Emerging modulators for osteogenic differentiation: a combination of chemical and topographical cues for bone microenvironment engineering

Jesus, Diana; Pinho, Ana Rita; Gomes, Maria C.; Oliveira, Cláudia S.; Mano, João F.

doi:10.1039/d2sm00009a

Cited by 9 publications

(9 citation statements)

References 86 publications

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“…[ 49 ] This preference could be associated with the similarity of this topography to the fibrillar organization of ECM, particularly collagen fibrils. [ 50 ] In addition, MSC differentiation may explain the plateau in cellular metabolic activity, which may be associated with a late stage of differentiation. [ 51 ] Altogether, these results revealed the potential of these PL microparticles as suitable platforms for cell differentiation in bone‐like cells.…”

Section: Resultsmentioning

confidence: 99%

Self‐Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom‐Up Tissue Engineering

et al. 2023

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There is a demand to design microparticles holding surface topographies while presenting inherent bioactive cues for applications in the biomedical and biotechnological fields. Using the pool of proteins present in human‐derived platelet lysates (PL), it is reported the production of protein‐based microparticles via a simple and cost‐effective method, exploring the prone redox behavior of cysteine (‐SH) amino acid residues. The forced formation of new intermolecular disulfide bonds results in the precipitation of the proteins as spherical, pompon‐like microparticles with adjustable sizes (15‐50 μm in diameter) and surface topography consisting of grooves and ridges. These PL microparticles exhibit extraordinary cytocompatibility, allowing cell‐guided micro‐aggregates to form, while also working as injectable systems for cell support. Early studies also suggests that the surface topography provided by these PL microparticles can support osteogenic behavior. Consequently, these PL microparticles may find use to create live tissues via bottom‐up procedures or injectable tissue‐defect fillers, particularly for bone regeneration, with the prospect of working under xeno‐free conditions.This article is protected by copyright. All rights reserved

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Section: Resultsmentioning

confidence: 99%

Self‐Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom‐Up Tissue Engineering

et al. 2023

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“…[10,48,[62][63][64][65] Biochemical cues can be included using cells growth factors, chemical reagents, cellular proteins, kinases, small molecules, and synthetic materials, [66,67] whereas biomechanical stimulations involve surface properties of substrates, stiffness, roughness, pore size, topography, matrix hardness, external stress and strain, hydrostatic pressure, and electromagnetic field. [67][68][69] Synergistic stimulation of biochemical and biophysical cues leads to more precise simulation of microenvironments in vivo and a broader control over cell behaviors. [67] In one work, it was shown that the combining effect of fluid shear stress and presence of bone-like extracellular matrix synergistically enhanced the osteogenic differentiation of rat MSCs.…”

Section: Evaluation Of Mineralization and Osteogenic Markers Expressionmentioning

confidence: 99%

Viscous Microcapsules as Microbioreactors to Study Mesenchymal Stem/Stromal Cells Osteolineage Commitment

Ghasemzadeh-Hasankolaei

Miranda

Correia

et al. 2023

Small Methods

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It is essential to design a multifunctional well‐controlled platform to transfer mechanical cues to the cells in different magnitudes. This study introduces a platform, a miniaturized bioreactor, which enables to study the effect of shear stress in microsized compartmentalized structures. In this system, the well‐established cell encapsulation system of liquefied capsules (LCs) is used as microbioreactors in which the encapsulated cells are exposed to variable core viscosities to experience different mechanical forces under a 3D dynamic culture. The LC technology is joined with electrospraying to produce such microbioreactors at high rates, thus allowing the application of microcapsules for high‐throughput screening. Using this platform for osteogenic differentiation as an example, shows that microbioreactors with higher core viscosity which produce higher shear stress lead to significantly higher osteogenic characteristics. Moreover, in this system the forces experienced by cells in each LC are simulated by computational modeling. The maximum wall shear stress applied to the cells inside the bioreactor with low, and high core viscosity environment is estimated to be 297 and 1367 mPa, respectively, for the experimental setup employed. This work outlines the potential of LC microbioreactors as a reliable in vitro customizable platform with a wide range of applications.

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“…Previous studies have shown that the osteoconductive behavior of HA in collagen or gelatin-derived scaffolds potentiates cell differentiation. [30,33,34] Our data demonstrate the potential of both systems for autonomously guiding BM-hMSCs differentiation toward an osteogenic lineage, highlighted by the expression of membrane markers associated with osteogenic differentiation (BMP2, Col-I, OPN, and OCN). [30] However, the results also indicated that the GH+GD system underwent a faster differentiation process than the GH system, as observed by evident changes in BM-hMSCs behavior on day 14.…”

Section: Discussionmentioning

confidence: 62%

“…Previous studies have shown that the osteoconductive behavior of HA in collagen or gelatin‐derived scaffolds potentiates cell differentiation. [ 30,33,34 ]…”

Section: Discussionmentioning

confidence: 99%

Bioactive Self‐Regulated Liquified Microcompartments to Bioengineer Bone‐Like Microtissues

Pinho,

Gomes,

Costa

et al. 2023

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Designing a microenvironment that drives autonomous stromal cell differentiation toward osteogenesis while recapitulating the complexity of bone tissue remains challenging. In the current study, bone‐like microtissues are created using electrohydrodynamic atomization to form two distinct liquefied microcapsules (mCAPs): i) hydroxypyridinone (HOPO)‐modified gelatin (GH mCAPs, 7.5% w/v), and ii) HOPO‐modified gelatin and dopamine‐modified gelatin (GH+GD mCAPs, 7.5%+1.5% w/v). The ability of HOPO to coordinate with iron ions at physiological pH allows the formation of a semipermeable micro‐hydrogel shell. In turn, the dopamine affinity for calcium ions sets a bioactive milieu for bone‐like microtissues. After 21 days post encapsulation, GH and GH+GD mCAPs potentiate autonomous osteogenic differentiation of mesenchymal stem cells accompanied by collagen type‐I gene upregulation, increased alkaline phosphatase (ALP) expression, and formation of mineralized extracellular matrix. However, the GH+GD mCAPs show higher levels of osteogenic markers starting on day 14, translating into a more advanced and organized mineralized matrix. The GH+GD system also shows upregulation of the receptor activator of nuclear factor kappa‐B ligand (RANK‐L) gene, enabling the autonomous osteoclastic differentiation of monocytes. These catechol‐based mCAPs offer a promising approach to designing multifunctional and autonomous bone‐like microtissues to study in vitro bone‐related processes at the cell‐tissue interface, angiogenesis, and osteoclastogenesis.

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Emerging modulators for osteogenic differentiation: a combination of chemical and topographical cues for bone microenvironment engineering

Abstract: Bone tissue engineering has primarily aimed to recreate the bone microenvironment by delivering key biomolecules and/or by modification of scaffolds to guide cell fate towards the osteogenic lineage.

Cited by 9 publications

References 86 publications

Self‐Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom‐Up Tissue Engineering

Self‐Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom‐Up Tissue Engineering

Viscous Microcapsules as Microbioreactors to Study Mesenchymal Stem/Stromal Cells Osteolineage Commitment

Bioactive Self‐Regulated Liquified Microcompartments to Bioengineer Bone‐Like Microtissues

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