Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs

Author:

Singh Srujan12,Zhou Yuxiao23,Farris Ashley L.23,Whitehead Emma C.23,Nyberg Ethan L.23,O'Sullivan Aine N.23,Zhang Nicholas Y.23,Rindone Alexandra N.23,Achebe Chukwuebuka C.23,Zbijewski Wojciech3,Grundy Will4,Garlick David4,Jackson Nicolette D.5,Kraitchman Dara6,Izzi Jessica M.7,Lopez Joseph8,Grant Michael P.910,Grayson Warren L.1231112ORCID

Affiliation:

1. Department of Chemical and Biomolecular Engineering Johns Hopkins University Baltimore MD 21218 USA

2. Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

3. Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA

4. StageBio Company Mount Jackson VA 22842 USA

5. Inotiv Fort Collins CO 80524 USA

6. Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore MD 21205 USA

7. Department of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD 21205 USA

8. Pediatric Plastic and Reconstructive Surgery, Pediatric Head and Neck Surgery AdventHealth for Children Orlando FL 32803 USA

9. Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore MD 21231 USA

10. Department of Plastic and Reconstructive Surgery R Adams Cowley Shock Trauma Center University of Maryland School of Medicine Baltimore MD 21201 USA

11. Department of Materials Science and Engineering Johns Hopkins University Baltimore MD 21218 USA

12. Institute for Nanobiotechnology Johns Hopkins University Baltimore MD 21218 USA

Abstract

AbstractPorous tissue‐engineered 3D‐printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect‐specific geometry has long been considered an optimal strategy to restore pre‐injury anatomy. However, studies in large animal models have revealed that biomaterial‐induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D‐printed, anatomically‐mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image‐registration workflow is developed to quantify the post‐surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio‐lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long‐term scaffold survivability.

Funder

Maryland Stem Cell Research Fund

National Institutes of Health

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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