Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated nanofibres

Bartneck, Matthias; Heffels, Karl-Heinz; Pan, Yu; Bovi, Manfred; Zwadlo-Klarwasser, Gabriele; Groll, Jürgen

doi:10.1016/j.biomaterials.2012.02.050

Cited by 115 publications

(86 citation statements)

References 50 publications

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“…These results indicate that P(TMC-CL) surface features are determinant for microglia shape, but this does not impact long-term cytokine release, suggesting that cell shape is not a parameter on which one can directly predict functional state. A similar issue has been previously raised by Bartneck et al [44] when comparing macrophages cultured on flat spin-coated films and hydrogel-coated nanofibres with variable fibre density (and pore size). The authors claimed that the effect on cell morphology and the expression of surface markers is strongly affected by the biomaterial to which cells adhere.…”

Section: Discussionsupporting

confidence: 56%

The role of the surface on microglia function: implications for central nervous system tissue engineering

Pires

Rocha

Ambrosio

et al. 2015

J. R. Soc. Interface.

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In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia-the resident immune cells of the central nervous system (CNS)-and on their response to poly(trimethylene carbonate-co-1-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-a was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microgliaconditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration.

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Section: Discussionsupporting

confidence: 56%

The role of the surface on microglia function: implications for central nervous system tissue engineering

Pires

Rocha

Ambrosio

et al. 2015

J. R. Soc. Interface.

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“…For this reason, increase in the M2:M1 ratio following implantation of our Nrg-14 containing SCs might suggest that the initial immune reaction to the implant evolved into a more constructive response over time. This would correspond to our observation that PLGA/NCO-sP(EO-stat-PO) ES fibers induce M2 phenotype macrophages in vitro [31]. However, more long-term studies will be needed to analyze the full regenerative potential of this innovative biomaterial in vivo.…”

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confidence: 82%

Polymeric Electrospun Scaffolds: Neuregulin Encapsulation and Biocompatibility Studies in a Model of Myocardial Ischemia

Simón-Yarza

Rossi

Heffels

et al. 2015

Tissue Engineering Part A

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Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell-and/or growth factor-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging growth factor exposure have become fundamental goals in advancing these therapeutic approaches.Biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a PLGA/NCO-sP(EO-stat-PO) polymer blend encapsulating the cardioactive growth factor, Neuregulin-1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg-containing biomaterial in a rat model of myocardial ischemia. Histological analysis revealed the presence of an initial acute inflammatory response after implantation, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, an increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg-encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.

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“…While several previous OA models have employed 2D monolayers, [19][20][21][22][23] the literature reveals that cell behavior in 2D is often not representative of cell responses observed in physiologically relevant 3D contexts. [24][25][26][27] Indeed, an increasing number of studies recently reporting in vitro OA models have cultured chondrocytes within 3D microenvironments. [28][29][30][31][32] However, important auxiliary cell types such as macrophages have continued to be cultured in 2D, 28,31,33 despite the primary location of the macrophages in the knee joint being within the synovial membrane.…”

Section: Introductionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated nanofibres

Cited by 115 publications

References 50 publications

The role of the surface on microglia function: implications for central nervous system tissue engineering

The role of the surface on microglia function: implications for central nervous system tissue engineering

Polymeric Electrospun Scaffolds: Neuregulin Encapsulation and Biocompatibility Studies in a Model of Myocardial Ischemia

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

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