(BIS) phosphonate functionalized polymeric materials for biomedical applications

Abstract

This work describes synthesis, characterization, and evaluation of (bis)phosphonate functionalized monomers, macromers and crosslinkers as well as their polymers and crosslinked networks for biomedical applications such as tissue engineering scaffolds, dental materials and targeted drug delivery. Various synthetic approaches were explored for incorporation of (bis)phosphonate functionality and tailoring of these materials’ properties such as degradation rate, mechanical moduli, mineralization ability, water solubility and hydroxyapatite affinity. In the first part, three novel phosphonate/phosphonic acid functionalized poly (β-amino ester) (PBAE) macromers with varying levels of hydophilicity were synthesized and homo- and copolymerized with poly(ethylene glycol) diacrylate (PEGDA) to fabricate networks with tunable degradation and mechanical properties. The second part reports synthesis of three novel phosphonic acid containing poly (amido amine) macromers and their homo- and copolymerization with 2- hydroxyethyl methacrylate to obtain hydrogels showing composition-dependent swelling, degradation and mineralization. In the third part, two different types of bisphosphonate/ bisphosphonic acid functional thermoresponsive polymers were synthesized (i) by copolymerization of three novel bisphosphonate functionalized acrylamide monomers containing different alkyl chains with N-isopropyl acrylamide, (ii) alendronate functionalization of a copolymer of NIPAM and 6- acrylamidohexanoic acid. In the last part, alendronate was incorporated into two carboxylic acid containing polymers (ibuprofen functionalized alkyl α-hydroxymethacrylate and 6- acrylamidohexanoic acid based polymers) via covalent and non- covalent interactions to enhance their hydroxyapatite affinity. The materials synthesized here have potential for (mostly bone-related) biomedical applications such as tissue engineering and targeted controlled drug delivery; and the methods can be used to fabricate more such materials, tailoring their properties to fit the desired application.