No abstract

No abstract

BackgroundBone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry. MethodsHere, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs). Structural components included 3D β-tricalcium phosphate (β-TCP) scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM.ResultsIn vitro, β-TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation.ConclusionsOur tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0234-9) contains supplementary material, which is available to authorized users.

Complex 3D scaffolds with interconnected pores are a promising tool for bone regeneration. Such 3D scaffolds can be manufactured by selective laser sintering (SLS) from biodegradable composite powders. However, the mechanical strength of these scaffolds is often too low for medical application. We propose that the mechanical strength of laser-sintered scaffolds can be improved through composite powders with tailored properties (e.g., suitable powder particle size and melt viscosity for SLS). To prove this, two batches of a poly(D,L-lactide) (PDLLA)/β-tricalcium phosphate (β-TCP) composite powder with 50 wt% PDLLA and 50 wt% β-TCP were synthesized. The two batches differed in polymer particle size, filler particle size, and polymer molecular weight. Both batches were processed with identical SLS process parameters to study the extent to which the material properties influence how well a PDLLA/β-TCP (50/50) composite can be processed with SLS. In the SLS process, batch 2 showed improved melting behavior due to its smaller polymer particle size (approx. 35 µm vs. 50 µm) and its lower zero-shear melt viscosity (5800 Pa∙s vs. 17,900 Pa∙s). The better melting behavior of batch 2 led to SLS test specimens with lower porosity compared to batch 1. In consequence, the batch 2 specimens exhibited a larger biaxial bending strength (62 MPa) than the batch 1 specimens did (23 MPa). We conclude that a tailored composite powder with optimized polymer particle size, filler particle size, and polymer molecular weight can increase the achievable mechanical strength of laser-sintered scaffolds.