Bone‐on‐a‐Chip: A Microscale 3D Biomimetic Model to Study Bone Regeneration

Abstract

Organ‐on‐chip models, developed using microengineering and microfluidic technologies, aim to recreate physiological‐like microenvironments of organs or tissues as a tool to study (patho)physiological processes in vitro. On‐chip models of bone are relevant for the study of bone physiology, diseases and regenerative processes. While a few bone‐on‐a‐chip models exist, recapitulating the cellular components of bone, these models do not incorporate the chemical and structural characteristics of bone tissue. Herein, the development of a bone‐on‐a‐chip platform is reported that comprises a 3D structural model of bone. To build the platform, first, a 3D model of bone is produced in a polymer using two‐photon polymerization (2PP) from a 3D nano‐computed tomography scan of trabecular bone. This 3D model is then coated with a layer of bone mineral‐like calcium phosphate. Finally, the 3D bone model is integrated inside a microfluidic device suitable for cell culture. Human mesenchymal stromal cells, cultured inside the platform for up to 21 days, show high viability and extensive production of extracellular matrix, rich in collagen. This biomimetic bone‐on‐a‐chip platform can contribute to a better understanding of the processes related to bone formation and remodeling, which in turn can be used for the development of bone regeneration strategies.

Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies

“…To date, few bone-on-chip studies have been conducted, but more research efforts and clinical trials are needed for specific bone marrow diseases such as MM [ 166 , 167 , 168 ]. Because bone is a highly vascularized tissue, it is important to mimic the osteogenic microenvironment.…”

Bone-on-a-Chip: Biomimetic Models Based on Microfluidic Technologies for Biomedical Applications

“…HA absorbs calcium ions and releases phosphate ions. This property alters the composition of the medium, resulting in poor cell survival in in vitro models . To overcome this limitation, Atif et al introduced the dynamic flow of the medium enabling ionic exchange between HA and the medium to study the cell responses under the different flow rates …”

“…To recreate these structural properties of bone tissues in BOC, natural bone-tissue-based scaffolds have been used. Galván-Chacón et al generated a microscale 3D biomimetic bone scaffold, and the developed human trabecular bone model was 3D-imaged using nanocomputerized tomography (CT) . As shown in the nano-CT image and two-photon polymerization (2PP) lithography technology with high resolution, the printed 3D bone model retained the trabeculaelike structure with interconnected pores.…”

Bioengineering Bone‐on‐a‐Chip Model Harnessing Osteoblastic and Osteoclastic Resolution

“…[5] Nevertheless, a functional model does not necessarily encompass the full complexity of the targeted tissue but rather contains a unit that can recapitulate the physiological processes. [6] The intrinsic significance of OoCs is to establish a dynamic microenvironment via mechanotransducive stimulation of hosted cells assisting to obtain their desired phenotype and functionality. [7] Ceramic biomaterials have superiority in substituting the calcified bone matrix due to their osteoconductive, osteoinductive, and ease in forming interconnected porous networks.…”

“…[29] Recent bone-on-a-chip models were reported for studying bone marrow (BM), bone cancer metastasis, bone vascular niche, and hematopoiesis. [6,[30][31][32][33][34][35][36][37][38] Although these studies provide valuable insight into bone-related mechanisms in vitro, dynamic bone remodeling aspects are oversighted. Therefore, there is a need to establish osteogenic niche models where bone turnover can be explored in a native-like mineralized dynamic microenvironment.…”