RGD-mimetic poly(amidoamine) hydrogel for the fabrication of complex cell-laden micro constructs.
The potential of the 3D cell culture approach for creating in vitro models for drug screening and cellular studies, has led to the development of hydrogels that are able to mimic the in vivo 3D cellular milieu. To this aim, synthetic polymer-based hydrogels, with which it is possible to fine-tune the chemical and biophysical properties of the cell microenvironment, are becoming more and more acclaimed. Of all synthetic materials, poly(amidoamine)s (PAAs) hydrogels are known to have promising properties. In particular, PAAs hydrogels containing the 2,2-bisacrylamidoacetic acid-agmatine monomeric unit are capable of enhancing cellular adhesion by interacting with the RGD-binding αVβ3 integrin. The synthesis of a new photocrosslinkable, biomimetic PAA-Jeffamine®-PAA triblock copolymer (PJP) hydrogel is reported in this paper with the aim of improving the optical, biocompatibility and cell-adhesion properties of previously studied PAA hydrogels and providing an inexpensive alternative to the RGD peptide based hydrogels. The physicochemical properties of PJP hydrogels are extensively discussed and the behavior of 2D and 3D cell cultures was analyzed in depth with different cell types. Moreover, cell-laden PJP hydrogels were patterned with perfusable microchannels and seeded with endothelial cells, in order to investigate the possibility of using PJP hydrogels for fabricating cell laden tissue-like micro constructs and microfluidic devices. Overall the data obtained suggest that PJP could ultimately become a useful tool for fabricating improved in vitro models in order to potentially enhance the effectiveness of drug screening and clinical treatments.
SEMM, European School of Molecular Medicine, Campus IFOM-IEO, Via Adamello 16, 20139 Milano, Italy.
Alessandro
A
Tocchio
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
Federico
F
Martello
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
Margherita
M
Tamplenizza
SEMM, European School of Molecular Medicine, Campus IFOM-IEO, Via Adamello 16, 20139 Milano, Italy.
Eleonora
E
Rossi
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
Irini
I
Gerges
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milano, Italy.
Paolo
P
Milani
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milano, Italy. Electronic address: Cristina.Lenardi@unimi.it.
Cristina
C
Lenardi
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D051379:Mice; D044085:Microfluidics; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000494:pharmacology*; D055620:Optical Phenomena; D011073:Polyamines / Q000494:pharmacology*
D009842:Oligopeptides; C531249:Poly(amidoamine); D011073:Polyamines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid
3D cell culture; Hydrogel; Poly(amidoamine); RGD mimetic