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- Pigeot, SébastienUniversity Hospital Basel (author)
Orthotopic Bone Formation by Streamlined Engineering and Devitalization of Human Hypertrophic Cartilage
- Article/chapterEnglish2020
Publisher, publication year, extent ...
- 2020-09-30
- MDPI AG,2020
Numbers
- LIBRIS-ID:oai:lup.lub.lu.se:6b8034c4-6268-447d-bd2a-f6e5e313ae29
- https://lup.lub.lu.se/record/6b8034c4-6268-447d-bd2a-f6e5e313ae29URI
- https://doi.org/10.3390/ijms21197233DOI
Supplementary language notes
- Language:English
- Summary in:English
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- Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, leading to ectopic bone formation. In this study, we aimed at engineering and devitalizing upscaled quantities of HyC ECM within a perfusion bioreactor, followed by in vivo assessment in an orthotopic bone repair model. We hypothesized that the devitalized HyC ECM would outperform a clinical product currently used for bone reconstructive surgery. Human MSC were genetically engineered with a gene cassette enabling apoptosis induction upon addition of an adjuvant. Engineered hMSC were seeded, differentiated, and devitalized within a perfusion bioreactor. The resulting HyC ECM was subsequently implanted in a 10-mm rabbit calvarial defect model, with processed human bone (Maxgraft®) as control. Human MSC cultured in the perfusion bioreactor generated a homogenous HyC ECM and were efficiently induced towards apoptosis. Following six weeks of in vivo implantation, microcomputed tomography and histological analyses of the defects revealed an increased bone formation in the defects filled with HyC ECM as compared to Maxgraft®. This work demonstrates the suitability of engineered devitalized HyC ECM as a bone substitute material, with a performance superior to a state-of-the-art commercial graft. Streamlined generation of the devitalized tissue transplant within a perfusion bioreactor is relevant towards standardized and automated manufacturing of a clinical product.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
- MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Biomaterialvetenskap hsv//swe
- MEDICAL AND HEALTH SCIENCES Medical Biotechnology Biomaterials Science hsv//eng
- Animals
- Apoptosis/genetics
- Bone Remodeling/genetics
- Bone Substitutes/therapeutic use
- Cartilage/growth & development
- Cell Differentiation/genetics
- Extracellular Matrix/genetics
- Humans
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells/cytology
- Osteogenesis/genetics
- Rabbits
- Skull/growth & development
- Tissue Engineering/methods
- Tissue Scaffolds
- Wound Healing/genetics
Added entries (persons, corporate bodies, meetings, titles ...)
- Bourgine, Paul EmileLund University,Lunds universitet,Molekylär skelettbiologi,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Molecular Skeletal Biology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,University Hospital Basel(Swepub:lu)pa2431bo (author)
- Claude, JaquieryUniversity Hospital Basel (author)
- Scotti, CelesteNovartis Institutes for BioMedical Research, Inc.,Istituto Ortopedico Galeazzi (author)
- Papadimitropoulos, AdamUniversity Hospital Basel (author)
- Todorov, AtanasUniversity Hospital Basel (author)
- Epple, ChristianUniversity Hospital Basel (author)
- Peretti, Giuseppe MIstituto Ortopedico Galeazzi,University of Milan (author)
- Martin, IvanUniversity Hospital Basel (author)
- University Hospital BaselMolekylär skelettbiologi (creator_code:org_t)
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- In:International Journal of Molecular Sciences: MDPI AG21:191422-0067
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