Lab-on-a-chip platforms for quantification of multicellular interactions in bone remodeling

George, Estee L.; Truesdell, Sharon L.; York, Spencer L.; Saunders, Marnie M.

doi:10.1016/j.yexcr.2018.02.027

Cited by 32 publications

(24 citation statements)

References 34 publications

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“…A few promising studies have been published in the field of bone-on-a chip studies. The group of Marnie Saunders has developed a microfluidic system, which allows the analysis of osteoblasts or osteoclasts in response to osteocyte-conditioned medium [ 28 , 29 ]. Middleton et al co-cultivated osteocytes and osteoclasts in a microfluidic system and demonstrated an increased mechano-response of osteocytes in co-culture with osteoclasts [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model

Bernhardt

Skottke

Witzleben

et al. 2021

IJMS

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In vitro evaluation of bone graft materials is generally performed by analyzing the interaction with osteoblasts or osteoblast precursors. In vitro bone models comprising different cell species can give specific first information on the performance of those materials. In the present study, a 3D co-culture model was established comprising primary human osteoblasts, osteoclasts and osteocytes. Osteocytes were differentiated from osteoblasts embedded in collagen gels and were cultivated with osteoblast and osteoclasts seeded in patterns on a porous membrane. This experimental setup allowed paracrine signaling as well as separation of the different cell types for final analysis. After 7 days of co-culture, the three cell species showed their typical morphology and gene expression of typical markers like ALPL, BSPII, BLGAP, E11, PHEX, MEPE, RANKL, ACP5, CAII and CTSK. Furthermore, relevant enzyme activities for osteoblasts (ALP) and osteoclasts (TRAP, CTSK, CAII) were detected. Osteoclasts in triple culture showed downregulated TRAP (ACP5) and CAII expression and decreased TRAP activity. ALP and BSPII expression of osteoblasts in triple culture were upregulated. The expression of the osteocyte marker E11 (PDPN) was unchanged; however, osteocalcin (BGLAP) expression was considerably downregulated both in osteoblasts and osteocytes in triple cultures compared to the respective single cultures.

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Section: Discussionmentioning

confidence: 99%

Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model

Bernhardt

Skottke

Witzleben

et al. 2021

IJMS

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“…MPS modelling of bone remodelling is in its nascency. George et al fabricated remodelling on chip applications using a PDMS device that could mechanically stimulate osteocytes and provide flow conditioned media to cultures of osteoblasts and osteocytes [215].…”

Section: Bone Remodellingmentioning

confidence: 99%

Biofabrication of vasculature in microphysiological models of bone

et al. 2021

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Bone contains a dense network of blood vessels that are essential to its homoeostasis, endocrine function, mineral metabolism and regenerative functions. In addition, bone vasculature is implicated in a number of prominent skeletal diseases, and bone has high affinity for metastatic cancers. Despite vasculature being an integral part of bone physiology and pathophysiology, it is often ignored or oversimplified in in vitro bone models. However, 3D physiologically relevant vasculature can now be engineered in vitro, with microphysiological systems (MPS) increasingly being used as platforms for engineering this physiologically relevant vasculature. In recent years, vascularised models of bone in MPSs systems have been reported in the literature, representing the beginning of a possible technological step change in how bone is modelled in vitro.Vascularised bone MPSs is a subfield of bone research in its nascency, however given the impact of MPSs has had in in vitro organ modelling, and the crucial role of vasculature to bone physiology, these systems stand to have a substantial impact on bone research. However, engineering vasculature within the specific design restraints of the bone niche is significantly challenging given the different requirements for engineering bone and vasculature. With this in mind, this paper aims to serve as technical guidance for the biofabrication of vascularised bone tissue within MPS devices. We first discuss the key engineering and biological considerations for engineering more physiologically relevant vasculature in vitro within the specific design constraints of the bone niche. We next explore emerging applications of vascularised bone MPSs, and conclude with a discussion on the current status of vascularised bone MPS biofabrication and suggest directions for development of next generation vascularised bone MPSs.

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“…Immune system [50,71], bone [116,117], breast tissue [118,119], pancreas [120,121], bladder, reproductive tract [104], skin [13].…”

Section: Othersmentioning

confidence: 99%

Organ-on-a-Chip systems for new drugs development

2021

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Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

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Lab-on-a-chip platforms for quantification of multicellular interactions in bone remodeling

Cited by 32 publications

References 34 publications

Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model

Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model

Biofabrication of vasculature in microphysiological models of bone

Organ-on-a-Chip systems for new drugs development

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