Abstract
Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function. As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. To date, both biomolecule-clay and polymer-clay nanocomposite strategies have utilised the negatively charged clay particle surface. As such, biomolecule-clay and polymer-clay interactions are set in competition, potentially limiting the functional enhancements achieved. Here, we apply specific bisphosphonate interactions with the positively charged clay particle edge to develop self-assembling hydrogels and functionalized clay nanoparticles with preserved surface exchange capacity. Low concentrations of nanoclay are applied to cross-link hyaluronic acid polymers derivatised with a pendant bisphosphonate to generate hydrogels with enhanced mechanical properties and preserved protein binding able to sustain, for over six weeks in vivo, the localized activity of the clinically licensed growth factor BMP-2.
Highlights
Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function
Nanoclay–protein complexes allow localized activity of bioactive molecules within a hydrogel environment permissive for cellular ingress. This approach has been applied to achieve high loading and localized delivery of insulin-like growth factor-1 mimetic protein[5], localization of vascular endothelial growth factor to initiate the formation of new blood vessels at an injury site[6,7], and localization of bone morphogenetic protein (BMP)-2 to achieve ectopic bone formation at the lowest dose recorded in the literature to date[8]
Laponite addition to chemically crosslinked HABP gels led to only a 3-fold increase in modulus (Fig. 2a) indicating interference of the slow forming BP-Laponite coordination by chemical crosslinking and confirming the enhancements conferred by utilizing nanoclay as a cross-linker (Fig. 2b)
Summary
Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. On the other hand, where polymer–clay nanocomposites have been optimized for their mechanical properties, any influence of clay on the drug release profile is often minimal and secondary to the clay’s primary influence on the polymeric network (e.g., through reduced swelling or degradation)[9,12] This competitive compromise between strategies can be explained, at least in part, by the fact that both applications classically seek to employ the same site of interaction: the negatively charged surface of the clay particle. Tetravalent pyrophosphate salts are applied commercially to inhibit aggregation and improve dispersion by complexing with, and screening, the hydroxyl groups exposed at the particle edge[13,14,15]
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