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 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.
Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Ming
M
Dang
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
Amy J
AJ
Koh
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Xiaobing
X
Jin
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Laurie K
LK
McCauley
Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109-1078, USA; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA. Electronic address: mapx@umich.edu.
Peter X
PX
Ma
D020341:Absorbable Implants; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002474:Cell-Free System; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry; D004867:Equipment Design; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D012887:Skull Fractures / Q000188:drug therapy* / Q000473:pathology; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D004343:Drug Implants; D010281:Parathyroid Hormone
3D scaffold; Bone regeneration; Bone remodeling; Cell-free; PTH; Pulsatile release