The technique of microfracture (MFX) was first performed 40 years ago and served for many years as the main procedure for repairing cartilage defects. There is a need to improve microfractures because the regenerated cartilage differs from the original histological aspect; it is less hyaline and more fibrocartilaginous. In addition, and more importantly, the benefits do not persist and the long-term results are unsatisfactory.
Today, management strategies are oriented toward symptom control, so conservative treatment should serve as a first-line therapy. Different guidelines have recommended various non-operative treatments, such as exercise, weight control, acetaminophen, transcutaneous electrical nerve stimulation, oral NSAIDs, intra-articular injections, and other methods. The surgical procedure of replacing the joint is reserved for severely affected joints .
As a degenerative pathology, OA leads to irreparable cartilage lesions. Although joint replacement is an effective surgical intervention, in order to prevent the development of osteoarticular disease and avoid this major surgical procedure, other less invasive methods should be attempted, such as microfracture (MFX), alone or in combination with intra-articular injection of adipose-derived stem cells (ADSCs), bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), hyaluronic acid (HA), or cell-free scaffolds .
Cartilage lesions are a common issue and are present in more than 60% of knees on arthroscopy. About 5% are seen in younger patients under 40 years old. The management of cartilage lesions represents one of the most challenging problems for the orthopedic community. None of the existing techniques can fully restore the cartilage to its hyaline aspect .
The technique of microfracture was first performed 40 years ago and served for many years as a main procedure for repairing cartilage defects. The goal of this intervention is to provide the patient with both surgical and functional benefits. Throughout the years, the technique has constantly been improved by various researchers. There is a need to perfect MFX because the regenerated cartilage differs from the original histological aspect; it is less hyaline and more fibrocartilaginous. Moreover, the MFX procedure uses an awl to penetrate the bone, which leads to subchondral bone alterations such as cysts and a lower subchondral bone health score. These findings may affect clinical outcomes and may be responsible for the biological and mechanical impairment of the fibrocartilage repair tissue in the medium term and, possibly, the long term. Adjunctive treatments include platelet-rich plasma, hyaluronic acid, adipose-derived mesenchymal stem cells, and chitosan-based bioscaffolds ( Table 1 ) .
|Adjuvant MFX||Brief Definition|
|Mesenchymal stem cells||Characterized by the capacity to go through self-renewal and multi-lineage differentiation and create fully differentiated cells |
|Platelet-rich plasma||Autologous concentration of human thrombocytes in a small quantity of plasma |
|Hyaluronic acid||Natively occurring glycosaminoglycan with elasticity and viscosity properties that acts as a lubricating and shock absorbing liquid in joints |
|Chitosan-based scaffolds||Chitosan, the main constituent, is obtained from de-acetylation of chitin, the structural component of crustacean shells; it has reduced toxicity and good biocompatibility, adhesivity, and biodegradability |
|Collagen-based scaffolds||Collagen, the main constituent, is the most abundant protein in the extracellular matrix of many hard and soft tissues in the human body; the most important is type I collagen, which provides structural support to resident cells in both types of tissue |
The procedure starts with the creation of three portals around the knee; for the inflow cannula, the working instruments, and the arthroscope. First, an elaborate evaluation of the knee is carried out, including the suprapatellar pouch, patellofemoral joint, medial and lateral gutters, notch, and medial and lateral compartments. After visualization of the cartilage defect, the uncovered bone is debrided of any remaining cartilage tags by using a resector, and the intact cartilage around the defect is surgically prepared in order to form a pool where a clot can form. The calcified layer of cartilage that remains is delicately detached with a shaver. Caution must be taken not to harm the subchondral bone. Next, an arthroscopic awl is utilized to create a series of holes (microfractures) in the uncovered subchondral bone. The holes are about 3 to 4 mm apart and with a depth of 4 mm. This is the optimal distance that avoids the possible confluence of one hole into another. Typically, the microfractures are started from the periphery, moving to the center of the cartilage defect. After that, blood and droplets of fat from the holes can be observed .
The penetrated subchondral bone plate leads to the formation of a clot in the defect. This clot comprises pluripotent mesenchymal stem cells derived from the marrow, which will fabricate a fibrocartilage repair with varying quantities of type II collagen .
