A bone‐on‐a‐chip collagen hydrogel‐based model using pre‐differentiated adipose‐derived stem cells for personalized bone tissue engineering

Abstract

Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Adipose‐derived stem cells (ADSC) possess many advantages compared to other origins including easy tissue harvesting, self‐renewal potential, and fast population doubling time. As multipotent cells, they can differentiate into osteoblastic cell linages. In vitro bone models are needed to carry out an initial safety assessment in the study of novel bone regeneration therapies. We hypothesized that 3D bone‐on‐a‐chip models containing ADSC could closely recreate the physiological bone microenvironment and promote differentiation. They represent an intermedium step between traditional 2D–in vitro and in vivo experiments facilitating the screening of therapeutic molecules while saving resources. Herein, we have differentiated ADSC for 7 and 14 days and used them to fabricate in vitro bone models by embedding the pre‐differentiated cells in a 3D collagen matrix placed in a microfluidic chip. Osteogenic markers such as alkaline phosphatase activity, calcium mineralization, changes on cell morphology, and expression of specific proteins (bone sialoprotein 2, dentin matrix acidic phosphoprotein‐1, and osteocalcin) were evaluated to determine cell differentiation potential and evolution. This is the first miniaturized 3D‐in vitro bone model created from pre‐differentiated ADSC embedded in a hydrogel collagen matrix which could be used for personalized bone tissue engineering.

Collagen-Laponite Nanoclay Hydrogels for Tumor Spheroid Growth

“…For instance, to promote osteogenic differentiation of mesenchymal stem cells in vitro , it has been reported that human bone marrow stem cells seeded onto surfaces coated with air-dried Laponite films (2.5 mg/mL) possess a higher osteogenic capacity at week 3 . The supplemented collagen hydrogel reported here could be used to promote osteogenic differentiation of stem cells in a 3D matrix . Furthermore, the tumoral environment has been widely reported to be mechanically stiffer than healthy tissue, particularly in solid tumors.…”

“… 21 The supplemented collagen hydrogel reported here could be used to promote osteogenic differentiation of stem cells in a 3D matrix. 37 Furthermore, the tumoral environment has been widely reported to be mechanically stiffer than healthy tissue, 38 particularly in solid tumors. Therefore, given the mechanical characteristics of the tumoral microenvironment, the collagen-based hydrogel developed in this study may be a suitable tool for cancer research.…”

Synergy between 3D-extruded electroconductive scaffolds and electrical stimulation to improve bone tissue engineering strategies

“…This observation is in accordance with previous studies reporting decreased ALP activities at day 21 in comparison to earlier time points. 107,108 Moreover, during the initial phases of the osteogenesis process, the mechanisms that regulate the ALP activity are highly complex comprising several interlaced signaling pathways ( e.g. Wnt, FGF, and BMP2), the details of which are still poorly understood.…”

Investigation of Soft Matter Nanomechanics by Atomic Force Microscopy and Optical Tweezers: A Comprehensive Review

“…The comprehension of soft matter systems is crucial since they have high potentiality for practical applications. Versatile soft matter could act as core actor to develop key future technologies including electronics [ 199 ], water purification membranes [ 200 ], tissue engineering [ 201 ], artificial intelligence robots [ 202 ] or the design of efficient therapies against human diseases [ 203 ]. For this reason, the knowledge of their intrinsic properties can significantly aid to predict their performance under certain conditions of interest.…”