Osteoinductive 3D printed scaffold healed 5\xa0cm segmental bone defects in the ovine metatarsus

Yunzhi Peter Yang,William Maloney,Michael J Gardner,Kevin M Labus,Jiannan Li,Benjamin C Gadomski,Elaine Lui,Christian M Puttlitz,Sungwoo Kim,Brad Nelson,Daniel Regan,Ross H Palmer,Alexander Stahl,Seyedsina Moeinzadeh,Jeremiah Easley,Arnaud Bruyas,Kirk Mcgilvray

doi:10.1038/s41598-021-86210-5

Yunzhi Peter Yang, William Maloney + Show 15 more

Open Access

https://doi.org/10.1038/s41598-021-86210-5

Copy DOI

Journal: Scientific Reports	Publication Date: Mar 23, 2021
Citations: 20	License type: open-access

Affiliation: Stanford University, Colorado State University

Abstract

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Highlights

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair
We previously developed 3D printed biodegradable scaffolds made from a composite of polycaprolactone (PCL) and β-tricalcium phosphate (β-TCP) for bone regrowth
We designed and 3D printed a novel PCL/β-TCP scaffold with a central channel for intramedullary nail fixation and a side hook to hold and stabilize Infuse Recombinant human bone morphogenetic protein 2 (rhBMP-2) collagen sponges (Fig. 1)

Summary

Introduction

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. Autologous bone grafts generally demonstrate the greatest regenerative potential for tissue repair but are hampered by limited availability and significant complications at the donor site. Though PCL/β-TCP scaffolds provide structural support for the deposition of actively regenerating bone tissues, the ability of the scaffold material to promote new bone growth is limited. We hypothesize that incorporation of the rhBMP-2 delivery system within a rigid PCL/β-TCP scaffold may yield an engineered bone graft with greater regenerative potential than either component alone

Methods

Results

Conclusion