Cationic polyelectrolyte hydrogel fosters fibroblast spreading, proliferation, and extracellular matrix production: Implications for tissue engineering.
Fibrous encapsulation is known to occur to many prosthetic implants and is thought to be due to the cells not adhering adequately to the surface. For developing new materials able to enhance cellular adhesion by mimicking extracellular matrix components, polyelectrolyte polymers, characterized by tunable surface charges, have been proposed. Here we demonstrate that panoply of cell functions over a two-dimensional substratum is influenced by surface charge. We have at first generated structurally related polyelectrolyte substrata varying in their positive surface charge amount and subsequently evaluated a variety of behaviors of human primary fibroblasts seeded on these polymers. The proportion of adherent, spreading, and proliferating cells was increased significantly on cationic hydrophilic surfaces when compared with the neutral base surface. The extent of cell spreading correlated with cytoskeleton organization as assessed using immunofluorescence techniques. In the key experiment, the presence of cationic charges on cell adhesion-resistant neutral surface increased the synthesis of collagen I and III, the release of their metabolites, and the expression of their mRNA by fibroblasts. Interestingly, the scarce collagen deposits on neutral polymer consisted, for the most part, of collagen I while collagen III was present only in traces probably due to the secretion of metalloproteinase-2 by non-adherent fibroblasts. Taken together, these results show that polyelectrolyte films may promote the attachment of fibroblast cells as well as their normal secretory phenotype. Both effects could be potentially useful in integrating soft connective tissue to the implant, decreasing the chance of its fibrous encapsulation.
Department of Experimental Medicine, II University of Naples, School of Medicine, Naples, Italy.
Mario
M
De Rosa
Maria
M
Carteni'
Orsolina
O
Petillo
Anna
A
Calarco
Sabrina
S
Margarucci
Francesco
F
Rosso
Alfredo
A
De Rosa
Ernesto
E
Farina
Pasquale
P
Grippo
Gianfranco
G
Peluso
D000328:Adult; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D020100:Hydrogels / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D000071228:Polyelectrolytes; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013499:Surface Properties; D023822:Tissue Engineering; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D003094:Collagen; D020100:Hydrogels; D020782:Matrix Metalloproteinases; D008689:Methacrylates; D009570:Nitriles; D011073:Polyamines; D000071228:Polyelectrolytes; D019714:Tissue Inhibitor of Metalloproteinases; C005044:hydroxyethyl methacrylate; C004526:azobis(isobutyronitrile)