Bone regeneration in spaceflight: the effects of BMP and a novel bone regeneration agent in mice with bone defect exposed to microgravity

• Grant number: 15/25606-4
• Support Opportunities: Scholarships abroad - Research
• Start date: September 17, 2018
• End date: February 16, 2019
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Ariane Zamarioli
• Grantee: Ariane Zamarioli
• Host Investigator: Melissa Ann Kacena
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Indiana University-Purdue University Indianapolis, United States

Abstract

Segmental bone defects secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with segmental bone defects in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. There are many small animal investigations that have evaluated interventions for bone defects. While providing foundational information regarding treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. As an example, mice ambulate immediately following anesthetic recovery and in most cases are normally ambulating within 1-3 days post-surgery. Thus, to better test novel bone healing strategies there is a need to develop new models that combine disuse with bone healing. We have established collaboration with NASA to work in the ultimate disuse environment, microgravity (¼G). This proposal outlines an investigation to evaluate bone regeneration in mice with bone defects exposed to ¼G that have no treatment, are treated with BMP-2, or are treated with a novel bone regeneration agent, thrombopoietin (TPO). This will allow us to understand how bone regeneration occurs under conditions of accelerated bone loss and will allow us to determine whether non-weight bearing alters the therapeutic efficacy of BMP-2 or TPO. (AU)