Research ArticleAPPLIED SCIENCES AND ENGINEERING

3D printing of a wearable personalized oral delivery device: A first-in-human study

See allHide authors and affiliations

Science Advances  09 May 2018:
Vol. 4, no. 5, eaat2544
DOI: 10.1126/sciadv.aat2544
  • Fig. 1 Workflow for the manufacture of wearable personalized oral delivery mouthguards by 3D printing.

    The manufacture of personalized oral delivery mouthguards by 3D printing involved two stages. In the data acquisition stage, we obtained an intraoral scan of the maxillary anatomy of the subject and the impression served as the template for 3D printing. 3D manufacture began with the production of printable pharmaceutical-grade (PG) filaments loaded with the desired compound by hot melt extrusion (HME). We obtained filaments with tunable release rates by adjusting the polymer composition in the feed and subsequently used them to fabricate prototypes with customizable designs (based on the scanned templates) by FDM-based 3D printing. Finally, we evaluated the performance of the personalized 3D-printed mouthguard on each individual.

  • Fig. 2 Selection of compound-loaded filaments with tunable release properties for 3D printing.

    (A) Chemical structures of CBS and VA. (B) TGA thermograms of CBS and VA. (C) Loading efficiencies of CBS and VA in the filaments after HME. PVA (high) and PVA (low) represent PVA/PLA feed weight ratios of 6:3 and 5:4, respectively, for CBS and ratios of 2:3 and 1:3, respectively, for VA. (D and E) Cumulative release of the CBS-loaded (D) and the VA-loaded (E) filaments in vitro. (F) Weight loss of the CBS-loaded and VA-loaded filaments after the in vitro dissolution study. Data are means ± SD (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

  • Fig. 3 Characterizations of filaments loaded with either CBS or VA.

    (A and B) DSC thermograms of pure CBS (A), filaments consisting of only PLAS or PVAS, CBS-loaded PVA (high), and PVA (low) filaments, and pure VA (B), filaments consisting of only PLAPG or PVAPG, as well as VA-loaded PVA (high) and PVA (low) filaments. (C and D) XRPD diffractograms of the same compounds and filaments as in (A) [for (C)] and (B) [for (D)]. (E) SEM images of filaments loaded with either CBS or VA: surface, cross section, and a magnified view of the cross section. Scale bars, 100 μm (for surface and cross section) and 10 μm (for a magnified view of the cross section). (F and G) Stress-strain curve of PLAS, PVAS, and CBS-loaded filaments (F) and PLAPG, PVAPG, and VA-loaded filaments (G).

  • Fig. 4 3D printing of mouthguards loaded with either CBS or VA that have tunable release properties.

    (A) Image of a 3D-printed mouthguard comprising a CBS-free top (red) and CBS-containing base (off-white) fabricated using PLAS filament and PVA (high) CBS-loaded filament, respectively. (B) Image of a 3D-printed mouthguard comprising a VA-free top (white) and VA-containing base (off-white) fabricated using PLAPG/PVAPG (9:1, w/w) filament and PVA (high) VA-loaded filament, respectively. (C) Amount of residual CBS and VA in the mouthguards following 3D printing using the CBS-loaded and VA-loaded filaments. (D and E) Cumulative release of the CBS-loaded (D) and VA-loaded (E) mouthguards in vitro. (F) Images of the CBS-loaded and VA-loaded mouthguards before and after the in vitro dissolution study. A distinct whitening of the regions containing the CBS or VA occurred. (G) Weight loss of the CBS-loaded and VA-loaded mouthguards after the in vitro dissolution study. (H) Amount of residual CBS and residual VA in the mouthguards after the in vitro dissolution study. Data are means ± SD (n = 3). **P < 0.01, ***P < 0.001, and ****P < 0.0001.

  • Fig. 5 3D printing of tailored VA-loaded mouthguards for the first-in-human study and evaluation of VA release in the saliva.

