Human-engineered auricular reconstruction (hEAR) by 3D-printed molding with human-derived auricular and costal chondrocytes and adipose-derived mesenchymal stem cells

Abstract

Microtia is a small, malformed external ear, which occurs at an incidence of 1–10 per 10 000 births. Autologous reconstruction using costal cartilage is the most widely accepted surgical microtia repair technique. Yet, the method involves donor-site pain and discomfort and relies on the artistic skill of the surgeon to create an aesthetic ear. This study employed novel tissue engineering techniques to overcome these limitations by developing a clinical-grade, 3D-printed biodegradable auricle scaffold that formed stable, custom-made neocartilage implants. The unique scaffold design combined strategically reinforced areas to maintain the complex topography of the outer ear and micropores to allow cell adhesion for the effective production of stable cartilage. The auricle construct was computed tomography (CT) scan-based composed of a 3D-printed clinical-grade polycaprolactone scaffold loaded with patient‐derived chondrocytes produced from either auricular cartilage or costal cartilage biopsies combined with adipose-derived mesenchymal stem cells. Cartilage formation was measured within the construct in vitro, and cartilage maturation and stabilization were observed 12 weeks after its subcutaneous implantation into a murine model. The proposed technology is simple and effective and is expected to improve aesthetic outcomes and reduce patient discomfort.

Cartilage Tissue Engineering for Nasal Alar and Auricular Reconstruction: A Critical Review of the Literature and Implications for Practice in Dermatologic Surgery

“…Landau and colleagues 46 designed a unique 3D-printed biodegradable PCL auricle scaffold seeded with auricular or costal chondrocytes cocultured with mesenchymal stem cells in vitro. Twelve weeks postimplantation into a murine model, cartilage maturation and stabilization were observed.…”

Optimization of 3D autologous chondrocyte-seeded polyglycolic acid scaffolds to mimic human ear cartilage

“…36 Literature describes that it is required to obtain 150 million cells at least for seeding an entire engineered 3D-printed or molded Paper Biomaterials Science ear. 37,38 Massive expansion is essential for that number cells. However, it is to reach such cell numbers with only two passages (needed for keeping the chondrocyte phenotype).…”

Genetically engineered chondrocytes overexpressing elastin improve cell retention and chondrogenesis in a three‐dimensional GelMA culture system

“…Exogenous elastin has been added to the scaffold to mimic native elastic cartilage, but its insoluble and nondegradable properties hinder extracellular matrix (ECM) assemblement and rearrangement, which would hinder cell proliferation and migration (Nürnberger et al, 2019; P. Tang et al, 2021; Visscher et al, 2021). Although chondrocytes originating from different types of cartilage are reported to synthesize corresponding cartilage ECM, endogenous elastic fiber production by isolated auricular chondrocytes is insufficient (Landau et al, 2021). Many approaches have been explored to improve cartilage regeneration, whereas less emphasis has been placed on elastic fiber production (Akay et al, 2010; Cohen et al, 2018; Jessop et al, 2016; Oh et al, 2018; Posniak et al, 2022; M. Wang et al, 2020).…”

“…originating from different types of cartilage are reported to synthesize corresponding cartilage ECM, endogenous elastic fiber production by isolated auricular chondrocytes is insufficient (Landau et al, 2021). Many approaches have been explored to improve cartilage regeneration, whereas less emphasis has been placed on elastic fiber production (Akay et al, 2010;Cohen et al, 2018;Jessop et al, 2016;Oh et al, 2018;Posniak et al, 2022;M.…”