Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids

Shimon Lecht, Naomi Cohen-Arazi, Gadi Cohen, Keren Ettinger, Tatjana Momic, Michal Kolitz, Majdi Naamneh, Jehoshua Katzhendler, Abraham J. Domb, Philip Lazarovici, Peter I. Lelkes

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, 1H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.

Original languageEnglish
Pages (from-to)608-624
Number of pages17
JournalJournal of Biomaterials Science, Polymer Edition
Volume25
Issue number6
DOIs
StatePublished - 13 Apr 2014
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by The Israel Science Foundation [grant number 591/08] and the Alex Grass Center for Drug Design and Synthesis of Novel Therapeutics at The Hebrew University.

Funding

This study was supported by The Israel Science Foundation [grant number 591/08] and the Alex Grass Center for Drug Design and Synthesis of Novel Therapeutics at The Hebrew University.

FundersFunder number
Novel Therapeutics
Hebrew University of Jerusalem
Israel Science Foundation591/08

    Keywords

    • adhesion
    • cytocompatibility
    • differentiation
    • endothelial cells
    • neuronal cells
    • proliferation
    • zeta potential
    • α-hydroxy amino acid polyester

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