Processing of biphasic calcium phosphate ceramics for culturing of bone marrow stem cells
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Ian Nettleshipa) Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261; and McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261 (Received 20 December 2016; accepted 3 March 2017)
Ceramic scaffolds are being developed to control both proliferation and differentiation of hematopoietic stem cells into desired cell products in bioreactors. These scaffolds mimic important aspects of the microenvironment or “niche” inside bone marrow. In particular, hematopoietic stem cell fate is thought to be effected by the architecture of trabecular bone and the presence of calcium. Here we report the effects of ceramics processing on the phase distribution and microstructure of biphasic ceramics used to culture hematopoietic stem cells. Processing of biphasic ceramics by powder mixing resulted in tetracalcium phosphate on the sintered surface. This correlated with observed surface deposits, weight gain, and the release of calcium ions in saline over 28 days. In contrast, impregnation of partially sintered hydroxyapatite with calcium nitrate resulted in calcium carbonate on the sintered surface. Impregnation correlated with the release of calcium ions into the saline, surface pitting, and weight loss. I. INTRODUCTION
Tissue engineering is one of the most important approaches to tissue replacement and organ repair including bone repair,1,2 eye transplantation,3 and heart transplantation.4 In tissue engineering, bioreactors can play a key role is the expansion of stem cell populations required for repair and also cell populations required for cell therapies. The hematopoietic stem cells (HSCs) have been unquestionably important to therapies that involve blood and immune system replacement, including myeloma5 and leukemia.6 HSCs are of central importance to hematopoiesis and the formation of hematopoietic tissue in red bone marrow. They have the ability to replenish all cellular components of blood and to self-renew.7 In bone marrow, HSCs reside in the endosteal niche, a microenvironment close to the surface of the highly porous trabecular bone located in the interior of large bones such as the femur. Once released from the endosteal niche, HSCs begin to differentiate. The HSCs in the endosteal niche live in association with a range of stromal cells known to effect HSC immobilization and control the HSC fate. Of these stromal cells, perhaps the most important are the osteoblast populations.8,9 While there has been much work in this area, there is still much
Contributing Editor: Eugene Medvedovski a) Address all correspondence to this author. e-mail: [email protected] DOI: 10.1557/jmr.2017.106
to learn. Some researchers have demonstrated that osteoblasts are necessary and rate-limiting for the HSC niche function.10,11 If the endosteal niche is to be simulated in a bioreactor core during cell culture, scaffolds that mimic conditions in the niche will also play an important role in HSC maintenance and proliferation.12 The three-dimensional archit
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