Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 35, Pages E7218-E7225Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1704027114
Keywords
nanomedicine; cleft palate; craniofacial medicine; nanodiamond; drug delivery
Categories
Funding
- American Association of Orthodontists Foundation Biomedical Research Award
- National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR) K08 Award [K08DE024603]
- National Science Foundation CAREER Award [CMMI-1350197]
- Center for Scalable and Integrated NanoManufacturing [DMI-0327077, CMMI-0856492, DMR-1343991, OISE-1444100]
- V Foundation for Cancer Research Scholars Award
- Wallace H. Coulter Foundation Translational Research Award
- National Cancer Institute Grant [U54CA151880]
- Society for Laboratory Automation and Screening Endowed Fellowship
- Beckman Coulter Life Sciences
- American Academy of Implant Dentistry Research Foundation [20150460]
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Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17 beta-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.
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