59 | 8 | 36.6 | 41 | 82 | 2 |
Mean | 46.75 | 8 | 33.83 | 36.05 | 83.75 | 2.25 |
Table 1: Clinical results at 6 months of follow-up. AOFAS: The American Orthopaedic Foot and Ankle Society Score; VAS: Visual Analogue Scale for Pain; SF-12: 12-Item Short Form Survey; MCS: Mental Component Score; PCS: Physical Component Score.
In recent years, clinical and preclinical trials have focused their attention on the effect of ADSCs to treat different musculoskeletal pathologies. The aim of this article is to describe the protocol for the treatment of osteochondral lesions of the talus using microfractured and purified adipose tissue in association with arthroscopic microperforations. The protocol involves several critical steps with high risks of complications. During fat harvesting, complications can be divided into local or systemic complications.
The most common postoperative complication is contour irregularities, with an incidence of 2.7%. This can be avoided using small cannulas, not performing superficial liposuction, and turning the suction off when exiting incisions. Rarely, skin conditions such as hyperpigmentation, necrosis, and erythema in patients with underlying connective tissue disease can be seen27,28. Seromas are often the result of aggressive liposuction due to the collection of serous fluid in a treated area leading to the formation of a single cavity; this is most common in patients with high BMI29. Infection is a very rare complication (<1%) and this may be because of a combination of sterile technique, small incisions, and the antibacterial effects of lidocaine30.
The literature reports subsequent life-threatening complications after liposuction, such as pulmonary embolism, fat embolism, sepsis, necrotizing fasciitis, and perforation of abdominal organs. The most common cause of death is pulmonary thromboembolism. These complications are due to lack of sterility, poor patient compliance, and permissive post-operative discharge30.
Also during arthroscopy, there are critical steps that can lead to complications: in this protocol, all arthroscopic procedures are performed using an anteromedial and anterolateral portal31. The most frequent complication with this approach is a deficit of the superficial peroneal nerve, reported in 1.04% of patients, despite preoperative marking of the nerve and its branches32,33. Furthermore, the risk increases considering variations of this nerve: anatomical studies have demonstrated that 50% of the population present two branches, and these can reach up to 5 branches with an extremely variable width (1 to 13 mm).
The technique described in the protocol combines the effect of the microfracture in association with mesenchymal stem cells harvested from fat tissue. Microperforations stimulate the development of a reparative tissue: drilling the subchondral bone produces bleeding and leakage of mesenchymal cells, to produce fibrocartilage. The success of microfractures is strictly related to the size of the lesion. If lesions are less than 1.5 cm2, the neo-formed fibrocartilage tissue, although qualitatively different from hyaline cartilage and with lower mechanical properties, can provide adequate reparation, with resolution of the symptoms in a high percentage of cases34,35. ADSCs may form neo-tissue with a hyaline cartilage phenotype, if cultured in association with different growth factors (TGFb, GH, and FGF-2) and placed in a scaffold of fibrin glue36.
The described technique preserves the identity of the pericyte, leaving intact the stromal vascular niche, promoting osteochondral healing in this way. Moreover, ADSCs produce a variety of paracrine bioactive molecules and can activate the physiological healing process. The final product is available in less than 20 min, thanks to the gentle mechanical method. Finally, in accordance with the US Food and Drug Administration, ADSCs are minimally manipulated.
The use of MSCs is constantly increasing, and future research should focus on the use of allogeneic ADSCs as described by Lee37. The advantages of an allotransplant would be numerous. First of all, handling and standardization of the product would be easier. Liposuction and processing steps could be eliminated, and a healthy donor could be pre-selected, according to his cytokine and cell marker expression profile, improving the effect of MSCs38.
The authors have nothing to disclose.
The procedures are performed using the Lipogems System.
PROCESS KIT – PROCESSING KIT FOR FAT TISSUE | LIPOGEMS | LG PK 60 | Lipogems Kit to obtain microfractured and purified ADSCs |
HINTERMANN SPREADER | INTEGRA | 119654 | The spreader allow to access most of the talar dome, in particular in case of posterior lesion |
CUP CURETTE | ARTHREX | AR-8655-02 | To remove the damaged cartilage and necrotic and sclerotic bone |
CHONDRAL PICK 30° TIP / 60° TIP | ARTHREX | AR-8655-05 AR-8655-06 |
To perfrom microperforation at the level of the lesion, stimulating bleeding from the subchondral bone |
SHAVER | ARTHREX | AR-7300SR | To clean the joint and aspirate water |