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

Abstract

Incorporation of bisphosphonate/bisphosphonic acid groups in dental monomer structures should increase interaction of these monomers with dental tissue as these groups have strong affinity for hydroxyapatite. Therefore, new urea dimethacrylates functionalized with bisphosphonate (1a, 1b) and bisphosphonic acid (2a, 2b) groups are synthesized and evaluated for dental applications. Monomers 1a and 1b are synthesized from 2isocyanatoethyl methacrylate (IEM) and two bisphosphonated amines (BPA1 and BPA2), prepared as reported elsewhere. Selective dealkylation of the bisphosphonate ester groups of 1a and 1b using trimethylsilyl bromide (TMSBr) gives monomers (2a and 2b) with bisphosphonic acid functionality. X-ray diffractometer (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) analyses of monomer-treated HAP particles show that 2a induces formation of stable monomer-calcium salts, similar to 10methacryloyloxydecyl dihydrogen phosphate (MDP), with higher chemical interaction than 2b. The photopolymerization studies indicate good copolymerizability with commercial dental monomers. In vitro studies on NIH 3T3 mouse embryonic fibroblast cells have clearly shown that the tested monomers (1b and 2b) are not toxic according to the MTT standards. All these properties make these monomers suitable as biocompatible cross-linkers/adhesives for dental applications.

Bisphosphonic Acid-Functionalized Cross-Linkers to Tailor Hydrogel Properties for Biomedical Applications

“…The solution was concentrated under reduced pressure to give pure products. 1a gives monomer 2a, reported previously by us, 38 and 1b gives novel monomer 2b, obtained as a yellow waxy solid in 75% yield. Solubilities of 2a and 2b together with 1a and 1b are given in Table S1.…”

“…Monomers (2a, 2b) were synthesized by the reaction of two bisphosphonated amines (BPA1 and BPA2) with 2-isocyanatoethyl methacrylate (IEM) to form BP-containing monomers (1a, 1b), followed by the dealkylation of the BP groups by trimethylsilyl bromide (TMSBr) (Figure 1). Synthesis of 1a and 2a as well as their starting amine BPA1 was reported earlier by us; 38,39 however, 1b and 2b are novel. The acidic monomers (2a, 2b) were obtained as white colored waxy solids in 52−75% yields.…”

“…In our previous work, urea dimethacrylates functionalized with BP and bisphosphonic acid groups were synthesized and evaluated for dental applications. 38 The general structure of these monomers allows choice of different spacer chains between the double bonds, which will naturally modify their various properties.…”

“…Nanocomposite hydrogels based on reversible bonds between calcium phosphate nanoparticles or bioactive glass and BP-functionalized HA or gelatin display self-healing as well as adhesiveness to mineral surfaces such as HAP and show potential in bone-tissue engineering. − Incorporation of bisphosphonic acid groups in dental monomer structures increases their interaction with dental tissues. In our previous work, urea dimethacrylates functionalized with BP and bisphosphonic acid groups were synthesized and evaluated for dental applications . The general structure of these monomers allows choice of different spacer chains between the double bonds, which will naturally modify their various properties.…”

Enhanced Osteogenic Potential of Phosphonated-Siloxane Hydrogel Scaffolds

“…When incorporated into scaffolds, tethered small molecules have been shown to enhance osteogenic potential via local changes to the chemical environment that impact cellular behavior. ,,, Such small molecules showing strong indications for osteogenesis and mineralization, by a variety of mechanisms, include amines, alcohols, and phosphates/phosphonates. ,− Specifically, phosphorus-containing groups have shown promise because of their native roles in calcium binding and mineralization in bone tissue formation . Phosphonate-based chemistries have been independently explored with hydrogels, composites, ceramics, and metal implants and shown to promote bone tissue regeneration. ,− …”