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

Ming Dang; Amy J Koh; Xiaobing Jin; Laurie K McCauley; Peter X Ma

doi:10.1016/j.biomaterials.2016.10.049

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

Biomaterials. 2017 Jan:114:1-9. doi: 10.1016/j.biomaterials.2016.10.049. Epub 2016 Nov 1.

Authors

Ming Dang¹, Amy J Koh², Xiaobing Jin³, Laurie K McCauley⁴, Peter X Ma⁵

Affiliations

¹ Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109-1078, USA.
² Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
³ Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA.
⁴ 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.
⁵ 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.

Abstract

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.

Keywords: 3D scaffold; Bone regeneration; Bone remodeling; Cell-free; PTH; Pulsatile release.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Absorbable Implants
Animals
Bone Regeneration / drug effects*
Cell-Free System
Delayed-Action Preparations / administration & dosage*
Delayed-Action Preparations / chemistry
Drug Implants / administration & dosage*
Drug Implants / chemistry
Equipment Design
Guided Tissue Regeneration / instrumentation
Guided Tissue Regeneration / methods
Mice
Mice, Inbred C57BL
Nanofibers / chemistry*
Nanofibers / ultrastructure
Parathyroid Hormone / administration & dosage*
Skull Fractures / drug therapy*
Skull Fractures / pathology
Tissue Scaffolds*
Treatment Outcome

Substances

Delayed-Action Preparations
Drug Implants
Parathyroid Hormone

Abstract

Publication types

MeSH terms

Substances

Grants and funding