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

Abstract

Two bisphosphonic acid-functionalized cross-linkers (one novel) with different spacer chain characteristics were synthesized and incorporated into hydrogels by copolymerization with 2-hydroxyethyl methacrylate at different ratios to control the hydrogels’ swelling, mechanical properties, and ability to support mineralization for biomedical applications. The cross-linkers were synthesized by reaction of 2-isocyanatoethyl methacrylate and bisphosphonated diamines followed by selective dealkylation of the bisphosphonate ester groups. The hydrogels provide in vitro growth of carbonated apatite, morphology affected by the cross-linker structure. The hydrogels exhibit a high Young’s modulus E (up to 400 kPa) and can sustain up to 10.2 ± 0.1 MPa compressive stresses. E and hence the cross-link density significantly increases upon mineralization reflecting the formation of many bisphosphonate BP–Ca 2+ bonds acting as additional cross-links. Cyclic mechanical tests reveal self-recoverability of hydrogels because of reversible nature of BP–Ca 2+ bonds. The results suggest that these cross-linkers can add calcium-binding abilities to hydrogels synthesized from any monomer and improve their mechanical, swelling, and mineralization properties and hence are potentially useful materials for biomedical applications.

Phosphonic acid‐functionalized poly(amido amine) macromers for biomedical applications

“…The interaction between phosphonic acid groups and Ca 2+ ions may form physical crosslinking. 18,19 However, it was observed that phosphonic acid content in the hydrogel needs to reach a certain level to This article is protected by copyright. All rights reserved.…”

“…13 It is well known that negatively charged groups such as the phosphate, (bis)phosphonate, carboxylate, sulfonic group on surfaces of hydrogels act as nucleating centers for the deposition of hydroxyapatite-like calcium phosphate and enhance mineralization which is a fundamental step for bone regenaration. [14][15][16][17][18][19][20] Additionally, phosphorous based groups promote cell adhesion and osteogenic differentiation. [21][22][23][24] Liu et al synthesized alendronate functionalized methacryloyl gelatin and observed upregulation of the osteogenesis-related genes as well as improvement in mineralization.…”

Platelet rich plasma–complexed hydrogel glue enhances skin wound healing in a diabetic rat model

“…Among various biomaterials, hydrogels that share many properties with soft tissue have become a research hotspot (Xue et al, 2019). Many types of hydrogels have been researched in dermal wound healing, such as bisphosphonate-functionalized hydrogel (Guven et al, 2018), chitosan hydrogel (Ponsubha and Jaiswal, 2020) and thermoresponsive hydrogel (Zhu et al, 2016). However, none of these materials allow for stable biological fixation, which is crucial in constructing the wound barrier and maintaining the applied agent (Dreifke et al, 2015).…”

Self Assemblies of Poly(ether ether ketone) Block Copolymers for Biomedical Applications

“…Phosphonate-chitosan functionalization of a multichannel hydroxyapatite scaffolds have been utilized for interfacial implant-bone tissue integration with the enhancement of new bone formation. [15] Further with phosphnated materials, the bioactive coatings consisting of phosphonated molecules and zirconia have been also designed for bone implants. [15] Although PEEK based polymers have been tried previously for dental and bone implants, however, modification of the PEEK chain can result in several issues such as non-uniform degree of modification and a compromise in the excellent properties of PEEK.…”

“…[15] Further with phosphnated materials, the bioactive coatings consisting of phosphonated molecules and zirconia have been also designed for bone implants. [15] Although PEEK based polymers have been tried previously for dental and bone implants, however, modification of the PEEK chain can result in several issues such as non-uniform degree of modification and a compromise in the excellent properties of PEEK. [8,9,10] Hence, modification of the PEEK backbone may not be as an effective tool to design a bioactive homopolymer as compared to its block copolymer counterpart.…”