Intracranial aneurysm is a crucial disease that tremendously burdens families and health systems. Despite geographical locations or ethnicity, the non-comorbidity overall prevalence of unruptured intracranial aneurysms (UIAs) is approximatively 3-5% in the population [69]. UIAs are more prevalent in women than in men and there are no differences in age, expect for the under 30 years patients [69]. Once intracranial aneurysms rupture, subarachnoid hemorrhage often occurs in the brain. According to a recent prospective observational study [56], based on current treatment guidelines, patients with aneurysmal subarachnoid hemorrhage have a 5-year mortality of 29%, and just 64% of these patients were alive without disabilities at a 5-years follow-up. Nevertheless, with the development of medical techniques, the case fatality of aneurysmal subarachnoid hemorrhage has been declining. According to a meta-analysis of 33 articles, case fatality has decreased by around 23% between 1972 to 2003 [45].

There are two types of treatment: neurosurgical treatment and endovascular treatment (EVT) (Fig. 1). Surgical clipping was once considered as the gold standard; however, with the appearance and prevalence of alternative endovascular treatment, the status of surgical clipping is challenged. Nevertheless, surgical clipping is still a safe and effective method to treat aneurysms. Endovascular treatment also has many disadvantages, such as recanalization, bleeding during the operation. Especially in the treatment of complex intracranial aneurysms, endovascular therapy has many limitations. In postoperative patients with UIAs, its mortality is around 1-3%, and its rate of unfavorable outcomes (including death) is around 7% [30] and some claim that in low-risk cases, microsurgical treatment is a preferential choice [29].

In 1990, the first endovascular device appeared in clinical practices [20] and it is gradually becoming prevalent compared with neurosurgical treatment [7,34]. A meta-analysis [44], including 5,044 patients with UIAs from 71 studies, showed that EVT-associated mortality is around 2%, and the rate of unfavorable outcomes (including death) is around 4.8%.

Since the introduction of this new method in clinical use, many studies compared neurosurgical and endovascular treatments. In the field of aneurysms’ rupture, the International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling started as early as 1994 [38,40]. The ISAT randomly assigned 2143 patients with ruptured intracranial aneurysms to neurosurgical clipping (n=1070) or endovascular coiling (n=1073). Two months after treatments, 26.1% of patients who were allocated to EVT and 36.9% of patients who were allocated to neurosurgery were known to be dead or dependent (relative risk=0.71). One year after treatments, 23.5% of patients who were allocated to EVT and 30.9% of patients who were allocated to neurosurgery were known to be dead or dependent (relative risk=0.76). Among the patients who were allocated to EVT or neurosurgery, case fatality rates in the first years were around 8% and 10%, respectively. Furthermore, it seems that there were more likely deaths allocated to neurosurgery than EVT within the first seven years. Both risks of late rebleeding are low, though the risk is more common after EVT. In 2015, a follow-up article [39] of the ISAT concluded that the ten years’ possibility of disability-free survival was significantly higher in the EVT group compared with that in the neurosurgical group. In 2013, a meta-analysis on ruptured intracranial aneurysms [32] that included 11,568 patients from 27 studies, concluded that EVT generates a better clinical outcome than neurosurgical treatment, and that EVT leads to a higher risk of rebleeding. In 2018, a systematic review on aneurysmal subarachnoid hemorrhage [33] that included 2,458 patients from 4 randomized controlled trials, concluded that if the aneurysm is suitable for both EVT and neurosurgical clipping, EVT is associated with a better outcome. In the field of UIAs, some studies were carried out simultaneously and a recent meta-analysis [1] that included 106,433 patients from 144 studies about UIAs, concluded that among patients allocated to EVT or neurosurgery, the risks of procedural clinical complications (including death) were 4.96% and 8.34%, respectively. However, the case-fatality rates of both were similar (0.3% and 0.1%, respectively).

It seems that EVT is the best choice for patients with UIAs or ruptured aneurysms; however, it is still a complicated procedure for clinical strategy, especially for patients with UIAs who face the decision of whether to choose conservative management or interventional treatment. Some studies suggested that most UIAs do not rupture [75]. Moreover, a study [2] sent questionnaires to patients with UIAs who received preventive treatments (including EVT and neurosurgical treatment) and found that some patients suffered a reduction in life satisfaction during the post-treatment recovery period. Approximatively 19% of the patients did not recover to preintervention functioning, and approximatively 22% of the patients who were employed before aneurysm treatments cannot work like before. However, risk factors for aneurysm rupture should be considered, especially independent risk factors, including age, hypertension, history of subarachnoid hemorrhage, aneurysm size and location, and geographical region [19]. Some risk factors for aneurysm rupture, such as smoking, a family history of intracranial aneurysms, genetic factors, aneurysm shape or morphology, and the direction of blood flow into the aneurysm, are also important [14]. Before EVT, factors associated with complications from EVT, female, diabetes, hyperlipidemia, cardiac comorbidity, wide aneurysm neck, posterior circulation aneurysm, stent-assisted coiling, and stenting, should be considered [1]. Meanwhile, patients’ thoughts and anxiety are worthy of consideration, and therefore, it is important to individualize treatments.

