Design of Decorated Self-Assembling Peptide Hydrogels as Architecture for Mesenchymal Stem Cells

Abstract

Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D "architecture" for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK) and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP) motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1). The mesenchymal stem cell adhesion assays showed a significant increase in adhesion and proliferation for the hydrogels decorated with each of the synthesized conjugates; moreover, such functionalized 3D hydrogels support cell spreading and elongation, validating the use of this class of self-assembly peptides-based material as very promising 3D model scaffolds for cell cultures, at variance of the less realistic 2D ones. Furthermore, small amplitude oscillatory shear tests showed that the presence of IGF-1-conjugate did not alter significantly the viscoelastic properties of the hydrogels even though differences were observed in the nanoscale structure of the scaffolds obtained by changing their composition, ranging from long, well-defined fibers for conjugates with adhesion sequences to the compact and dense film for the IGF-1-conjugate.

Tuning of hydrogel stiffness using a two‐component peptide system for mammalian cell culture

“…Metabolic activity measured at 24 h post‐seeding was reduced compared to 3 h incubation and the TCP control for all samples. This observation is commonly seen when cells are seeded on hydrogels . After 48 h of incubation the metabolic activity of cells grown on H2, H4, H5 hydrogels was slightly less than the cells grown on TCP.…”

“…This observation is commonly seen when cells are seeded on hydrogels. 6 After 48 h of incubation the metabolic activity of cells grown on H2, H4, H5 hydrogels was slightly less than the cells grown on TCP. However, the metabolic activity of the cells grown on the stiffer hydrogels; H3, H6, and H7, was observed to be similar to those grown on the 2D plastic surface.…”

“…In the last decade, hydrogels formed from self‐assembling peptides were recognized as useful scaffolds for cell culture and tissue regeneration . Self‐assembling peptide hydrogels (SAPHs) are advantageous as they are easy to produce, non‐toxic, biocompatible, biodegradable, often injectable and as such applicable as scaffolds for tissue engineering as well as for drug delivery systems . A number of successful studies have demonstrated the feasibility of using peptide‐based hydrogels as scaffolds for a high number of cell types .…”

“…[1][2][3] Self-assembling peptide hydrogels (SAPHs) are advantageous as they are easy to produce, nontoxic, biocompatible, biodegradable, often injectable and as such applicable as scaffolds for tissue engineering as well as for drug delivery systems. [4][5][6] A number of successful studies have demonstrated the feasibility of using peptide-based hydrogels as scaffolds for a high number of cell types. [7][8][9][10] The main advantages of SAPHs over other types of hydrogels is the absence of harmful chemicals (e.g., toxic cross-linkers) to obtain the hydrogels, high internal hydration and a fibrous peptide nano-architecture, mimicking collagen fibers that offer a valid choice as extracellular matrix (ECM) mimics.…”

New substrates for stem cell control

“…ADSC-loaded hydrogel injection into nude mice resulted in good cell retention and ECM deposition at the injection site 14 days post-transplantion, in contrast with cells injected without gel encapsulation. In a further study, an eight-arm starshaped polyethylene glycol (PEG) was conjugated to one [24] hPSC switch from self-renewal to differentiation collagen [25] MSC chondrogenesis collagen nanovibrational bioreactor [26] MSC osteogenesis collagen-RGD [27] MSC articular cartilage formation elastin with citric acid [28] MSC osteogenesis ELP, ELP-HA [29,30] ADSC, MSC fibrin-IKVAV [31] neural SC differentiation fibronectin-Au [32] MSC endothelialization heparin [33] hPSC expansion hyaluronic acid [34] MSC chondrogenesis laminin 521 and laminin 111 [35] hESC to hepatocyte recombinant protein hydrogels [36 -39] hiPSC-EC, ADSC, peptide Au-SAM with RGD [40] MSC differentiation capacity EAK [41] MSC proliferation…”