Cranioplasty is required to restore the appearance of the skull, protect intracranial tissue, and improve neurological function^1,2). Autologous bone flaps are usually the first choice at most institutions, as they are readily available at no additional cost and yield excellent outcomes^3,4).

Although autologous bone remains the first choice for repair, it is not always used because of infection, fragmentation, bone resorption, or other causes^5,6), which has led to the use of synthetic alternatives⁷⁾. The ideal cranioplasty material is nonmagnetic, radiolucent, light, sterilizable, and easily affixed to the skull. Currently, the three most popular nonbiological materials used for this purpose are polymethylmethacrylate (PMMA), hydroxyapatite, and titanium meshes or plates. However, trials using materials such as polyether ether ketone and porous polyethylene are also being conducted⁸⁾.The procedures for using these materials vary between centers, with some preferring to shape the implant intraoperatively, while others choose to create custom-made plates preoperatively using computed tomography (CT) or stereolithography data^8,9,10).

Three-dimensional (3D) printing techniques are evolving, and their application in medical technology, such as utilizing it to make artificial bone flaps for various surgeries is increasing,^11,12). This study aimed to analyze the outcomes of using a customized artificial skull bone flap made by a 3D printing technique for cranioplasty, compared with autobone. Significant results were confirmed as statistical differences between the results of cases.

This study was a retrospective study of medical records, including a survey of satisfaction after 3D cranioplasty (3DC). All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethical Committee of Busan Paik Hospital of Inje Medical University and with the Helsinki Declaration. Since this study was conducted retrospectively, it was exempted from that criterion.

Forty patients were included in this study (average age, 51.1 years; 21 male). 3DC was performed in 24 patients (average age, 49.5 years; 16 male) and autobone cranioplasty (AC) was performed in 19 patients (average age 49.7 years; 8 male). Among them, 26 patients had cerebrovascular accidents (cerebral infarction, aneurysmal spontaneous subarachnoid hemorrhage, spontaneous intracranial hemorrhage (ICH), one brain abscess, and 13 head traumas. The mean interval between craniectomy and cranioplasty was 5.6 months (3DC group, 6.6 months; AC group, 4.3 months; p=0.123). The affected hemispheres were 27 on the right and 17 on the left (p=0.096; in one case, AC for both frontal craniectomies were performed in one step. The average operation time was 167.3 min (3DC group, 168.5 min; AC group, 165.8 min; p=0.889). The average blood loss during operations was 172 mL (3DC group, 184 mL; AC group, 156 156 mL; p=0456). Cranioplasty-related complications occurred in eight cases (3DC group, two; AC group, six; p=0.061). There were no statistically significant differences in age, sex, interval between craniectomy and cranioplasty, operation time, and blood loss between the two groups. In four patients in the AC group, cranioplasty was accompanied by bone cement. (Table 1)

The average of circumference of craniectomy was 403 mm (3DC group, 399 mm; AC group, 408 mm; p=0.730) and surface area of skull defect was 103.93 cm² (3DC, 106.74 cm²; AC, 100.39 cm²; p=0.503). The average bone flap circumference was 363 mm. (3DC, 366 mm; AC, 359 mm; p=0.687), and average of surface area of the bone flap was 98.95 cm² (3DC, 105 cm², AC, 90 cm²; p=0.112). However, bone flap coverage of the skull defect was 95.2% (3DC, 98.6%, AC, 90.9%; p=0.000), and the area of defect was 498 mm² (3DC, 146 mm², AC, 943 mm²; P-value 0.000). In addition, the average size of defect was 1.23 mm (3DC, 0.35 mm, AC, 2.35 mm; p=0.000). In this data, bone flap coverage, area of defect, and average of defect showed statistically significant differences (p< 0.000), and are summarized in Table 2. Supplementary Fig. 1 shows the high skull defect coverage of the 3DC.

