title: Preprogrammed Long-Term Systemic Pulsatile Delivery of Parathyroid Hormone to Strengthen Bone.
abstract: Parathyroid hormone (PTH) is the only US Food and Drug Administration (FDA)-approved anabolic agent for the treatment of osteoporosis. The anabolic action of PTH depends on the mode of PTH administration. Pulsatile administration promotes bone formation, however continuous PTH exposure results in bone resorption. In addition, the therapeutic effect of PTH is optimal when the dose and duration fit the therapeutic window. Current PTH treatment requires daily injection, which is neither a convenient nor a favorable choice of patients. Here, an implantable and biodegradable device capable of long-term pulsatile delivery of PTH is developed as a patient-friendly alternative. The advanced materials and fabrication techniques developed in this work enable us to preprogram a pulsatile delivery device to systemically deliver 21 daily pulses of PTH that build bone in vivo. In addition, the device is biodegradable and absorbable in vivo so that no retraction procedure is needed. Therefore, this implantable and biodegradable pulsatile device holds promise to promote bone growth and treat various conditions of bone loss without the burden of daily injections or secondary surgeries.
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Dang
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Koh
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
authors.forename: Theodora
authors.initials: T
authors.lastname: Danciu
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.|Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Materials Science and Engineering, The University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004343:Drug Implants; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004343:Drug Implants; D010281:Parathyroid Hormone
keywords: PTH delivery; biodegradable device; bone; long-term pulsatile release