Novel Agmatine-Containing Poly(amidoamine) Hydrogels as Scaffolds for Tissue Engineering

Abstract

Novel biocompatible and biodegradable amphoteric poly(amidoamine) (PAA) hydrogels were designed for applications as scaffolds for tissue engineering. These hydrogels (PAA-AG1 and PAA-AG2) were obtained by polyaddition of 2,2-bisacrylamidoacetic acid with 2-methylpiperazine and 4-aminobutyl guanidine, a bioactive molecule with a known ability to induce adhesion to cell membranes. They contain carboxylic functions in their main chain and interchain connections deriving from two different cross-linking agents: for PAA-AG1, a multifunctional primary amine, that is, 1,10-decanediamine; for PAA-AG2, a purposely synthesized PAA (PAA-NH(2)) containing pendant NH(2). Both PAA-AG1 and PAA-AG2 proved noncytotoxic and adhesive to cell membranes, as ascertained by means of cytotoxicity and proliferation tests carried out on fibroblast cell lines. Good apparent mechanical strength was also observed in the case of PAA-AG2, cross-linked with the PAA-NH(2). Both PAA-AG1 and PAA-AG2 underwent degradation tests under controlled conditions simulating the biological environments, that is, Dulbecco medium at pH 7.4 and 37 degrees C. They completely dissolved within 10 and about 40 days, respectively. In both cases, the degradation products were completely noncytotoxic. All the results of this paper point to the conclusion that agmatine-based PAA hydrogels are excellent substrates for cell proliferation.

Prevailingly Cationic Agmatine-Based Amphoteric Polyamidoamine as a Nontoxic, Nonhemolytic, and “Stealthlike” DNA Complexing Agent and Transfection Promoter

“…Remember, however, that AGMA1 is ultimately bioeliminable because it degrades in aqueous media to nontoxic products. 13,14 DNA Complexing Ability of AGMA1 and Transfection Experiments. Not surprisingly, owing to its polycationic character, AGMA1 forms stable complexes with DNA in the entire pH range considered (4.0-7.4).…”

Approaches to Biomaterials Testing According to Modern Biocompatibility Paradigm

“…Принято считать, что цитотоксичность, опреде-ляемая как свойство химических веществ оказы-вать токсическое действие на клетки, затрагивает различные аспекты клеточной функции, такие как жизнеспособность, пролиферация, адгезия, био-синтетическая активность и морфология клетки. Изучение данных характеристик при культивиро-вании клеток in vitro позволяет проводить оценку токсикологических рисков использования тестиру-емого материала [20].…”

“…Естественно, в зависимости от природы и функции материалов, адгезия клеток на поверх-ности может быть и нежелательным эффектом. В любом случае, клеточная адгезия является пред-посылкой для оценки любых дальнейших клеточ-ных функций, таких как экспансия, пролиферация, миграция и биосинтетическая деятельность [20].…”

“…Панель методов оценки мутагенности материалов представ- Cell, tissue, and gene therapy лена в стандарте ISO 10993-3 [38, 39] и приведена в таблице [1]. Принципиально тесты на мутагенность заключа-ются в следующем: материал или исследуемый агент контактируют с клетками в течение определенного промежутка времени, после которого оценивают-ся различные, связанные с генами характеристики, в сравнении с положительным (известные геноток-сичные агенты) и отрицательным контролями [20]. In vitro тесты могут быть классифицированы по исполь-зованию прокариотических и эукариотических орга-низмов.…”

Polyamidoamine Nanoparticles as Nanocarriers for the Drug Delivery to Malaria Parasite Stages in the Mosquito Vector

“…PAAs exhibit relatively large hydrodynamic volumes in solution if compared with vinyl polymers of similar mass, indicating a tendency to assume extended chain conformations in solution [34]. By introducing multifunctional amines in the polymerization mixture crosslinked structures can be obtained, which usually absorb large amounts of water and form hydrogels in aqueous media [37]. These hydrogels have been proven to possess good mechanic properties, biocompatibility, biodegradability and ability to induce cell adhesion and proliferation [38].…”