In the case of cranioplasty-related complications, there were two operation-related complications (one case of cosmetic issues and one case of ICH after cranioplasty) in the 3DC group, and six (one episode of extradural hematoma after cranioplasty, one case of cosmetic issue, two cases of bone floating, and two cases of infection requiring bone-flap removal) in the AC group. (p=0.061) Table 3 summarizes the data. Temporal muscle atrophy was inevitable even with 3DC. (Supplementary Fig. 2) Regarding AC, bone flap floating occurred in two cases. (Fig. 3)

In the 3DC group, the preoperative modified Rankin Scale (mRS) scores were as follows: (4 points, 6 patients; 5 points, 6 patients). The postoperative scores were as follows: (4 points, 7 patients; 5 points, 0 patients). In addition, preoperative mRS scores of the AC group were as follows: (4 points, 5 patients; 5 points, 1 patient). The postoperative scores were as follows: (4 point, 3 patients; 5 point, 0 patients). There was no patient with a lowering of mRS after the operation in any group, and the clinical course was confirmed to have improved. (Table 4)

A large format (i.e., > 25 cm²) cranioplasty is a challenging procedure not only from a cosmetic standpoint, but also in terms of ensuring that the patient's brain is well protected from direct trauma, sinking flap syndrome, and syndrome of the trephined. Until recently, when a patient's cranial flap was unavailable, it was difficult to achieve these goals. It is now possible to 3-D-print patient-specific implants from a variety of polymer, ceramic, or metal components. A 3D printing design may be used to imitate the previous external shape of the skull that will become well integrated into the skull while providing beneficial distribution of mechanical force in the event of trauma¹³⁾. Recently, 3D printing flaps have been increasingly used in patients undergoing cranioplasty^14,15).

If 3D printing flaps are used, there would be advantages in the infection ratio and cosmetic area¹⁶⁾. In this study, we evaluated and compared the defects between the autobone flap and 3D printing flap for cosmetic points. In general, craniectomy is focused on the temporal area to achieve maximal decompression. With the increase in subtemporal decompression, the prognosis of the patient would improve if the shape of the midbrain is restored and the cerebrospinal fluid flow is smooth¹⁷⁾. However, the removed skull bone can remain as temporal bone defects that are not well covered in AC. In the case of the 3D printing flaps, the temporal defect can be solved by imitating the unaffected skull.

There are multiple holes in the 3D printing flap. Using these multiple holes, sufficient dural tenting can be performed to reduce additional manipulation. When using an autobone, a suture hole for tenting must be made using a drill, hand manipulation is involved, and the number of holes is limited. In a 3D printing flap, dural tenting can be performed more easily because of multiple holes. However, epidural fluid collection occurred in both groups in this study. Such complications vary depending on the surgeon. There was a difference in the dissection of the adhesion site and epidural space control. To prevent epidural fluid collection, it is important to meticulously check the leakage point and perform duroplasty. In the case of autobone complications that were not seen in 3D printing cranioplasty, calcified deposits were found in the soft tissue. In the case of AC, cement is used as a complementary method for the defect. Forming cement for cranioplasty can increase the infection risk by using hand manipulation and develop complications in which a fragment of cement is found in soft tissue, as in the case of a patient in this study.

Additional treatment caused by a cranioplasty defect may increase the risk of infection due to an increase in operation time and hand manipulation. However, in the case of 3DC, all defects were designed to be covered, and this might have been better than the autobone flap in this regard. Postoperative infection was not observed in the 3DC group. If an infection develops after AC, it is impossible to reuse the autobone because it may provide bacterial culture. Conversely, a 3D printing flap is formed using titanium, which has a lower infection rate. In cases of infection caused by using an autologous skull bone flap, the infection must be overcome through revision surgery using a 3D printed bone flap. In addition, resorption may occur due to apoptosis of the bone flap in the AC¹⁸⁾. In such cases, the defect at the cranioplasty site could increase, resulting in a decrease in bone density¹⁹⁾.

There was no statistical difference in the operation time and blood loss between the AC and 3DC groups. In all patient groups, operation time and blood loss were required during adhesiolysis of the dura mater from the scalp. In the case of 3D printing flap cranioplasty, multiple holes can be tented with the screw fixation site, and the procedure required during operation has been shortened. In terms of patient satisfaction, all the patients were generally satisfied. In the case of a 3D printing flap, additional manufacturing is possible according to the patient. As it is manufactured based on muscle atrophy and according to the opposite side of the skull, it can be customized to a shape that suits the skull defect. However, in 3D bone flaps, a 1 mm thin-cut CT examination must be additionally performed for preoperative production, and it has the disadvantages of extra cost and radiation exposure risk.

In this study, we evaluated cranioplasty using a 3D printed bone flap and an autobone flap. The 3DC group had a high skull defect coverage rate and a low complication rate.

This was a retrospective medical record study with few cases. However, many artificial materials made by 3D printing techniques are currently used in surgery, and we expect this technique to develop rapidly. Therefore, future studies are essential to 3D-printing medical materials.

Cranioplasty using a customized artificial bone flap made by a 3D printing technique was effective for covering skull defects with lower complication rates than the autobone technique.