Peptide and peptide-carbon nanotube hydrogels as scaffolds for tissue & 3D tumor engineering

Abstract

For the first time we used hybrid self-assembling peptide-carbon nanotube hybrid hydrogels (that we have recently introduced briefly in the "Carbon" journal in 2014) for tissue engineering and 3D tumor engineering. We showed the potential of these hybrid hydrogels to enhance the efficiency of the peptide hydrogels for tissue engineering application in terms of cell behavior (cell attachment, spreading and migration). This opens up new rooms for the peptide hydrogels and can expand their applications. Also our system (peptide and peptide-CNT hydrogels) was used for cancer cell spheroid formation showing the effect of both tumor microenvironment stiffness and cell-scaffold adhesion on cancer cell invasion. This was only possible based on the presence of CNTs in the hydrogel while the stiffness kept constant. Finally it should be noted that these hybrid hydrogels expand applications of peptide hydrogels through enhancing their capabilities and/or adding new properties to them.

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

“…[ 104 ] In peptide sequence, EFK8 peptide nanofibers have better mechanical strength in hydrogel due to stronger hydrophobic interaction of phenylalanine residues, so that EFK16‐II and EFK8 peptides can disperse carbon nanotubes. [ 105 ] Guilbaud and co‐workers exploit the reverse hydrolytic properties of some enzymes to synthesize self‐assembling peptide hydrogels from a shorter nonself‐assembling peptide precursors. [ 106 ] They find that the long peptide sequences favor the heterogeneous nanofiber networks in hydrogels, which shows that nanofiber network topology at the micrometer scale directly affects the biophysical properties of these hydrogels.…”

“…EFK8 peptide hydrogel has the tunable compressive modulus that is similar with human lung tissue (<1 kPa) when A549 lung cancer cell spheroid formation in vitro is studied. [ 105 ] Some A549 cancer cells at the border of tumor spheroids have the stretched morphology and contain less concentrated β‐catenin on the edges and do not have sharp polygonal boundary, which suggests that A549 cells are able to move more easily over the surface. The functionalized EFK‐RGD peptide hydrogel independently controls the matrix stiffness and cell binding site concentration to influence cell spreading and differentiation within the nanofibrous 3D hydrogel matrix.…”

“…The hybrid self‐assembling peptide (EFK8)‐carbon nanotube (SWNT) hydrogels are designed to observe A549 lung cancer cell morphology from spheroidal to a stretched alteration similar to migratory phenotype in malignant solid tumors (Figure 6C). [ 105 ] A thin layer of RADA16‐I peptide hydrogel may support a miniature ovarian cancer cell pattern for drug chemosensitivity detection when seeded with low ovarian cancer cell density. [ 198 ] So far, by tumor spheroid culture in 3D context, the clonal diversity, cell adaptation, drug repositioning, and malignant phenotype reversion are envisioned in various designer peptide hydrogels described above.…”

Fabrication of a novel hierarchical fibrous scaffold for breast cancer cell culture

“…Such in vitro cancer models have been proven effective in studying cancer pathogenesis and development, anti-cancer mechanism, and drug testing [1][2][3][4]. So far, numerous materials including gelatin, carbon nanotube, collagen, fibrin, poly(lactic acid), poly(glycolic acid), poly(lactic-coglycolic acid), poly (ε-caprolactone), and others have been used to construct in vitro cancer models [5][6][7]. In our previous studies, bacterial cellulose (BC) was also used in light of its 3D network structure and, in particular, its nano-scaled fiber diameter which is the lower limit of natural ECM fibers [8,9].…”

Effect of Functionalized Carbon Nanotubes and their Citric Acid Polymerization on Mesenchymal Stem Cells In Vitro

“…Although in cell therapy, mesenchymal stem cells (MSCs) cultured on scaffolding are a real option in the field of tissue engineering [33] for generate or repair of new tissue [8,9,34,35], one of the major limitations is still the lack of anchoring between the damaged tissue and the cells that are supplied, because the MSCs applied by suspension directly in damaged areas produce little or null improvements on the surrounding damaged tissue [36] by transdifferentiation effect. Thus, the production of adequate scaffolds for proliferation and anchorage of MSCs is a fundamental aspect for future investigation [37] Despite that polymerized CNTs with other materials have effects on the MSC behavior, promoting adhesion [18,[38][39][40], changing stem cell's shape [7,8,41,42], and providing signals that may promote proliferation or differentiation [18], it is unknown if polymerized CNTs with PCA could help as intermediaries or structurally could act as a kind of staple between the extracellular matrix of a damaged tissue with the extracellular matrix of MSCs previously treated in vitro with PMWNT before injected. However, based on the reports of cytotoxic effects of fCNTs [11,14,15,19,25] and polymerized CNTs (PCNT), with PEG, PU, and PET [19,25], prior to considering PMWCNT as biological scaffolding for MSCs, it is mandatory and fundamental to start by performing cytotoxic assays of cells in contact with fCNTs and fPCA-CNTs.…”