Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen–nanodiamond hydrogel

Abstract

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, 17β-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-crosslinkable 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.nanomedicine | cleft palate | craniofacial medicine | nanodiamond | drug delivery

Novel Poly(Methyl Methacrylate) Containing Nanodiamond to Improve the Mechanical Properties and Fungal Resistance

“…Over the past decade, with advancement in manufacturing, the availability of nano derivatives of carbon such as nanodiamond has increased. NDs mimic the inherent superior physical properties of bulk diamond and have recently been demonstrated to be safe and biocompatible in multiple studies [45,46,47,48]. Therefore, the present study was designed to assess the improvements in the properties of poly(methyl methacrylate) on the addition of three different weight percentages of ND as nanofillers, with ZrO filler as the positive control.…”

The ERα/KDM6B regulatory axis modulates osteogenic differentiation in human mesenchymal stem cells

“…KDM6B is required for estrogen-mediated DMSC bone formation in vivo Our group previously reported the pro-osteogenic effects of estrogen delivery in an animal model of palatal fracture. 44 To assess the ability of estrogen to induce cell-mediated bone regeneration in a critical-sized defect, we generated calvarial defects with a 3 mm diameter in 8-week-old SCID mice, and Ap-PLGA scaffolds loaded with varying concentrations of E2 (1, 5, 25 μmol•L -1 ) were implanted following DMSC seeding. Micro-CT images demonstrated maximum bone formation at 25 μmol•L -1 E2 compared to the scaffold without E2 loading (Supplementary Fig.…”

Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel

“…Severe maxillary transverse deficiency (MTD) resulted from congenital malformation (e.g., cleft lip and/or palate) is one of the most pervasive maxillofacial malformation with high clinical demand [ [1] , [2] , [3] ]. Rapid maxillary expansion (RME), as the most regular treatment for MTD, has a high relapse rate of the expanded mid-palatal suture due to its inherent tendency of shape recovery and insufficient bone regenerative capability [ [4] , [5] , [6] , [7] ]. To avoid relapse, current treatments including excessive orthopedic expansion and long-term retainer wearing, mainly aim to resist the recovery tendency and have practical disadvantages and unsatisfactory therapeutic effects [ [8] , [9] , [10] ].…”