3D Synthetic Peptide-based Architectures for the Engineering of the Enteric Nervous System

Brun, Paola; Zamuner, Annj; Peretti, Alessandro; Conti, John A.; Messina, Grazia M. L.; Marletta, Giovanni; Dettin, Monica

doi:10.1038/s41598-019-42071-7

Cited by 26 publications

(31 citation statements)

References 44 publications

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“…[ 98 ] To build precise cell microenvironments for specific cell types, EAK16‐II peptide is conjugated by RGD motif, (GRGDSP) 4 K (fibronectin), FRHRNRKGY (h‐vitronectin), IKVAV (laminin), and type 1 insulin‐like growth factor (IGF‐1), respectively. [ 99 ] As compared with superficial addition in hydrogel, the conjugation of bioactive motifs with EAK16‐II peptide provides the decoration of the whole hydrogel volume rather than only hydrogel surface. These bioengineering hydrogels support the exchange of bioactive factors, oxygen, nutrients, and waste products between cells and their microenvironment.…”

Section: Diverse Self‐assembling Peptide Hydrogels and Their Applicatmentioning

confidence: 99%

“…[ 218 ] E) Functionalized EAK16‐II hydrogels offer the tools to inject or dab the tissue‐specific cell construct onto intestinal areas affected by loss of loconeurons to treat the gastrointestinal disorders caused by the lack of specific neuronal subpopulations. [ 99 ] F) The hNSC‐seeded cell construct in (LDLK) 3 hydrogel provides three translational possibilities in synthetic designer peptide scaffolds, GMP‐hNSCs, and serum‐free cultures in nanotechnology. [ 67 ] G) Instantly produced PuraMatrix hydrogel‐MSC complex is an advanced cell construct for innovative therapy in rat heart failure models, [ 85 ] since the feasibility and efficacy of Purastat hydrogel achieves the clinical approval in suture line hemostasis.…”

Section: Instructive Cell Constructs In Tissue Engineering and Precismentioning

confidence: 99%

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Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such Designer self-assembling peptides form the entangled nanofiber networks in hydrogels by ionic-complementary self-assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue-specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self-assembling peptide hydrogels for instructive cell constructs in tissue-specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.

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Section: Diverse Self‐assembling Peptide Hydrogels and Their Applicatmentioning

confidence: 99%

Section: Instructive Cell Constructs In Tissue Engineering and Precismentioning

confidence: 99%

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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“…In contrast, the MDA-MB231 cell line is derived from metastatic ductal breast carcinoma and presents abundant stroma with fibrous consistency [44]. Both HCC1954 and MDA-MB231 breast cancer cell lines were grown in a collagen-free scaffold based on crosslinked and lyophilized matrix components, such as hyaluronic acid and ioniccomplementary self-assembling peptides (SAPs) condensed with the IKVAV (Ile-Lys-Val-Ala-Val) Laminin adhesion motif [45][46][47]. We previously demonstrated that it could reliably reproduce in vivo tissue architecture [48,49].…”

Section: Morphology Of Hcc1954 and Mda-mb231 3d Cell Culturesmentioning

confidence: 99%

The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

Sieni

Dettin

Robertis

et al. 2020

Cancers

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Gene Electro-Transfer (GET) is a powerful method of DNA delivery with great potential for medical applications. Although GET has been extensively studied in vitro and in vivo, the optimal parameters remain controversial. 2D cell cultures have been widely used to investigate GET protocols, but have intrinsic limitations, whereas 3D cultures may represent a more reliable model thanks to the capacity of reproducing the tumor architecture. Here we applied two GET protocols, using a plate or linear electrode, on 3D-cultured HCC1954 and MDA-MB231 breast cancer cell lines grown on a novel collagen-free 3D scaffold and compared results with conventional 2D cultures. To evaluate the electrotransfer efficiency, we used the plasmid pEGFP-C3 encoding the enhanced green fluorescent protein (EGFP) reporter gene. The novel 3D scaffold promoted extracellular matrix deposition, which particularly influences cell behavior in both in vitro cell cultures and in vivo tumor tissue. While the transfection efficiency was similar in the 2D-cultures, we observed significant differences in the 3D-model. The transfection efficiency in the 3D vs 2D model was 44% versus 15% (p < 0.01) and 24% versus 17% (p < 0.01) in HCC1954 and MDA-MB231 cell cultures, respectively. These findings suggest that the novel 3D scaffold allows reproducing, at least partially, the peculiar morphology of the original tumor tissues, thus allowing us to detect meaningful differences between the two cell lines. Following GET with plate electrodes, cell viability was higher in 3D-cultured HCC1954 (66%) and MDA-MB231 (96%) cell lines compared to their 2D counterpart (53% and 63%, respectively, p < 0.001). Based on these results, we propose the novel 3D scaffold as a reliable support for the preparation of cell cultures in GET studies. It may increase the reliability of in vitro assays and allow the optimization of GET parameters of in vivo protocols.

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“…In this study, we present a new collagen-free 3D scaffold for cell culture aimed at reproducing as close as possible the tissue organization commonly found in tumors in vivo [30,31]. The new scaffold is a crosslinked and lyophilized matrix based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs) condensed with the IKVAV (Ile-Lys-Val-Ala-Val) Laminin adhesion motif [32,33,34]. The proposed collagen-free scaffold promotes HCC1569 and MDA-MB231 growth and induces cellular production of ECM.…”

Section: Introductionmentioning

confidence: 99%

A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy

Dettin

Sieni

Zamuner

et al. 2019

Cells

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Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell–cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell–cell and cell–ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

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3D Synthetic Peptide-based Architectures for the Engineering of the Enteric Nervous System

Cited by 26 publications

References 44 publications

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy

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