Hydrogel-Based Local Release of Salubrinal Stimulates Healing of Mouse Tibia FractureWenxiao Xu1,2, Andy Chen3, Yijia Zhang1, Jiliang Li4, Chien-Chi Lin1, Jing-long Yan2 and Hiroki Yokota1*
- *Corresponding Author:
- Hiroki Yokota
Department of Biomedical Engineering
Indiana University Purdue University Indianapolis
723 West Michigan Street, SL220
Indianapolis, IN 46202, USA
E-mail: [email protected]
Received Date: June 10, 2016; Accepted Date: July 01, 2016; Published Date: July 08, 2016
Citation: Xu W, Chen A, Zhang Y, Li J, Lin CC, et al. (2016) Hydrogel-Based Local Release of Salubrinal Stimulates Healing of Mouse Tibia Fracture. Orthop Muscular Syst 5:220. doi:10.4172/2161-0533.1000220
Copyright: © 2016 Xu W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Background: Salubrinal is a small synthetic agent that presents beneficial effects on skeletal diseases and tumor progression. It is reported to stimulate bone formation and suppress bone resorption. In this study, we examined whether salubrinal administration can stimulate the healing of bone fracture using a mouse model of closed tibia fracture.
Materials and Methods: We administered salubrinal to mice in two different routes: one-time hydrogel injection with salubrinal-loaded Poly Lactic-Co-Glycolic Acid (PLGA) microparticles; and daily subcutaneous injection for 4 weeks. A subcutaneous injection of Bone Morphogenetic Protein 2 (BMP2) was used as a positive control. The measurement of Bone Mineral Density (BMD)/Bone Mineral Content (BMC), as well as micro-CT imaging and mechanical testing were utilized to evaluate the healing of the experimental fracture.
Results: It was shown that 4 weeks after the induction of tibia fracture no groups, including the BMP2 control group, elevated BMD or BMC. Hydrogel-based injection of salubrinal showed a higher stiffness than that of the vehicle control, as well as significant elevation of ultimate force. Although daily subcutaneous injection of BMP2 increased stiffness and ultimate force, daily injection of salubrinal did not show significant improvement of mechanical properties. Of note, the total salubrinal dose in the hydrogel group was approximately 18% of that in the subcutaneous group.
Discussion: Improvement in mechanical properties by a hydrogel-based administration of salubrinal and not by a daily subcutaneous injection indicates dependence of salubrinal’s efficacy on its administration procedure. Salubrinal is capable of suppressing tumor growth, a clear advantage over a growth factor such as BMP2. For a future clinical trial, administration frequency and optimal dosage may need to be further analyzed.