Magnetically actuated bone scaffold: Microstructure, cell response and osteogenesis

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

It is essential to determine the biodistribution, clearance, and biocompatibility of magnetic nanoparticles (MNPs) for in vivo biomedical applications to ensure their safe clinical use. We have studied these aspects with our novel iron oxide MNP formulation, which can be used as a magnetic resonance imaging (MRI) agent and a drug carrier system. Changes in serum and tissue iron levels were analyzed over 3 weeks after intravenous administration of MNPs to rats. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) levels, and total iron-binding capacity (TIBC) were also measured with time to assess the effect of MNPs on liver function. Selected tissues were also analyzed for oxidative stress and studied histologically to determine biocompatibility of MNPs. Serum iron levels gradually increased for up to 1 week but levels slowly declined thereafter. Biodistribution of iron in various body tissues changed with time but greater fraction of the injected iron localized in the liver and spleen than in the brain, heart, kidney, and lung. Magnetization measurements of the liver and spleen samples showed a steady decrease over 3 weeks, suggesting particle degradation. Serum showed a transient increase in ALT, AST, AKP levels, and TIBC over a period of 6-24 h following MNP injection. The increase in oxidative stress was tissue dependent, reaching a peak at approximately 3 days and then slowly declining thereafter. Histological analyses of liver, spleen, and kidney samples collected at 1 and 7 days showed no apparent abnormal changes. In conclusion, our MNPs did not cause long-term changes in the liver enzyme levels or induce oxidative stress and thus can be safely used for drug delivery and imaging applications.