Point-of-care treatment of geometrically complex midfacial critical-sized bone defects with 3D-Printed scaffolds and autologous stromal vascular fraction

Srujan Singh; Ethan L Nyberg; Aine N O'Sullivan; Ashley Farris; Alexandra N Rindone; Nicholas Zhang; Emma C Whitehead; Yuxiao Zhou; Eszter Mihaly; Chukwuebuka C Achebe; Wojciech Zbijewski; Will Grundy; David Garlick; Nicolette D Jackson; Takashi Taguchi; Catherine Takawira; Joseph Lopez; Mandi J Lopez; Michael P Grant; Warren L Grayson

doi:10.1016/j.biomaterials.2022.121392

Point-of-care treatment of geometrically complex midfacial critical-sized bone defects with 3D-Printed scaffolds and autologous stromal vascular fraction

Biomaterials. 2022 Mar:282:121392. doi: 10.1016/j.biomaterials.2022.121392. Epub 2022 Feb 1.

Authors

Srujan Singh¹, Ethan L Nyberg², Aine N O'Sullivan², Ashley Farris², Alexandra N Rindone², Nicholas Zhang², Emma C Whitehead², Yuxiao Zhou², Eszter Mihaly², Chukwuebuka C Achebe², Wojciech Zbijewski³, Will Grundy⁴, David Garlick⁴, Nicolette D Jackson⁴, Takashi Taguchi⁵, Catherine Takawira⁵, Joseph Lopez⁶, Mandi J Lopez⁵, Michael P Grant⁷, Warren L Grayson⁸

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Alizée Pathology, LLC, A StageBio Company, Thurmont, MD, USA.
⁵ Department of Veterinary Clinical Sciences, Louisiana State University, Baton Rouge, LA, USA.
⁶ Division of Plastic Surgery, Yale-New Haven Hospital, New Haven, CT, USA.
⁷ Department of Plastic & Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Plastic & Reconstructive Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, USA.
⁸ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: wgrayson@jhmi.edu.

PMID: 35134701
DOI: 10.1016/j.biomaterials.2022.121392

Abstract

Critical-sized midfacial bone defects present a unique clinical challenge due to their complex three-dimensional shapes and intimate associations with sensory organs. To address this challenge, a point-of-care treatment strategy for functional, long-term regeneration of 2 cm full-thickness segmental defects in the zygomatic arches of Yucatan minipigs is evaluated. A digital workflow is used to 3D-print anatomically precise, porous, biodegradable scaffolds from clinical-grade poly-ε-caprolactone and decellularized bone composites. The autologous stromal vascular fraction of cells (SVF) is isolated from adipose tissue extracts and infused into the scaffolds that are implanted into the zygomatic ostectomies. Bone regeneration is assessed up to 52 weeks post-operatively in acellular (AC) and SVF groups (BV/DV = 0.64 ± 0.10 and 0.65 ± 0.10 respectively). In both treated groups, bone grows from the adjacent tissues and restores the native anatomy. Significantly higher torque is required to fracture the bone-scaffold interface in the SVF (7.11 ± 2.31 N m) compared to AC groups (2.83 ± 0.23 N m). Three-dimensional microcomputed tomography analysis reveals two distinct regenerative patterns: osteoconduction along the periphery of scaffolds to form dense lamellar bone and small islands of woven bone deposits growing along the struts in the scaffold interior. Overall, this study validates the efficacy of using 3D-printed bioactive scaffolds with autologous SVF to restore geometrically complex midfacial bone defects of clinically relevant sizes while also highlighting remaining challenges to be addressed prior to clinical translation.

Keywords: 3D printing; Critical-sized bone defects; Decellularized bone; Stromal vascular fraction; Yucatan pigs.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Bone Regeneration
Osteogenesis
Point-of-Care Systems
Printing, Three-Dimensional
Stromal Vascular Fraction*
Swine
Swine, Miniature
Tissue Scaffolds*
X-Ray Microtomography