Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

Abstract

Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.

Long-Term Evaluation of Dip-Coated PCL-Blend-PEG Coatings in Simulated Conditions

“…Both bone formation and regeneration of blood vessels ensure the success of implanted metallic devices, in terms of osseointegration and angiogenic functional recovery [66]. The presence of MSCs and ECs at the site of injury play key roles in osteogenic graft integration, enhanced infiltration of these cells ensuring early vascularization and bone formation [76]. The ability of dip-coated blend coatings to establish optimal interactions with both MSCs and ECs was herein demonstrated.…”

Targeting actin-bundling protein L-plastin as an anabolic therapy for bone loss

“…Anti-sclerostin antibody is a new option for bone formation, and further clinical investigations are needed to evaluate its benefits and risks (24). In recent years, anabolic therapeutic strategies for pathological bone loss have attracted attention (25)(26)(27).…”

Biomimetic Mineralization Promotes Viability and Differentiation of Human Mesenchymal Stem Cells in a Perfusion Bioreactor

“…The first step was to optimize hMSC seeding on 3D hybrid scaffolds. Whereas some authors carried out cell seeding in static conditions and then moved cell/scaffold construction inside the bioreactor for dynamic culture [ 46 , 47 , 48 , 49 ], others studies implemented dynamic conditions for cell seeding and culture [ 30 , 50 , 51 ]. Static cell seeding is by far the most commonly used seeding method but it provides low seeding efficiencies and non-uniform cell distribution [ 52 ].…”

“…Several in vivo studies also demonstrated that MSC preconditioning in bioreactor prior to implantation enhanced in vivo results as quantity and quality of new bone [ 23 , 28 , 29 ]. A more recent work demonstrated that bioreactor-based preconditioning augments the bone-forming potential of human bone marrow aspirates [ 30 ].…”