Bone‐on‐a‐Chip: Microfluidic Technologies and Microphysiologic Models of Bone Tissue

Abstract

Bone is an active organ that continuously undergoes an orchestrated process of remodeling throughout life. Bone tissue is uniquely capable of adapting to loading, hormonal, and other changes happening in the body, as well as repairing bone that becomes damaged to maintain tissue integrity. On the other hand, diseases such as osteoporosis and metastatic cancers disrupt normal bone homeostasis leading to compromised function. Historically, the ability to investigate processes related to either physiologic or diseased bone tissue is limited by traditional models that fail to emulate the complexity of native bone. Organ‐on‐a‐chip models are based on technological advances in tissue engineering and microfluidics, enabling the reproduction of key features specific to tissue microenvironments within a microfabricated device. Compared to conventional in vitro and in vivo bone models, microfluidic models, and especially organ‐on‐a‐chip platforms, provide more biomimetic tissue culture conditions, with increased predictive power for clinical assays. In this review, microfluidic and organ‐on‐a‐chip technologies designed for understanding the biology of bone as well as bone‐related diseases and treatments are reported. Finally, the authors discuss the limitations of the current models and point toward future directions for microfluidics and organ‐on‐a‐chip technologies in bone research.

Measurement of Biomimetic Deposition of Calcium Phosphate in Real Time Using Complex Capacitance

“…[26] However, the translation of EIS studies of bone formation in vivo to the microfluidic environment, with its attendant advantages in terms of reduced reagent volume and the potential for high-throughput and automated studies, [27] remains relatively limited, in part because "bone on chip" models are a relatively immature field in comparison with microfluidic models of other tissues and organs. [28] Investigations of the deposition of mineral on chip under biomimetic conditions using impedance have so far been limited to measurements at a single frequency and a single timepoint. [29] These measurements do not take full advantage of the benefits of EIS, both in terms of the potential to perform automated time-series measurements due to the noninvasive nature of the technique and in terms of the amount of information that can be obtained from a single measurement by performing a frequency sweep.…”

“…However, the translation of EIS studies of bone formation in vivo to the microfluidic environment, with its attendant advantages in terms of reduced reagent volume and the potential for high‐throughput and automated studies, [ 27 ] remains relatively limited, in part because “bone on chip” models are a relatively immature field in comparison with microfluidic models of other tissues and organs. [ 28 ]…”

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

“…NP cells, AF cells, neurons and endothelial cells); 2) allow the long-term preservation of mice IVDs; and 3) expose IVD cells to physical stimuli such as shear stresses or electrical impulses. While various OoC models are available for other musculoskeletal tissues (for instance bone-on-chip models as reviewed by Mansoorifar et al (2021)), the application of this technology to the IVD field is still relatively budding and progress will be needed to develop representative IVD models. New mechanically active OoCs can be designed, or existing OoCs developed for other purposes could be repurposed for the replication of IVD loading.…”

A vascularized bone-on-a-chip model development via exploring mechanical stimulation for evaluation of fracture healing therapeutics

“…Specifically, the pharmaceutical industries working in the area of osteogenic diseases such as rickets, osteoporosis, osteoarthritis, and orthopedic trauma are highly interested in the development of in vitro bone models. [35] While there are certain in vitro bone models that exist in literature, most of them fail to mimic multiple features. Bone is a mechanoresponsive tissue.…”