Anatomic-Based Design, Manufacturing, and Preclinical Assessment of a Novel 3D-Printed Bioscaffold for Total Nasal Reconstruction

Introduction

Total nasal reconstruction presents challenges to even the most seasoned surgeon. Large defects typically require a staged paramedian forehead flap for soft tissue coverage.¹ Replication of the nasal tripod architecture is difficult; adult costal cartilage is frequently ossified, requiring high volumes of donor cartilage. In this study, we describe a novel patient-specific anatomic-based approach for nasal reconstruction.^2,3

Methods

The nasal bioscaffold was modeled using a 2.5-μm resolution micro-CT to create a high-resolution digital imaging and communications in medicine and segmented in Mimics and 3-Matics to create a digital model (Materialise, Plymouth, MI) (Fig. 1A–C). A skin overlay was developed using FEBio PreView. Nonlinear finite element analysis was performed using FEBio software to simulate contact between the skin flap (modeled as a nonlinear elastic material) on the nasal bioscaffold to determine the location of high strain concentrations in the skin (Fig. 1E, F).^4,5 Symmetry was optimized, and cartilage inset sites were placed. The model was printed out of polycaprolactone (PCL) with 4% hydroxyapatite using a laser sintering technique to create a biocompatible scaffold capable of evolving into native tissue (Fig. 1D).⁶ After Institutional Review Board exempt determination, the nasal bioscaffold was surgically implanted into a male human cadaver. Both the open septorhinoplasty approach and total nasal defect and reconstruction utilizing a forehead flap for soft tissue coverage and pericranial flap for internal mucosal lining were tested.

Fig. 1.

Anatomic-based total nasal bioscaffold design and nonlinear contact analysis. (A) Human nasal tripod, including subperichondrial dissection of the upper and lower lateral cartilages, septal cartilage, and intracartilaginous ligaments. (B) Micro-CT of total nasal tripod. (C) CAD rendering, which later included cartilage inset sites and predesigned suture holes. (D) GMP manufactured laser sintered PCL bioscaffold with cartilage inset sites and predesigned suture holes. Nonporous and porous bioscaffolds can be produced. (E) Finite element mesh of bioscaffold alone. (F) Strain results from nonlinear contact analysis between nasal bioscaffold and idealized skin flap during simulated stretching of skin flap over nasal bioscaffold. CAD, computer aided design; GMP, good manufacturing practice; PCL, polycaprolactone.

Results

Our manufacturing process consistently and precisely produced 3D-printed nasal bioscaffolds with meticulously preserved anatomy. The contact analysis was run to a 1.5 mm displacement stretch (Fig. 1F). The highest stress areas representing tip defining points on the nasal bioscaffold were revealed on the simulated skin flap. Strains in the outer regions of the skin reached 8%. The strains were lower at the contact points than on the outside of the skin flap due to the bending deformation of the simulated skin. Cartilage inset sites were effectively incorporated in regions of high strain.

The nasal bioscaffold was surgically implanted in the human cadaver to demonstrate nasal aesthetics. An open septorhinoplasty exposed and removed the cadaveric cartilage (Fig. 2A). After forehead flap elevation, nasal bioscaffold incorporation (Fig. 2B), and pericranial flap mucosal lining placement, the prelaminated nasal graft was rotated over the total nasal defect. Seamless integration into the recipient nasal piriform, vomer, and adjacent soft tissue was appreciated (Fig. 2C). The procedure was performed in ∼60 min and would require a second procedure to divide and inset the nasal forehead pedicle.

Fig. 2.

Proposed prelaminated forehead flap, pericranial flap with use of 3D-printed total nasal bioscaffold. (A) Nasal defect after open septorhinoplasty exposed and removed the cadaveric cartilage. (B) In situ placement of 3D-printed total nasal bioscaffold. (C) Completed inferior rotation and inset of total nasal graft using 3D-printed total nasal bioscaffold with overlying paramedian forehead flap and pericranial internal lining, right lateral view.

Discussion

The development of this novel 3D-printed nasal bioscaffold provides a potential solution to the challenges presented by traditional total nasal reconstruction. The scaffold-to-skin contact analysis demonstrated a larger strain on the bioscaffold protuberances, indicating ideal locations for the placement of native cartilage insets. Placement of these insets at high strain locations may reduce vascular strain by creating a softer stiffness gradient and are designed to allow cell proliferation and differention to populate the nose scaffold with the patient's own cells. Robust soft tissue integration and vascularization, seen in our analogous animal models of auricular scaffolds, are intended to mitigate fracture, extrusion, and infection (submitted Hollister, Zopf).

The additive manufacturing of this bioscaffold allows for patient-specific total nasal reconstruction. An expert surgeon can reconstruct a well-sculpted nose over multiple surgical stages requiring cartilage harvest. Our model intends to reduce the number of required surgeries, minimize the amount of donor cartilage necessary, and decrease intraoperative time.

Additional research is needed to determine long-term aesthetic, structural, and soft tissue outcomes in vivo. Development of a testing protocol for Food and Drug Administration submission before human use is underway. Our techniques and scaffold design have intentionally been designed for expedient translation and wide clinical use in a variety of resource settings, including low resource facilities, and thus may reduce complexity and variability of total nasal reconstruction.

Author Disclosure Statement

D.A.Z. is a cofounder of MakeMedical LLC. This entity was created following completion of this work and there are no competing interests.

Funding Information

The University of Michigan has filed a patent application on the nasal tissue scaffold, which is pending, and lists Drs. David A. Zopf and Scott J. Hollister as inventors. The NIH T32 DC005356 grant from the National Institute of Health funded the study of Dr. Chelsea L. Reighard and Ms. Allison R. Powell.