Although this is an inexpensive, easy, and popular technique, various studies have reported a series of limitations. The most important are that the benefits are not persistent, and the long-term results are unsatisfactory. Goyal et al. conducted a systematic review of 15 studies, and the overall results showed that microfracture has good results at short-term follow-up, but beyond 5 years postoperatively, failure can be expected, regardless of the size of the lesion. Oussedik et al. also performed a systematic review of bone marrow stimulation techniques, including MFX. They also found good early results, but noted that due to the abnormal new cartilage, unsatisfactory results can be expected in the long run, especially in larger defects .
Although microfracture is a safe and encouraging treatment for musculoskeletal diseases, evidence of its success has varied greatly and is very indication-specific. After setting the MFX holes, the arthroscopic liquid is cleared from the joint in order to create a dry environment for the application of the PRP mixture. The cubital veins can be used to collect 30 to 45 mL of whole blood into a 50 mL syringe that contains sodium citrate. The blood is anticoagulated and centrifuged at 1500 rpm for 10 min. After a second spin of 3000 rpm for 5 min, about 5 mL of PRP is obtained for each person. The PRP is infiltrated into the knee treated by MFX. This procedure can be repeated regularly, and patients follow a standard rehabilitation protocol .
PRP can be used to augment MFX due to the ability of platelets to liberate a series of growth factors that have an important role in building higher-quality cartilage. Arshi et al. included the effects of MFX + PRP in their systematic review. They obtained statistically significant improvements in postoperative IDKC and KOOS scores at 2 years. The newest meta-analysis dealing with the evaluation of PRP as an adjuvant for microfracture is by Boffa et al. (2020). They analyzed seven studies that met the inclusion criteria and suggested that PRP can improve the outcomes of MFX in knees and ankles at short-term follow-up. However, these ameliorations did not reach minimal clinically important differences (MCIDs), and thus they were not clinically perceivable by patients .
Recently, Yang et al. conducted a study on 79 patients, divided into a control group of 39 patients treated with MFX + PRP and an observation group of 40 treated by MFX alone. Parameters such as baseline data, pain level, knee range of motion, knee symptoms, motor function, knee function, and complications were evaluated. Significantly statistical results were obtained for IDKC scores ( p < 0.05) and for Tenger and Lysholm scores ( p < 0.05). The rate of complications was also better for the group treated with PRP as an adjuvant (10%, compared to 28% in the control group). Follow-up was done at 1, 2, and 3 months after surgery .
There are three basic elements in tissue engineering: cells, biodegradable scaffolds, and growth factors, which together provide a new method for the repair of articular cartilage. Scaffolds can provide a 3D structure for cartilage cells and favor cell adhesion and proliferation. They also mediate the signals and interactions between cells. The available literature offers various cell-free injectable scaffolds for treating cartilage lesions, such as HA-based, collagen-based, and chitosan-based .
Hyaluronic acid is a lubricant designed to reduce the pain and inflammation of articular surfaces and completes the endogenous joint fluid. Intra-articular injections are utilized for cartilage lesions and joint degeneration. HA has a high-molecular-weight glycosaminoglycan component, which is the reason for its viscoelastic attributes. Moreover, in order to provide joint lubrication and shock absorption, HA represents the main way for proteoglycans of the extracellular matrix to create a hydrated pathway through which cells can migrate .
HA as a scaffolding material depends largely on its bulk surface. The parameters that are used to describe the network structure of hydrogels include the molecular weight of the polymer chains, the corresponding mesh size, and the effective network density. HA-based scaffolds can bind to proteins and cells through cell surface receptors, such as CD44, RHAMM, and ICAM-1. HA scaffolds can bind to chondrocytes via CD44. Multiple biological processes mediated by these scaffolds are important for the wound healing process. This, coupled with the capacity to offer an open, hydrated structure for the passage of nutrients, makes them candidates for tissue regeneration and repair techniques .
Research has revealed that scaffolds made from dehydrated cartilage can stimulate adult stem cells to differentiate down a chondrogenic pathway, producing cells that show morphologic, molecular, and biochemical characteristics that resemble those of articular cartilage cells. The scaffolding allows for hyaline-like cartilage to regenerate within the defect, which enables better structural support for the defect and improved longevity of the repair .