Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region-Dependent Porosity Gradients in an Equine Model.
Abstract: The clinical translation of three-dimensionally printed bioceramic scaffolds with tailored architectures holds great promise toward the regeneration of bone to heal critical-size defects. Herein, the long-term in vivo performance of printed hydrogel-ceramic composites made of methacrylated-oligocaprolactone-poloxamer and low-temperature self-setting calcium-phosphates is assessed in a large animal model. Scaffolds printed with different internal architectures, displaying either a designed porosity gradient or a constant pore distribution, are implanted in equine tuber coxae critical size defects. Bone ingrowth is challenged and facilitated only from one direction via encasing the bioceramic in a polycaprolactone shell. After 7 months, total new bone volume and scaffold degradation are significantly greater in structures with constant porosity. Interestingly, gradient scaffolds show lower extent of remodeling and regeneration even in areas having the same porosity as the constant scaffolds. Low regeneration in distal regions from the interface with native bone impairs ossification in proximal regions of the construct, suggesting that anisotropic architectures modulate the cross-talk between distant cells within critical-size defects. The study provides key information on how engineered architectural patterns impact osteoregeneration in vivo, and also indicates the equine tuber coxae as promising orthotopic model for studying materials stimulating bone formation.
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication Date: 2020-04-23 PubMed ID: 32324336PubMed Central: PMC7116206DOI: 10.1002/adhm.201901807Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores the use of three-dimensionally printed bioceramic scaffolds to regenerate bone to heal significant defects. It compares the effectiveness of scaffolds with different internal structures in an equine model over a period of 7 months.
Objective
The study aimed to compare the bone regeneration properties of two types of 3D printed scaffolds, one with constant porosity and the other with a porosity gradient. The use of these scaffolds were tested in equine bone defect models to understand the most suitable architecture for fostering bone regeneration.
Materials and Methods
- The hydrogel-ceramic composites used for creating the scaffolds were made from methacrylated-oligocaprolactone-poloxamer and low-temperature self-setting calcium-phosphates.
- Two types of scaffolds were printed: one with a designed gradient of porosity (variable hole sizes) and the other with a consistent distribution of pores.
- The scaffolds were implanted in subjects with defects in the equine tuber coxae bone. Bone growth was directed from one side by encasing the bioceramic scaffold in a polycaprolactone shell, creating a controlled environment for bone growth.
Results
- After 7 months, it was found that scaffolds with a constant porosity resulted in significantly more bone volume and scaffold degradation than gradient scaffolds.
- Interestingly, even areas of gradient scaffolds with porosity similar to the constant scaffolds showed lesser remodeling and regeneration.
- The study also found an apparent relation between the level of bone regeneration in distant regions of the scaffolds and their proximity to the interface with native bone.
Conclusion and Future Direction
- The study concluded that scaffold architectural patterns have a significant impact on the process of bone regeneration. Organs with constant porosity seem to be more beneficial for bone volume growth than those with gradient porosity.
- This research indicates that anisotropic architectures impact cell activity across critical-size defects, affecting the overall regrowth rate of bone.
- The study also deemed the equine tuber coxae a promising model for researching materials encouraging bone formation.
Cite This Article
APA
Diloksumpan P, Bolaños RV, Cokelaere S, Pouran B, de Grauw J, van Rijen M, van Weeren R, Levato R, Malda J.
(2020).
Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region-Dependent Porosity Gradients in an Equine Model.
Adv Healthc Mater, 9(10), e1901807.
https://doi.org/10.1002/adhm.201901807 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Escuela de Medicina Veterinaria, Universidad Nacional Costa Rica, Barreal de Heredia, Heredia, Lagunilla, 86-3000, Costa Rica.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Department of Orthopaedics and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Department of Orthopaedics and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Department of Orthopaedics and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht, 3584 CL, The Netherlands.
- Department of Orthopaedics and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
MeSH Terms
- Animals
- Bone Regeneration
- Horses
- Osteogenesis
- Porosity
- Printing, Three-Dimensional
- Tissue Scaffolds
Grant Funding
- 647426 / European Research Council
Conflict of Interest Statement
. The authors declare no conflict of interest.
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