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• W3090652278 endingPage "584" @default.
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• W3090652278 abstract "Abstract Purpose Although more than 18,000,000 fractures occur each year in the US, methods to promote fracture healing still rely primarily on fracture stabilization, with use of bone anabolic agents to accelerate fracture repair limited to rare occasions when the agent can be applied to the fracture surface. Because management of broken bones could be improved if bone anabolic agents could be continuously applied to a fracture over the entire course of the healing process, we undertook to identify strategies that would allow selective concentration of bone anabolic agents on a fracture surface following systemic administration. Moreover, because hydroxyapatite is uniquely exposed on a broken bone, we searched for molecules that would bind with high affinity and specificity for hydroxyapatite. We envisioned that by conjugating such osteotropic ligands to a bone anabolic agent, we could acquire the ability to continuously stimulate fracture healing. Results Although bisphosphonates and tetracyclines were capable of localizing small amounts of peptidic payloads to fracture surfaces 2-fold over healthy bone, their specificities and capacities for drug delivery were significantly inferior to subsequent other ligands, and were therefore considered no further. In contrast, short oligopeptides of acidic amino acids were found to localize a peptide payload to a bone fracture 91.9 times more than the control untargeted peptide payload. Furthermore acidic oligopeptides were observed to be capable of targeting all classes of peptides, including hydrophobic, neutral, cationic, anionic, short oligopeptides, and long polypeptides. We further found that highly specific bone fracture targeting of multiple peptidic cargoes can be achieved by subcutaneous injection of the construct. Conclusions Using similar constructs, we anticipate that healing of bone fractures in humans that have relied on immobilization alone can be greately enhanced by continuous stimulation of bone growth using systemic administration of fracture-targeted bone anabolic agents." @default.
• W3090652278 created "2020-10-08" @default.
• W3090652278 creator A5003507871 @default.
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• W3090652278 creator A5059670426 @default.
• W3090652278 creator A5068062942 @default.
• W3090652278 creator A5088752165 @default.
• W3090652278 date "2021-01-01" @default.
• W3090652278 modified "2023-10-16" @default.
• W3090652278 title "Analysis of the bone fracture targeting properties of osteotropic ligands" @default.
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• W3090652278 doi "https://doi.org/10.1016/j.jconrel.2020.09.047" @default.
• W3090652278 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33031877" @default.
• W3090652278 hasPublicationYear "2021" @default.
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