    (A) 3D-printed VA-loaded mouthguards with three different designs: HSPH, VSPH, and HSPL. (B) Representative images of the 3D-printed VA-loaded mouthguards tailored to each volunteer’s maxillary anatomy in the HSPH group. (C and D) Mean VA concentrations in the saliva of volunteers wearing mouthguards of the three designs during the first cycle (C) and second cycle (D) of wearing for 2 hours continuously. (E) Amount of residual VA in the mouthguards following three cycles of wearing by the volunteers. Box-and-whisker plot showing median (horizontal line), interquartile range (box), minimum and maximum of all of data (whiskers). (F) Representative images of each of the three types of VA-loaded mouthguards before and after three cycles of wearing by the same volunteer. A distinct whitening of the region containing VA was observed, as indicated by the arrows. Data for C and D are means ± SD (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/4/5/eaat2544/DC1

    fig. S1. Selection of active compound and polymer blends for HME.

    fig. S2. Optimization of PVAS/PLAS ratio for CBS-loaded filaments.

    fig. S3. Thermal properties of CBS-loaded and VA-loaded filaments.

    fig. S4. Characterizations of polymer mixtures containing CBS or VA.

    fig. S5. Surface and cross-section of unloaded filaments.

    fig. S6. Optimization of temperature for 3D printing.

    fig. S7. Evaluation of the VA concentration and the weight of the mouthguards.

    fig. S8. Release profiles of the personalized mouthguards in vitro.

    table S1. Physicochemical properties of CBS and VA.

    table S2. Feed compositions for the prepared blend filaments and the CBS loading efficiencies for the corresponding filaments.

    table S3. Solubility parameter calculations of individual components of the filaments based on the Hoftyzer and Van Krevelen method and the Hoy method.

    table S4. Mechanical properties of pure PLAS filaments, pure PVAS filaments, and the CBS-loaded blend filaments.

    table S5. Mechanical properties of pure PLAPG, PVAPG filaments, and the VA-loaded blend filaments.

    table S6. Optimization of the filament temperature and composition for the VA-free region in the mouthguard.

    table S7. AUC of VA concentrations in saliva after each cycle of wearing of the three different mouthguards.

    Methods

    movie S1. Movie summarizing the different steps involved in the preparation of the 3D-printed compound-eluting mouthguards.

    Reference (49, 50)

  • Supplementary Materials

    This PDF file includes:

    • fig. S1. Selection of active compound and polymer blends for HME.
    • fig. S2. Optimization of PVAS/PLAS ratio for CBS-loaded filaments.
    • fig. S3. Thermal properties of CBS-loaded and VA-loaded filaments.
    • fig. S4. Characterizations of polymer mixtures containing CBS or VA.
    • fig. S5. Surface and cross-section of unloaded filaments.
    • fig. S6. Optimization of temperature for 3D printing.
    • fig. S7. Evaluation of the VA concentration and the weight of the mouthguards.
    • fig. S8. Release profiles of the personalized mouthguards in vitro.
    • table S1. Physicochemical properties of CBS and VA.
    • table S2. Feed compositions for the prepared blend filaments and the CBS loading efficiencies for the corresponding filaments.
    • table S3. Solubility parameter calculations of individual components of the filaments based on the Hoftyzer and Van Krevelen method and the Hoy method.
    • table S4. Mechanical properties of pure PLAS filaments, pure PVAS filaments, and the CBS-loaded blend filaments.
    • table S5. Mechanical properties of pure PLAPG, PVAPG filaments, and the VA-loaded blend filaments.
    • table S6. Optimization of the filament temperature and composition for the VA-free region in the mouthguard.
    • table S7. AUC of VA concentrations in saliva after each cycle of wearing of the three different mouthguards.
    • Methods
    • References (49, 50)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • movie S1 (.mp4 format). Movie summarizing the different steps involved in the preparation of the 3D-printed compound-eluting mouthguards.

    Files in this Data Supplement: