Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients

Abstract

Three-dimensional (3D) printing offers the potential for rapid customization of medical devices. The advent of 3D-printable biomaterials has created the potential for device control in the fourth dimension: 3D-printed objects that exhibit a designed shape change under tissue growth and resorption conditions over time. Tracheobronchomalacia (TBM) is a condition of excessive collapse of the airways during respiration that can lead to life-threatening cardiopulmonary arrests. We demonstrate the successful application of 3D printing technology to produce a personalized medical device for treatment of TBM, designed to accommodate airway growth while preventing external compression over a predetermined time period before bioresorption. We implanted patient-specific 3D-printed external airway splints in three infants with severe TBM. At the time of publication, these infants no longer exhibited life-threatening airway disease and had demonstrated resolution of both pulmonary and extrapulmonary complications of their TBM. Long-term data show continued growth of the primary airways. This process has broad application for medical manufacturing of patient-specific 3D-printed devices that adjust to tissue growth through designed mechanical and degradation behaviors over time.

Fig. 1. Computational image-based design of 3D-printed tracheobronchial splints

(A) Stereolithography (.STL) representation (top) and virtual rendering (bottom) of the tracheobronchial splint demonstrating the bounded design parameters of the device. We used a fixed open angle of 90° to allow placement of the device over the airway. Inner diameter, length, wall thickness, and number and spacing of suture holes were adjusted according to patient anatomy (Table 1) and can be adjusted on the sub-millimeter scale. Bellow height and periodicity (ribbing) can be adjusted to allow additional flexion of the device in the z-axis. (B) Digital Image Communication in Medicine (DICOM) images of the patient’s CT scan were used to generate a 3D model of the patient’s airway via segmentation in Mimics. A centerline was fit within the affected segment of the airway, and measurements of airway hydraulic diameter and length were used as design parameters to generate the device design. (C) Design parameters were input into MATLAB to generate an output as a series of 2D .TIFF image slices using Fourier series representation. Light and gray areas indicate structural components; dark areas are voids. The top image demonstrates a device bellow and the bottom image demonstrates suture holes incorporated into the device design. The .TIFF images were imported into Mimics to generate an .STL of the final splint design. (D) Final 3D-printed PCL tracheobronchial splint used for used to treat the left bronchus of Patient 2. The splint incorporated a 90° spiral to the open angle of the device to accommodate concurrent use of a right bronchial splint and growth of the right bronchus. (E) Virtual assessment of fit of tracheobronchial splint over segmented primary airway model for all patients. (F) Mechanism of action of the tracheobronchial splint in treating tracheobronchial collapse in TBM. Solid arrows denote positive intra-thoracic pressure generated on expiration. Hollow arrow denotes vector of tracheobronchial collapse. Dashed arrow denotes vector of opening wedge displacement of the tracheobronchial splint with airway growth.

Fig. 2. Pre- and post-operative imaging of patients

Black arrrows in all figures denote location of the malcic segment of the airway. White arrows designate the location/presence of the tracheobronchial splint. All CT images are coronal Minimum intensity projection (MinIP) reformatted images of the lung and airway. All MRI images are axial proton density turbospin echo MRI images of the chest. (A) Pre-operative (top) and 1 month post-operative (middle) CT images of Patient 1. Post-operative MRI image (bottom) demonstrated presence of splint around left bronchus in Patient 1 at 12 months. (B) Pre-operative (top) and 1 month post-operative (middle) CT images of Patient 2. Post-operative MRI image (bottom) demonstrated presence of splints around the left and right bronchi in Patient 2 at 1 month. Note that the patient had bilateral mainstem bronchomalacia and received a tracheobronchial splint on both the left and right mainstem bronchus. (D) Pre-operative (top) and 1 month post-operative (bottom) CT images of Patient 3.

Fig. 3. PEEP, albumin, and immunoglobulin levels of patients after splint

Time 0 on the x-axis of all graphs is the day of tracheobronchial splint implantation. (A) Control charts of positive end expiratory pressure (PEEP) ventilatory requirements for Patients 1–3 over time. Solid line denotes the steady-state mean and the dashed lines denote upper and lower control limits. Comparison of pre-operative and post-operative PEEP requirements was performed using a Wilcoxon signed rank test (α=0.05, two-sided). (B) Control chart of PEEP ventilatory requirement, control chart of serum albumin measurement, and run chart of serum immunoglobulin G (IgG) measurement over time for Patient 2. Solid lines denote the steady-state mean and the dashed lines denote upper and lower control limits. Red arrows denote days intravenous albumin or intravenous IgG was administered.

Fig. 4. Mean airway caliber over time

Patient airway hydraulic diameter (D_H) was measured over time after implantation of the 3D-printed bioresorbable material. Solid lines denote bronchi that received the tracheobronchial splint. Dashed lines are normal, contralateral bronchi for Patients 1 and 3. All caliber measurements were made on expiratory phase CT imaging using the centerline function of each isolated bronchus in Mimics. The centerline function measures hydraulic diameter every 0.1–1.0 mm along the entire segment of the isolated model. Measurements are represented as averages of all measurements along the length of the isolated affected bronchus model ± SD.