Phosphonate‐functionalized poly(β‐amino ester) macromers as potential biomaterials

Abstract

Biodegradability, hemocompatibility, resistance to protein adsorption, and strong interactions with hydroxyapatite (HAP)-based tissues such as dentin, enamel, and bone are important properties of phosphorus-containing biomaterials. Here, novel phosphonate-functionalized poly(β-amino ester) (PBAE) macromers are synthesized through aza-Michael addition of various diacrylates [1,6-hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA, M = 575), 1,4-butanediol diacrylate (BDDA), 1,6-hexanediol ethoxylate diacrylate (HDEDA) and triethylene glycol diacrylate (TEGDA)] and a phosphonate-containing primary amine (diethyl 2-aminoethylphosphonate, A1) efficiently without any catalyst; where replacement of A1 with propyl amine (PA) served as control. The macromers, whose molecular weight is ca. 1000-4000 Da as confirmed by both GPC and H-NMR spectroscopy, are photopolymerized to give biodegradable gels. The degradation behavior and cell interaction of these gels are studied. The degradation rates of the gels can be varied by choice of starting acrylates and the acrylate:amine ratio. Furthermore, the gels showed slightly higher degradability than PA-based analogs (controls). Except TEGDA and PEGDA-based ones, all phosphonate-functionalized PBAE gels supported the attachment of larger number of SaOS-2 cells than nonphosphonated ones and the best film was found to be the one based on HDEDA-A1 with balanced hydrophilicity. Degradation products of these films have no significant cytotoxicity except HDDA-PA. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1390-1399, 2018.

One-Step Injectable and Bioreducible Poly(β-Amino Ester) Hydrogels as Controlled Drug Delivery Platforms

“…Therefore, hydrogels have been widely exploited for biomedical applications, such as tissue engineering and delivery of therapeutic agents. , Poly­(β-amino ester)­s (PBAEs) are biodegradable and biocompatible polymers that are synthesized by step-growth polymerization via aza-Michael reaction of diamines and diacrylates . In many studies, PBAEs have been proven to be successful as potential biomaterials for tissue engineering scaffolds, nonviral vectors for gene delivery, and depots for the sustained release of drugs. − Biomedical applications of PBAEs have been reported in a detailed review by Liu et al…”

Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: Case study of an unexpected photopolymer-drug reaction

“…The proton at the position 27 has only three carbon correlations in the HMBC spectrum (Supplementary Figure A) indicating the formation of a secondary amine via the single functionalisation of the primary amine with PEGDA. Akyol et al described the synthesis of novel poly(beta amino ester) macromonomers through Michael addition of various diacrylates including PEGDA and a phosphonate that contains primary amine, as well as propyl amine [41]. In their 1H-NMR spectra, a change of peaks was observed due to methylene groups attaching to a carbonyl group, nitrogen and oxygen.…”

Synthesis and Evaluation of Cytocompatible Alkyne-Containing Poly(β-amino ester)-Based Hydrogels Functionalized via Click Reaction

“…Terminal acrylate groups of PAEs were generally conjugated to many target molecules to enhance the transfection efficacy . Moreover, there are increased interests in PAE applications as a drug delivery system and in regenerative medicine for replacing and/or assisting damaged tissues. − Especially, in situ forming hydrogels based on PAEs became a promising carrier for bioactive molecule delivery and tissue engineering systems due to their convenient preparation and easy filling of the tissue defect by minimal invasive implantation. However, only two terminal acrylate groups make the hydrogel with less cross-linking and weak mechanical properties, and multiple functional modification of PAE is still limited. − …”