Craniofacial bone trauma and disease are widespread healthcare problems. Despite the significant healing capability of bone, the requirement for new bone to restore large osseous defects and defects in patients with various medical conditions is a major clinical challenge. Parathyroid hormone (PTH) is currently the only FDA approved anabolic agent to treat osteoporosis in the US, and holds strong promise for craniofacial bone regeneration. Our preliminary studies indicate that a systemic intermittent administration of PTH (daily injection) significantly stimulates bone regeneration in an engineered regenerative medicine model. However, there is no intermittent PTH delivery system available for local delivery applications and furthermore, the mechanisms of action of PTH to stimulate bone regeneration in an osseous wound healing model are unknown. We have developed polymers that enable an implantable prototype device for pulsatile PTH delivery as well as nanofibrous polymer/calcium phosphate composite scaffolds that enhance bone regeneration. Because one of the main functions of PTH is to regulate calcium levels and calcium is pro-proliferative for osteoblastic cells, we hypothesize that the anabolic activity of PTH depends on calcium availability. This proposed research will unite the expertise and resources of two experienced PIs and a Co-I to investigate the synergy between the PTH delivery and calcium availability in a biomimetic scaffold with translational potential for improve craniofacial bone regeneration. We will first develop both pulsatile and continuous PTH delivery systems, nanofibrous polymer/calcium phosphate composite scaffolds with varying calcium availability, and the optimal combination of the PTH delivery and calcium-containing scaffold. We will then investigate the mechanisms of the PTH action in relation to the calcium availability. Finally, based on these understandings we will regenerate craniofacial bone using the developed PTH delivery and scaffold technologies in a clinically relevant tooth extraction wound healing model.

Public Health Relevance

Parathyroid hormone (PTH) is currently used in humans to stimulate bone growth in patients with osteoporosis, and has been found to be beneficial in regenerating craniofacial bone. Unfortunately, the ability to deliver PTH locally has not been realized and its mechanisms of action are unclear which hinder clinical application. This project will investigate the mechanisms of action and applicability of using PTH to stimulate bone growth using a novel local delivery strategy. This innovation and information is critical in order o elucidate the clinical potential of PTH as a therapy to assist in oral bone healing.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Dentistry
Ann Arbor
United States
Zip Code
Kuang, Rong; Zhang, Zhanpeng; Jin, Xiaobing et al. (2016) Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp. Acta Biomater 33:225-34
Wang, Wei; Dang, Ming; Zhang, Zhanpeng et al. (2016) Dentin regeneration by stem cells of apical papilla on injectable nanofibrous microspheres and stimulated by controlled BMP-2 release. Acta Biomater 36:63-72
Al-Dujaili, Saja A; Koh, Amy J; Dang, Ming et al. (2016) Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone. J Cell Biochem 117:1556-67
Niu, Xufeng; Liu, Zhongning; Hu, Jiang et al. (2016) Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules. Macromol Biosci 16:1039-47
Zhang, Xiaojin; Li, Yan; Chen, Y Eugene et al. (2016) Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects. Nat Commun 7:10376
Dang, Ming; Koh, Amy J; Danciu, Theodora et al. (2016) Preprogrammed Long-Term Systemic Pulsatile Delivery of Parathyroid Hormone to Strengthen Bone. Adv Healthc Mater :
Guo, Baolin; Lei, Bo; Li, Peng et al. (2015) Functionalized scaffolds to enhance tissue regeneration. Regen Biomater 2:47-57
Hou, Sen; Ma, Peter X (2015) Stimuli-responsive supramolecular hydrogels with high extensibility and fast self-healing via precoordinated mussel-inspired chemistry. Chem Mater 27:7627-7635
Zhang, Zhanpeng; Marson, Ryan L; Ge, Zhishen et al. (2015) Simultaneous Nano- and Microscale Control of Nanofibrous Microspheres Self-Assembled from Star-Shaped Polymers. Adv Mater 27:3947-52
Rambhia, Kunal J; Ma, Peter X (2015) Controlled drug release for tissue engineering. J Control Release 219:119-28

Showing the most recent 10 out of 26 publications