We 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.
A bioartificial and vasculomorphic bone matrix-based organoid mimicking microanatomy of flat and short bones
Zini N;
2023
Abstract
We 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.