Pick Your Nose: Customizable, Low-cost, Biocompatible Implants for Craniofacial Reconstruction

PURPOSE: Craniofacial reconstruction or enhancement requires autologous, cadaveric or alloplastic implants, often requiring intraoperative modification to optimize shape and fit for a particular patient, introducing associated risks of infection, extrusion, expense and donor site morbidity. Given these shortcomings, there is substantial need for biocompatible, customizable and low-cost facial implants. This study examines the biocompatibility and durability of various polylactic acid (PLA) implant designs +/- decellularized cartilage infill to assess translatability to craniofacial (nasal) reconstruction. METHODS & MATERIALS: Cartilage harvested from ovine ribs was minced or zested and decellularized. Dorsal nasal scaffolds with contours similar to commercially available silicone dorsal nasal implants were custom-designed with 3D modeling software and printed in polylactic acid (PLA) on a PRUSA i3 MK3S+ printer. All scaffolds were heterotopically implanted on rat dorsa with 4 implants per rat. Two scaffolds designed as external “cages” of low or high porosity and were without internal supports. These cages were implanted empty or with processed decellularized cartilage (either “minced” or “zested”) infill, yielding 6 total treatment groups, n=4 each. The remaining two scaffolds were designed with internal PLA rebar supports and implanted without decellularized cartilage infill. Scaffolds were explanted 3, 6 and 12 months after implantation, after which they underwent same-day volumetric analysis via microCT. Explants were then Formalin-fixed, embedded in paraffin and sectioned for histopathologic and immunohistochemistry analysis. Statistical and image analysis was completed on RStudio and ImageJ. RESULTS: Overall, implant contours were best retained across all timepoints in the low and high porosity rebar groups. Empty and zested cartilage-filled cages had significant volume loss at 6 and 12 months relative to volume at implant (p < 0.05) with explanted constructs grossly collapsed at both timepoints. Rebar and minced cartilage-filled constructs had superior volume retention relative to empty and zested cartilage-filled cages at 6 months; only rebar groups retained this volume after one year (p < 0.05). Uniform and well-distributed neotissue ingrowth was evident in all filled implants on MicroCT; “cage” implants without infill no longer had a measurable internal cavity volume due to flattening. Hematoxylin and eosin and safranin-O stain showed a robust lymphocytic inflammatory response at 3 months that subsided by 6 and 12 months, as well as increased tissue vascularization and collagen deposition between timepoints consistent with healthy tissue ingrowth. Immunostaining indicated an environment favorable to tissue proliferation with more M2 than M1 macrophages across all timepoints and strong M2 expression among the cells bordering PLA. CONCLUSION: This study supports the use of PLA for generating customizable facial implants. With sufficient internal supports, constructs retain contours and volume at one-year post-implant and provide a scaffold for ingrowth of healthy, vascularized, collagen-rich tissue. While volume retention for decellularized cartilage-filled cages was inferior to PLA-only groups, these findings support the biocompatibility of combined decellularized cartilage-PLA implants and future designs may incorporate both rebar and cartilage infill. Importantly, design and fabrication of these bespoke implants can be completed quickly and at minimal cost, potentially at the point of care, allowing for affordable implants with a minimal risk profile.