title: Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids.
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, (1)H-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.
authors.affiliation: a Department of Bioengineering and Temple Institute for Regenerative Medicine and Engineering , Temple University , Philadelphia , PA 19122 , USA.
authors.forename: Shimon
authors.initials: S
authors.lastname: Lecht
authors.forename: Naomi
authors.initials: N
authors.lastname: Cohen-Arazi
authors.forename: Gadi
authors.initials: G
authors.lastname: Cohen
authors.forename: Keren
authors.initials: K
authors.lastname: Ettinger
authors.forename: Tatjana
authors.initials: T
authors.lastname: Momic
authors.forename: Michal
authors.initials: M
authors.lastname: Kolitz
authors.forename: Majdi
authors.initials: M
authors.lastname: Naamneh
authors.forename: Jehoshua
authors.initials: J
authors.lastname: Katzhendler
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lelkes
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000596:Amino Acids; D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D011091:Polyesters; D011108:Polymers; D020932:Nerve Growth Factor