Cellular interactions with biodegradable polyurethanes formulated from L-tyrosine

Abstract

L-Tyrosine polyurethanes (LTUs) have been synthesized by structural modification of the poly (amino acid) backbone to circumvent the problems associated with the processing of poly (amino acids) arising from their high crystallinity, insolubility in common organic solvents, and high glass-transition and melting temperatures. Additionally, problems such as unpredictable swelling characteristics, change in conformation, and uncontrolled enzymatic degradation have severely restricted the use of poly (amino acids). In contrast, LTUs are designed to retain their superior physico-chemical properties, while incorporating biodegradability through enzymatic, hydrolytic, and oxidative pathways. The aim of this study is to evaluate initially the biocompatibility of LTUs and their degradation products. Studies involving primary dermal human fibroblasts cultured in contact with LTU films or degradation products suggest a lack of toxicity (cell viabilities >93% with p < 0.05 compared to the control for all studies). The diversity of LTU polymer chemistry and the ability of LTUs to phase separate seem to present a heterogeneous surface with variable wettability. This phenomenon influences the adhesion and proliferation of human fibroblasts on polymeric surfaces, wherein fibroblast adhesion on polycaprolactone diol (PCL) based LTUs is characterized by higher cell counts (81,250 ± 18,390 for PCL-C-DTH (desaminotyrosine-tyrosyl hexyl, DTH), 58,360 ± 7370 for PCL-L-DTH, 38,480 ± 12,680 for PEG-C-DTH (polyethylene glycol, PEG), and 46,430 ± 16,000 for PEG-L-DTH at 120 h with p < 0.001 for comparison between PCL-C-DTH and all other LTUs), more rapid cellular proliferation (doubling time of 37-49 h for PCL-based LTUs compared to 68-90 h for PEG-based LTUs), and a uniform cell distribution compared to PEG-based LTUs. However, immunofluorescence assay for F-actin suggests that the cells are well attached. Thus, the lack of cytotoxicity and the ability to control cellular adhesion through polymer chemistry make LTUs attractive candidates for tissue-engineering applications that require elastomeric, biodegradable, and biocompatible polymers.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

“…Incorporation of peptides into a PU backbone can endow the PU with improved biocompatibility and biodegradability, and create a specific biological function, such as enzyme liability or enhanced cell attachment [ 67 , [139] , [140] , [141] , [142] , [143] , [144] ]. A YIGSR peptide as a chain extender was introduced into a PU backbone to enhance the endothelialization of the PU as a small-diameter vascular graft [ 139 ].…”

“…A YIGSR peptide as a chain extender was introduced into a PU backbone to enhance the endothelialization of the PU as a small-diameter vascular graft [ 139 ]. l -tyrosine-based and lysine-based chain extenders have been introduced into the PU backbone to promote polymer biocompatibility and biodegradability [ 64 , 140 , 141 ]. An Ala-Ala-Lys (AAK) peptide, which can be specifically cleaved by elastase, was used as a chain extender for PU synthesis to improve the polymer's enzymatic degradation ( Fig.…”

MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression

“…In addition, the effect of miR-378a-3p on gli3 is mediated by transcriptional regulation of the nuclear factor-κB (NF-κB) p65 subunit, interacting with Smo. To explore the clinical implications, we encapsulate miR-378a-3p with nanoparticles (NPs) fabricated with L -tyrosine polyurethane (LTU2a), a biodegradable polymer composed of a modified amino acid, PEG and hexamethylene diisocynate in its backbone 13 14 . In-vivo application reduces the expression of Gli3 and matrix markers, and leads to the recovery of fibrosis.…”

Cell–material interactions on biphasic polyurethane matrix

“…PU, including L ‐tyrosine‐based PU, are cytocompatible to different cell line and this study also indicates that polyurethane matrix is nontoxic to MSCs 44. Nanostructured features of synthetic matrices influence cell adhesion and proliferation through different mechanistic pathways.…”

“…PU, including L-tyrosine-based PU, are cytocompatible to different cell line and this study also indicates that polyurethane matrix is nontoxic to MSCs. 44 Nanostructured features of synthetic matrices influence cell adhesion and proliferation through different mechanistic pathways. Particularly, cell adhesion has shown strong dependence on matrix nanostructures, for example, presentation of RGD ligands with defined density and spatial distribution ''turns on'' clustered integrin mediated cell adhesion.…”