Traditional EVT is a procedure which involves putting coils into intracranial aneurysms. To achieve this procedure, operators use a catheter with a small diameter to deliver coils. When coils arrive at the aneurysms, they will be released and packed. In the first reported endovascular treatment, operators used electrolytically detachable coils, which are made of platinum and depend on the electrolytic detachment method [20]. Then with the development of EVT, more advanced materials, designs, and detachment methods appeared.

One of the most prevalent materials is platinum-based material. This marvel material performs well, overwhelming the use of other metal materials. Due to their chemical stability, platinum-based materials rarely corrode in physiological environments or cause allergic reactions. They can be made into 25 m size material, while also maintaining a similar mechanical strength. Furthermore, platinum can be clearly seen in X-ray images during an operation because of its radiopacity [78]. Unlike magnetic metals, platinum can be carried into magnetic resonance imaging (MRI) devices, which brings convenience to patients.

Regarding the structure, due to the fragility of the aneurysm wall, coils should be soft enough and decently increase the Intrasaccular pressure. Meanwhile, the structure should keep stiff facing the blood flow to prevent recanalization. Many coils are designed to improve embolism outcomes by promoting blood coagulation or increasing packing densities [78].

Electrolytic detachment has some drawbacks. For example, time spending is uncertain, and sometimes detachment needs several attempts to succeed. Moreover, gas generated from electrolysis may cause clot formation [78]; however, the appearance of hydraulic and mechanical detachments has solved these annoying problems.

The primary coil system, also known as Guglielmi detachable coil (GDC), is a typical coil. A study [66] that followed 141 aneurysms in 130 patients who were treated with GDC between January 1995 and August 1999 showed that occlusion rates after six months or longer were 100% for 61%, more than 95% for 22%, and less than 95% for 17%. Just one recurrence occurred on the 6-month follow-up angiogram. However, another study [52] that followed 501 aneurysms in 466 patients who were treated with GDC between August 1992 to May 2002 showed that the rate of complete occlusion after 12 months is 38.3%, and the rate of recurrences is 33.6%. In 2013, a meta-analysis [55] from 104 studies that included 22,134 aneurysms treated with bare coils, concluded that the overall unfavorable angiographic outcome rate was 17.8% (the unfavorable angiographic outcome is defined as any degree of recurrence).

Various materials, such as polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), nylon, or expandable hydrogel, have been applied to improve occlusion rates and avoid recurrence. These newer coils are called bioactive coils.

Nevertheless, the appearance of these named bioactive coils caused huge controversy due to their availability on the market without valid clinical trials [12,53]. A study that performed a systematic review of the literature from 2002 to 2007 reported the following statement regarding the products: “illustrates the failure of the industry, the regulatory authorities, and the neuro-interventional community combined to provide a reliable and prudent approach to the introduction of new devices” [74].

In 2008 and 2011, two reports [72,73] on a hydrogel coil trial indicated that hydrogel coils are safe and lower major recurrence, but whether they improve long-term clinical outcomes was not clear. In 2008, a trial [68] about Nexus coils (coils with PGLA microfilament threads) showed that PGLA has no effect on reducing recurrence. In 2013, a meta-analysis [54] from 82 studies between 1999 and 2011, claimed that coil type does not significantly affect angiographic follow-up outcomes. Besides, bioactive coils may induce headache and fever due to their inflammatory effects [63].

However, new bioactive coils have been evolving. In 2016, a meta-analysis [8] that included 2168 patients of 5 randomized clinical trials between 2011 and 2014, showed that bioactive coils have a high rate of a complete aneurysm occlusion and a reduced the rate of residual neck aneurysms in the mid-term when compared with bare coiling. Nevertheless, a recent 5-year follow-up randomized trial that included 580 patients compared the effectiveness of bioactive coils (Matrix2) to bare coils and showed that there is no significant difference between bioactive coils and bare coils [36].

While coil is prevalent among filling materials, it also has disadvantages. Volumetric ratio (coil/aneurysmal volume) is a crucial index that may determine the possibility of recanalization [64,67]. Although it is entirely possible to fill the aneurysm, the volumetric ratios of coils are less than 37% [49]. However, with the help of balloon-assisted or stent-assisted coiling, the risk of coil protrusion dramatically decreased. Nevertheless, it makes the procedure more time-consuming.

In 2006, an experimental endovascular treatment used a liquid material called thermoreversible gelation polymer and succeeded [62]. Then, other hydrogel embolic materials proved their effectiveness in vitro [3,4,50,51]. No clinical trial has assessed the practicability of hydrogel materials, though hydrogel material is considered a promising material [27].

In 2015, a study assessed two new devices, called the coil-in-shell and the gel-in-shell, in porcine sidewall aneurysms [37]. The devices comprise coils or hydrogel surrounded by a shell composed of hyaluronic acid and polyurethane copolymer. They performed well in minimizing aneurysm recurrence. This study suggested that coil-in-shell or gel-in-shell depends on the stimulation of tissue coverage at the neck rather than a complete initial occlusion which can eventually facilitate aneurysm occlusion and neointimal healing.