A bioartificial and vasculomorphic bone matrix‐based organoid mimicking microanatomy of flat and short bones

Author:

Toni Roberto1234ORCID,Barbaro Fulvio5,Di Conza Giusy5,Zini Nicoletta67,Remaggi Giulia8,Elviri Lisa8,Spaletta Giulia9,Quarantini Enrico4,Quarantini Marco4,Mosca Salvatore10,Caravelli Silvio11,Mosca Massimiliano11,Ravanetti Francesca12,Sprio Simone1,Tampieri Anna1

Affiliation:

1. ISSMC CNR Faenza Italy

2. Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism Tufts Medical Center—Tufts University School of Medicine Boston Massachusetts USA

3. Academy of Sciences of the Institute of Bologna, Section IV—Medical Sciences Bologna Italy

4. Endocrinology, Diabetes, and Nutrition Disorders Outpatient Clinic—OSTEONET (Osteoporosis, Nutrition, Endocrinology, and Innovative Therapies) and Odontostomatology Units Galliera Medical Center San Venanzio di Galliera (BO) Italy

5. Department of Medicine and Surgery—DIMEC, Unit of Biomedical, Biotechnological and Translational Sciences (S.BI.BI.T.), Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), and Museum and Historical Library of Biomedicine—BIOMED University of Parma Parma Italy

6. CNR Institute of Molecular Genetics “Luigi Luca Cavalli‐Sforza” Unit of Bologna Bologna Italy

7. IRCCS Istituto Ortopedico Rizzoli Bologna Italy

8. Food and Drug Department University of Parma Parma Italy

9. Department of Statistical Sciences University of Bologna Bologna Italy

10. Course on Disorders of the Locomotor System, Fellow Program in Orthopaedics and Traumatology University Vita‐Salute San Raffaele Milan Italy

11. II Clinic of Orthopedic and Traumatology IRCCS Istituto Ortopedico Rizzoli Bologna Italy

12. Department of Veterinary Medical Sciences, Section of Anatomy University of Parma Parma Italy

Abstract

AbstractWe engineered an in vitro model of bioartificial 3D bone organoid consistent with an anatomical and vascular microenvironment common to mammalian flat and short bones. To achieve this, we chose the decellularized–decalcified matrix of the adult male rat scapula, implemented with the reconstruction of its intrinsic vessels, obtained through an original intravascular perfusion with polylevolactic (PLLA), followed by coating of the PLLA‐fabricated vascularization with rat tail collagen. As a result, the 3D bone and vascular geometry of the native bone cortical and cancellous compartments was reproduced, and the rat tail collagen–PLLA biomaterial could in vitro act as a surrogate of the perivascular extracellular matrix (ECM) around the wall of the biomaterial‐reconstituted cancellous vessels. As a proof‐of‐concept of cell compatibility and site‐dependent osteoinductive properties of this bioartificial 3D construct, we show that it in vitro leads to a time‐dependent microtopographic positioning of rat mesenchymal stromal cells (MSCs), initiating an osteogenic fate in relation to the bone compartment. In addition, coating of PLLA‐reconstructed vessels with rat tail collagen favored perivascular attachment and survival of MSC‐like cells (mouse embryonic fibroblasts), confirming its potentiality as a perivascular stroma for triggering competence of seeded MSCs. Finally, in vivo radiographic topography of bone lesions in the human jaw and foot tarsus of subjects with primary osteoporosis revealed selective bone cortical versus cancellous involvement, suggesting usefulness of a human 3D bone organoid engineered with the same principles of our rat organoid, to in vitro investigate compartment‐dependent activities of human MSC in flat and short bones under experimental osteoporotic challenge. We conclude that our 3D bioartificial construct offers a reliable replica of flat and short bones microanatomy, and promises to help in building a compartment‐dependent mechanistic perspective of bone remodeling, including the microtopographic dysregulation of osteoporosis.

Publisher

Wiley

Subject

Biomedical Engineering,Biomaterials

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