Bisphosphonate‐functionalized poly(β‐amino ester) network polymers

Abstract

Three novel bisphosphonate-functionalized secondary diamines are synthesized and incorporated into poly(β-amino ester)s (PBAEs) to investigate the effects of bisphosphonates on biodegradation and toxicity of PBAE polymer networks. These three novel amines, BPA1, BPA2, and BPA3, were prepared from the reactions of 1,4-butanediamine, 1,6-hexanediamine, or 4,9-dioxa-1,12-dodecanediamine with tetraethyl vinylidene bisphosphonate, respectively. The PBAE macromers were obtained from the aza-Michael addition reaction of these amines to 1,6-hexane diol diacrylate (HDDA) and poly(ethylene glycol) diacrylate (PEGDA, M = 575) and photopolymerized to produce biodegradable gels. These gels with different chemistries exhibited similar degradation behavior with mass loss of 53-73% within 24 h, indicating that degradation is mostly governed by the bisphosphonate group. Based on the in vitro cytotoxicity evaluation against NIH 3T3 mouse embryonic fibroblast cells, the degradation products do not exhibit significant toxicity in most cases. It was also shown that PBAE macromers can be used as cross-linkers for the synthesis of 2-hydroxyethyl methacrylate hydrogels, conferring small and customizable degradation rates upon them. The materials reported have potential to be used as nontoxic degradable biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1412-1421, 2017.

Urea dimethacrylates functionalized with bisphosphonate/bisphosphonic acid for improved dental materials

“…Two secondary amines (BPA1 and BPA2) for the synthesis of monomers were prepared from the reaction of 1,4‐butanediamine and 1,6‐hexanediamine with tetraethyl ethenylidenebis(phosphonate) in DMF at room temperature for 2 days . The amines were subsequently treated with IEM at room temperature in dry chloroform to give the target trisubstituted urea dimethacrylates 1a as a viscous liquid in 50–60% yield and 1b as a white solid with a melting point of 99 °C in 55% yield (Fig.…”

“…Tetraethyl ethenylidenebis(phosphonate) was prepared from tetraethyl methyl bisphosphonate by the method reported by Degenhardt and Burdsall . Two bisphosphonate‐functionalized amines (BPA1 and BPA2) were synthesized as reported by us for the first time . Tetraethyl methyl bisphosphonate, IEM, 2‐hydroxyethyl methacrylate (HEMA), TEGDMA, Bis‐GMA, 2,2′‐dimethoxy‐2‐phenyl acetophenone (DMPA), camphorquinone (CQ), phenylbis (2,4,6‐trimethylbenzoyl)‐phosphine oxide (BAPO), and all other reagents and solvents were obtained from Aldrich Chemical Co. and used as received without further purification.…”

Buffering effects on the solution behavior and hydrolytic degradation of poly(β‐amino ester)s

“…Given that PBAEs are frequently employed in the networked state 13,15,24,26,34–36 and in solution at concentrations where the polymer amines exceed the concentration of buffer, it is important to understand the pH‐dependent behavior of PBAEs to predict and program PBAE degradation. For example, 1X phosphate buffered saline (PBS) contains mostly sodium chloride with only 10 m M phosphate buffer, and therefore, PBAE amine concentrations exceeding 10 mM are likely to render the buffer ineffective.…”

Structure-property relationships of novel phosphonate-functionalized networks and gels of poly(β-amino esters)

“…Incorporation of phosphorous containing groups to polymeric networks extends their application areas due to their strong interaction with hydroxyapatite-based tissue [36][37][38][39] and enhances their cell adhesion, [40][41][42][43][44][45] swelling and thermal properties. Recently, we have reported the effect of the phosphonate and bisphosphonate group on PBAE network properties [46][47][48]. Phosphonate-functionalized PBAE macromers were synthesized through reaction of various diacrylates and a primary phosphonate-functionalized amine (diethyl 2-aminoethylphosphonate).…”