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Cited by 339Bone Tissue Engineering MaterialsTissue Engineering and Regenerative MedicineBone fractures and treatments

In vivo engineering of organs: The bone bioreactor

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Stevens, Molly M., Marini, Robert P., Schaefer, Dirk, Aronson, Joshua, Langer, Robert, Shastri, V. Prasad·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0504705102PMC PMC1183576
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Abstract

Treatment of large defects requires the harvest of fresh living bone from the iliac crest. Harvest of this limited supply of bone is accompanied by extreme pain and morbidity. This has prompted the exploration of other alternatives to generate new bone using traditional principles of tissue engineering, wherein harvested cells are combined with porous scaffolds and stimulated with exogenous mitogens and morphogens in vitro and/or in vivo. We now show that large volumes of bone can be engineered in a predictable manner, without the need for cell transplantation and growth factor administration. The crux of the approach lies in the deliberate creation and manipulation of an artificial space (bioreactor) between the tibia and the periosteum, a mesenchymal layer rich in pluripotent cells, in such a way that the body's healing mechanism is leveraged in the engineering of neotissue. Using the "in vivo bioreactor" in New Zealand White rabbits, we have engineered bone that is biomechanically identical to native bone. The neobone formation followed predominantly an intramembraneous path, with woven bone matrix subsequently maturing into fully mineralized compact bone exhibiting all of the histological markers and mechanical properties of native bone. We harvested the bone after 6 weeks and transplanted it into contralateral tibial defects, resulting in complete integration after 6 weeks with no apparent morbidity at the donor site. Furthermore, in a proof-of-principle study, we have shown that by inhibiting angiogenesis and promoting a more hypoxic environment within the "in vivo bioreactor space," cartilage formation can be exclusively promoted.

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Authors
Stevens, M. M., Marini, R. P., Schaefer, D., Aronson, J., Langer, R., & Shastri, V. P.
Affiliations
  • University of Basel (CH)
  • Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton Street, E25-342, Cambridge, MA 02139; Department of Materials, Imperial College London, Prince Consort Road, London SW7 2AZ, United Kingdom; Division of Comparative Medicine, Massachusetts Institute of Technology, 45 Carleton Street, E25-021, Cambridge, MA 02139; Department of Surgery, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland; and Department of Biomedical Engineering, Vanderbilt University,...
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-07-29
Volume
102
Issue
32
Pages
11450-11455
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0504705102
PMC
PMC1183576
OpenAlex
W2151420872
Cited by
339
References
43
Citations by year
2026: 3 · 2025: 6 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 15 · 2020: 15 · 2019: 11 · 2018: 13 · 2017: 20 · 2016: 21 · 2015: 14 · 2014: 10 · 2013: 24 · 2012: 28
FWCI
11.60
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
Keywords
bone tissue engineering, in vivo bioreactor, bone defect repair, periosteum, intramembranous ossification, woven bone, bone grafting, angiogenesis inhibition, hypoxia, chondrogenesis, rabbit model
MeSH terms
Alginates, Animals, Hexuronic Acids, Histological Techniques, Hyaluronic Acid, Organ Culture Techniques, Periosteum, Rabbits, Radiography, Tibia, Bone Transplantation, Bioreactors, Glucuronic Acid, Tissue Engineering

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