Capturing Essential Physiological Aspects of Interacting Cartilage and Bone Tissue with Osteoarthritis Pathophysiology: A Human Osteochondral Unit‐on‐a‐Chip Model

Abstract

Given the multi‐tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires appropriate human in vitro OA models that incorporate both functional bone and cartilage tissue units. Therefore, a microfluidic chip is developed with an integrated fibrous polycaprolactone matrix in which neo‐bone and cartilage are produced, that could serve as a tailored human in vitro disease model of the osteochondral unit of joints. The model enables to evaluate OA‐related environmental perturbations to (individual) tissue units by controlling environmental cues, for example by adding biochemical agents. After establishing the co‐culture in the system, a layer of cartilaginous matrix is deposited in the chondrogenic compartment, while a bone‐like matrix is deposited between the fibers, indicated by both histology and gene expression levels of collagen type 2 and osteopontin, respectively. As proof‐of‐principle, the bone and cartilaginous tissue are exposed to active thyroid hormone, creating an OA disease model. This results in increased expression levels of hypertrophy markers integrin‐binding sialoprotein and alkaline phosphatase in both cartilage and bone, as expected. Altogether, this model could contribute to enhanced translation from OA risk genes towards novel OA therapies.

Progress of Microfluidic Hydrogel‐Based Scaffolds and Organ‐on‐Chips for the Cartilage Tissue Engineering

“…B) I) Reproduced with permission. [ 264 ] Copyright 2022, The Authors, published by Wiley‐VCH. C) I) Electrospun nanofiber scaffold.…”

“…As a result, using another cell source like iPSCs for this model can be favorable. [264] In one of the most recent studies, Li and co-workers [390] addressed the limitation associated with the absence of some joint tissues, namely adipose and synovium tissues, in the OA models by designing an OoC platform, referred to as miniJoint, that incorporated synovial-like fibrous tissue, OC complex, and adipose tissue. In brief, hBMSCs (20 × 10 6 cells mL −1 for all except fibroblasts) were suspended in 15% w/v GelMA and the resultant suspensions were pipetted in the microfluidic-based bioreactor's inserts, followed by photo-cross-linking with UV light.…”

“…It is possible to employ this simple and inexpensive approach with a wide range of polymers. Nevertheless, since the used polymer must be in the solution form, some toxic organic solvents are [264] Copyright 2022, The Authors, published by Wiley-VCH. C) I) Electrospun nanofiber scaffold.…”

“…introduced to the complex, thus negatively affecting the fibers' cytocompatibility. [252,[259][260][261][262][263] Recently, Tuerlings et al [264] designed a dual-tissue microfluidic device as a biomimetic model to study the OA disease (Figure 10B). In this regard, they first produced PCL nanofibers and microfibers using an electrospinning machine and then placed them within a molded PDMS chip consisting of a chondrogenic channel and an osteogenic channel in order to separate the channels via the electrospun PCL fibers.…”

“…B) The hypertrophy markers' gene expressions in: I) the chondrogenic chamber and II) the osteogenic chamber after the addition of triiodothyronine hormone (*p < 0.05). A,B) Reproduced with permission [264]. Copyright 2022, The Authors, published by Wiley-VCH.…”