Local pulsatile PTH delivery regenerates bone defects via enhanced bone remodeling in a cell-free scaffold

Parathyroid hormone (PTH) is currently the only FDA-approved anabolic drug to treat osteoporosis, and is systemically administered through daily injections. A new local pulsatile PTH delivery device was developed from biodegradable polymers to expand the application of PTH from systemic treatment to...

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Bibliographic Details
Published in:Biomaterials 2017-01, Vol.114, p.1-9
Main Authors: Dang, Ming, Koh, Amy J., Jin, Xiaobing, McCauley, Laurie K., Ma, Peter X.
Format: Article
Language:English
Subjects:
3D scaffold
Absorbable Implants
adverse effects
animal models
Animals
Biodegradability
biomimetics
Bone regeneration
Bone Regeneration - drug effects
Bone remodeling
Bones
Cell-free
Cell-Free System
Defects
Delayed-Action Preparations - administration & dosage
Delayed-Action Preparations - chemistry
Devices
Drug Implants - administration & dosage
Drug Implants - chemistry
drugs
Equipment Design
Guided Tissue Regeneration - instrumentation
Guided Tissue Regeneration - methods
Mice
Mice, Inbred C57BL
nanofibers
Nanofibers - chemistry
Nanofibers - ultrastructure
Nanostructure
osteoporosis
parathyroid hormone
Parathyroid Hormone - administration & dosage
polymers
PTH
Pulsatile release
Regeneration
Remodeling
Scaffolds
Skull Fractures - drug therapy
Skull Fractures - pathology
Tissue Scaffolds
Treatment Outcome
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Summary:Parathyroid hormone (PTH) is currently the only FDA-approved anabolic drug to treat osteoporosis, and is systemically administered through daily injections. A new local pulsatile PTH delivery device was developed from biodegradable polymers to expand the application of PTH from systemic treatment to spatially controlled local bone defect regeneration in this work. This is the first time that local pulsatile PTH delivery has been demonstrated to promote bone regeneration via enhanced bone remodeling. The biodegradable delivery device was designed to locally deliver PTH in a preprogrammed pulsatile manner. The PTH delivery was utilized to facilitate the regeneration of a bone defect spatially defined with a cell-free biomimetic nanofibrous (NF) scaffold. The local pulsatile PTH delivery (daily pulse for 21 days) not only promoted the regeneration of a critical-sized bone defect with negligible systemic side effects in a mouse model, but also advantageously achieved higher quality regenerated bone than the standard systemic PTH injection. These results demonstrate a promising and novel pulsatile PTH delivery device for spatially defined local bone regeneration.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2016.10.049